Human papillomavirus infection#Signs and symptoms

HPV is a group of more than 200 related viruses, which are designated by a number for each virus type.{{Cite web |date=18 October 2023 |title=HPV and Cancer - National Cancer Institute |url=https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-and-cancer |access-date=18 January 2024 |website=National Cancer Institute |language=en}} Some HPV types, such as HPV5, may establish infections that persist for the lifetime of the individual without ever manifesting any clinical symptoms. HPV types 1 and 2 can cause common warts in some infected individuals.{{cite web |last1=M. Al Aboud |first1=Ahmad |last2=Nigam |first2=Pramod K. | title=Wart (Plantar, Verruca Vulgaris, Verrucae) |year=2022 |url=https://www.ncbi.nlm.nih.gov/books/NBK431047/ |publisher=Stat Pearls |pmid=28613701 |access-date=4 December 2019}} HPV types 6 and 11 can cause genital warts and laryngeal papillomatosis.

Many HPV types are carcinogenic.{{cite journal | vauthors = Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, Snijders PJ, Meijer CJ | title = Epidemiologic classification of human papillomavirus types associated with cervical cancer | journal = The New England Journal of Medicine | volume = 348 | issue = 6 | pages = 518–27 | date = February 2003 | pmid = 12571259 | doi = 10.1056/NEJMoa021641 | collaboration = International Agency for Research on Cancer Multicenter Cervical Cancer Study Group | hdl = 2445/122831 | s2cid = 1451343 | url = https://revistasojs.ucaldas.edu.co/index.php/hacialapromociondelasalud/article/view/2173 | hdl-access = free }} About twelve HPV types (including types 16, 18, 31, and 45) are called "high-risk" types because persistent infection has been linked to cancer of the oropharynx, larynx, vulva, vagina, cervix, penis, and anus.{{cite journal | vauthors = Nowińska K, Ciesielska U, Podhorska-Okołów M, Dzięgiel P | title = The role of human papillomavirus in oncogenic transformation and its contribution to the etiology of precancerous lesions and cancer of the larynx: A review | journal = Advances in Clinical and Experimental Medicine | volume = 26 | issue = 3 | pages = 539–547 | date = 2017 | pmid = 28791831 | doi = 10.17219/acem/67461 | doi-access = free }} These cancers all involve sexually transmitted infection of HPV to the stratified epithelial tissue. HPV type 16 is the strain most likely to cause cancer and is present in about 47% of all cervical cancers,{{cite journal | vauthors = Noel J, Lespagnard L, Fayt I, Verhest A, Dargent J | title = Evidence of human papilloma virus infection but lack of Epstein-Barr virus in lymphoepithelioma-like carcinoma of uterine cervix: report of two cases and review of the literature | journal = Human Pathology | volume = 32 | issue = 1 | pages = 135–8 | date = January 2001 | pmid = 11172309 | doi = 10.1053/hupa.2001.20901 }} and in many vaginal and vulvar cancers,{{cite web|url=http://nurse-practitioners.advanceweb.com/Article/Vulvar-Intraepithelial-Neoplasia.aspx|title=Vulvar Intraepithelial Neoplasia: Varied signs, varied symptoms: what you need to know|publisher=www.advanceweb.com|archive-url=https://archive.today/20120716205333/http://nurse-practitioners.advanceweb.com/Article/Vulvar-Intraepithelial-Neoplasia.aspx|archive-date=16 July 2012|access-date=5 August 2009}} penile cancers, anal cancers, and cancers of the head and neck.

The table below lists common symptoms of HPV infection and the associated types of HPV.

Available HPV vaccines protect against either two, four, or nine types of HPV.{{cite journal | vauthors = ((World Health Organization)) | title = Human papillomavirus vaccines: WHO position paper (2022 update) | journal = Weekly Epidemiological Record | volume = 97 | issue = 50 | pages = 645–672 | date = December 2022 | hdl = 10665/365351 | author-link = World Health Organization | hdl-access = free }} There are six prophylactic HPV vaccines licensed for use: the bivalent vaccines Cervarix, Cecolin, and Walrinvax; the quadrivalent vaccines Cervavax and Gardasil; and the nonavalent vaccine Gardasil 9. All HPV vaccines protect against at least HPV types 16 and 18, which cause the greatest risk of cervical cancer. The quadrivalent vaccines also protect against HPV types 6 and 11. The nonavalent vaccine Gardasil 9 protects against those four types (6, 11, 16, and 18), along with five other high-risk HPV types responsible for 20% of cervical cancers (types 31, 33, 45, 52, and 58).

{{Anchor |Diseases associated with HPV}}

Image:Papilloma.jpg

Image:Sample HPV-6 Histology Report for Throat Warts (Papiloma).jpg

Skin infection ("cutaneous" infection) with HPV is very widespread.{{cite journal | vauthors = Antonsson A, Forslund O, Ekberg H, Sterner G, Hansson BG | title = The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses | journal = Journal of Virology | volume = 74 | issue = 24 | pages = 11636–41 | date = December 2000 | pmid = 11090162 | pmc = 112445 | doi = 10.1128/JVI.74.24.11636-11641.2000 }}

Skin infections with HPV can cause noncancerous skin growths called warts (verrucae). Warts are caused by the rapid growth of cells on the outer layer of the skin.Mayo Clinic.com, Common warts, http://www.mayoclinic.com/print/common-warts/DS00370/ {{webarchive|url=https://web.archive.org/web/20111017103048/http://www.mayoclinic.com/print/common-warts/DS00370/DSECTION%3Dall%26METHOD%3Dprint |date=17 October 2011 }}

While cases of warts have been described since the time of ancient Greece, their viral cause was not known until 1907.

Skin warts are most common in childhood and typically appear and regress spontaneously over weeks to months. Recurring skin warts are common.{{Cite book|last1=Al Aboud|first1=Ahmad M.|last2=Nigam|first2=Pramod K. |url=https://www.ncbi.nlm.nih.gov/books/NBK431047/|chapter=Wart|title=StatPearls|date=11 August 2020|publisher=StatPearls Publishing|location=Treasure Island (FL)|pmid=28613701 }} All HPVs are believed to be capable of establishing long-term "latent" infections in small numbers of stem cells present in the skin. Although these latent infections may never be fully eradicated, immunological control is thought to block the appearance of symptoms such as warts. Immunological control is HPV type-specific, meaning an individual may become resistant to one HPV type while remaining susceptible to other types.{{citation needed|date=May 2021}}

Types of warts include:

• Common warts are usually found on the hands and feet, but can also occur in other areas, such as the elbows or knees. Common warts have a characteristic cauliflower-like surface and are typically slightly raised above the surrounding skin. Cutaneous HPV types can cause genital warts but are not associated with the development of cancer.{{citation needed|date=November 2022}}
• Plantar warts are found on the soles of the feet; they grow inward, generally causing pain when walking.
• Subungual or periungual warts form under the fingernail (subungual), around the fingernail, or on the cuticle (periungual). They are more difficult to treat than warts in other locations.{{cite journal | vauthors = Lountzis NI, Rahman O | title = Images in clinical medicine. Digital verrucae | journal = The New England Journal of Medicine | volume = 359 | issue = 2 | page = 177 | date = July 2008 | pmid = 18614785 | doi = 10.1056/NEJMicm071912 }}
• Flat warts are most commonly found on the arms, face, or forehead. Like common warts, flat warts occur most frequently in children and teens. In people with normal immune function, flat warts are not associated with the development of cancer.MedlinePlus, Warts, https://www.nlm.nih.gov/medlineplus/warts.html#cat42 {{webarchive|url=https://web.archive.org/web/20160605063307/https://www.nlm.nih.gov/medlineplus/warts.html |date=5 June 2016 }} (general reference with links). Also, see

Common, flat, and plantar warts are much less likely to spread from person to person.

HPV infection of the skin in the genital area is the most common sexually transmitted infection worldwide.{{cite book|title=World Cancer Report 2014|date=2014|publisher=World Health Organization|isbn=978-92-832-0429-9|pages=Chapter 5.12}} Such infections are associated with genital or anal warts (medically known as condylomata acuminata or venereal warts), and these warts are the most easily recognized sign of genital HPV infection.{{citation needed|date=May 2021}}

The strains of HPV that can cause genital warts are usually different from those that cause warts on other parts of the body, such as the hands or feet, or even the inner thighs. A wide variety of HPV types can cause genital warts, but types 6 and 11 together account for about 90% of all cases.{{cite journal | vauthors = Greer CE, Wheeler CM, Ladner MB, Beutner K, Coyne MY, Liang H, Langenberg A, Yen TS, Ralston R | title = Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts | journal = Journal of Clinical Microbiology | volume = 33 | issue = 8 | pages = 2058–63 | date = August 1995 | pmid = 7559948 | pmc = 228335 | doi = 10.1128/jcm.33.8.2058-2063.1995 }} However, in total more than 40 types of HPV are transmitted through sexual contact and can infect the skin of the anus and genitals. Such infections may cause genital warts, although they may also remain asymptomatic.{{citation needed|date=May 2021}}

The great majority of genital HPV infections never cause any overt symptoms and are cleared by the immune system in a matter of months. Moreover, people may transmit the virus to others even if they do not display overt symptoms of infection. Most people acquire genital HPV infections at some point in their lives, and about 10% of women are currently infected. A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity. As with cutaneous HPVs, immunity to genital HPV is believed to be specific to a specific strain of HPV.{{citation needed|date=May 2021}}

In addition to genital warts, infection by HPV types 6 and 11 can cause a rare condition known as recurrent laryngeal papillomatosis, in which warts form on the larynx{{cite web |url=http://www.voicemedicine.com/papilloma.htm |title=Photos of larynx Papillomas — Voice Medicine, New York |publisher=Voicemedicine.com |access-date=29 August 2010 |archive-url=https://web.archive.org/web/20100612162015/http://www.voicemedicine.com/papilloma.htm |archive-date=12 June 2010 }} or other areas of the respiratory tract.{{cite journal | vauthors = Sinal SH, Woods CR | title = Human papillomavirus infections of the genital and respiratory tracts in young children | journal = Seminars in Pediatric Infectious Diseases | volume = 16 | issue = 4 | pages = 306–16 | date = October 2005 | pmid = 16210110 | doi = 10.1053/j.spid.2005.06.010 }}{{cite journal | vauthors = Wu R, Sun S, Steinberg BM | title = Requirement of STAT3 activation for differentiation of mucosal stratified squamous epithelium | journal = Molecular Medicine | volume = 9 | issue = 3–4 | pages = 77–84 | year = 2003 | pmid = 12865943 | pmc = 1430729 | doi = 10.2119/2003-00001.Wu }}

These warts can recur frequently, may interfere with breathing, and in extremely rare cases can progress to cancer. For these reasons, repeated surgery to remove the warts may be advisable.{{cite journal | vauthors = Moore CE, Wiatrak BJ, McClatchey KD, Koopmann CF, Thomas GR, Bradford CR, Carey TE | title = High-risk human papillomavirus types and squamous cell carcinoma in patients with respiratory papillomas | journal = Otolaryngology–Head and Neck Surgery | volume = 120 | issue = 5 | pages = 698–705 | date = May 1999 | pmid = 10229596 | doi = 10.1053/hn.1999.v120.a91773 | s2cid = 6560398 }}

Cervical cancer is among the most common cancers worldwide, causing an estimated 604,000 new cases and 342,000 deaths in 2020.{{Cite web |date=22 February 2022 |title=Human papillomavirus (HPV) and cervical cancer - WHO |url=https://www.who.int/news-room/fact-sheets/detail/cervical-cancer |url-status=live |archive-url=https://web.archive.org/web/20230422212009/http://www.who.int/News-Room/Fact-Sheets/Detail/Cervical-Cancer |archive-date=22 April 2023 |website=World Health Organization}} About 90% of these new cases and deaths of cervical cancer occurred in low- and middle-income countries, where screening tests and treatment of early cervical cell changes are not readily available. In the USA, cervical cancer accounts for 0.7% of new cancer cases.{{cite web |title=Cancer Stat Facts: Cervical Cancer |url=https://seer.cancer.gov/statfacts/html/cervix.html |website=National Cancer Institute SEER statistics |publisher=National Cancer Institute |access-date=22 June 2025}} Oral cavity and pharynx cancer accounts for 2.9% of new cases in the USA and predominently affects men.{{cite web |title=Cancer Stat Facts: Oral Cavity and Pharynx Cancer |url=https://seer.cancer.gov/statfacts/html/oralcav.html |website=National Cancer Institute SEER statistics |publisher=National Cancer Institute |access-date=22 June 2025}} HPV is thought to cause 60% to 70% of oropharyngeal cancers in the United States.{{cite web |title=HPV and Oropharyngeal Cancer |url=https://www.cdc.gov/cancer/hpv/oropharyngeal-cancer.html |website=US Centers for Disease Control |date=17 September 2024 |access-date=22 June 2025}}

In the United States, about 37,300 cases of cancer due to HPV occur each year.

Image:HPV-16 genome organization.png

In some infected individuals, their immune systems may fail to control HPV. Lingering infection with high-risk HPV types, such as types 16, 18, 31, and 45, can favor the development of cancer.{{cite journal | vauthors = Schiffman M, Castle PE | title = The promise of global cervical-cancer prevention | journal = The New England Journal of Medicine | volume = 353 | issue = 20 | pages = 2101–4 | date = November 2005 | pmid = 16291978 | doi = 10.1056/NEJMp058171 | doi-access = free }}

Co-factors such as cigarette smoke can also enhance the risk of HPV-related cancers.{{cite journal | vauthors = Alam S, Conway MJ, Chen HS, Meyers C | title = The cigarette smoke carcinogen benzo[a]pyrene enhances human papillomavirus synthesis | journal = Journal of Virology | volume = 82 | issue = 2 | pages = 1053–8 | date = January 2008 | pmid = 17989183 | pmc = 2224590 | doi = 10.1128/JVI.01813-07 }}{{cite journal | vauthors = Lu B, Hagensee ME, Lee JH, Wu Y, Stockwell HG, Nielson CM, Abrahamsen M, Papenfuss M, Harris RB, Giuliano AR | title = Epidemiologic factors associated with seropositivity to human papillomavirus type 16 and 18 virus-like particles and risk of subsequent infection in men | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 19 | issue = 2 | pages = 511–6 | date = February 2010 | pmid = 20086109 | doi = 10.1158/1055-9965.EPI-09-0790 | s2cid = 22440577 | doi-access = free }}

HPV is believed to cause cancer by integrating its genome into nuclear DNA. Some of the early genes expressed by HPV, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation. HPV genome integration can also cause carcinogenesis by promoting genomic instability associated with alterations in DNA copy number.{{cite journal | vauthors = Parfenov M, Pedamallu CS, Gehlenborg N, Freeman SS, Danilova L, Bristow CA, Lee S, Hadjipanayis AG, Ivanova EV, Wilkerson MD, Protopopov A, Yang L, Seth S, Song X, Tang J, Ren X, Zhang J, Pantazi A, Santoso N, Xu AW, Mahadeshwar H, Wheeler DA, Haddad RI, Jung J, Ojesina AI, Issaeva N, Yarbrough WG, Hayes DN, Grandis JR, El-Naggar AK, Meyerson M, Park PJ, Chin L, Seidman JG, Hammerman PS, Kucherlapati R | title = Characterization of HPV and host genome interactions in primary head and neck cancers | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 43 | pages = 15544–9 | date = October 2014 | pmid = 25313082 | pmc = 4217452 | doi = 10.1073/pnas.1416074111 | bibcode = 2014PNAS..11115544P | doi-access = free }}

E6 produces a protein (also called E6) that simultaneously binds to two host cell proteins called p53 and E6-Associated Protein (E6-AP). E6AP is an E3 Ubiquitin ligase, an enzyme whose purpose is to tag proteins with a post-translational modification called Ubiquitin. By binding both proteins, E6 induces E6AP to attach a chain of ubiquitin molecules to p53, thereby flagging p53 for proteosomal degradation.{{Cite journal |last1=Scheffner |first1=Martin |last2=Huibregtse |first2=Jon M. |last3=Vierstra |first3=Richard D. |last4=Howley |first4=Peter M. |date=November 1993 |title=The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53 |url=https://linkinghub.elsevier.com/retrieve/pii/0092867493903843 |journal=Cell |language=en |volume=75 |issue=3 |pages=495–505 |doi=10.1016/0092-8674(93)90384-3|pmid=8221889 |s2cid=27437768 |url-access=subscription }}{{Cite journal |last1=Zanier |first1=Katia |last2=Charbonnier |first2=Sebastian |last3=Sidi |first3=Abdellahi Ould M'hamed Ould |last4=McEwen |first4=Alastair G. |last5=Ferrario |first5=Maria Giovanna |last6=Poussin-Courmontagne |first6=Pierre |last7=Cura |first7=Vincent |last8=Brimer |first8=Nicole |last9=Babah |first9=Khaled Ould |last10=Ansari |first10=Tina |last11=Muller |first11=Isabelle |date=8 February 2013 |title=Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins |journal=Science |volume=339 |issue=6120 |pages=694–698 |doi=10.1126/science.1229934 |issn=1095-9203 |pmc=3899395 |pmid=23393263|bibcode=2013Sci...339..694Z }} Normally, p53 acts to prevent cell growth and promotes cell death in the presence of DNA damage. p53 also upregulates the p21 protein, which blocks the formation of the cyclin D/Cdk4 complex, thereby preventing the phosphorylation of retinoblastoma protein (RB), and in turn, halting cell cycle progression by preventing the activation of E2F. In short, p53 is a tumor-suppressor protein that arrests the cell cycle and prevents cell growth and survival when DNA damage occurs.{{Cite journal |last1=Hafner |first1=Antonina |last2=Bulyk |first2=Martha L. |last3=Jambhekar |first3=Ashwini |last4=Lahav |first4=Galit |date=April 2019 |title=The multiple mechanisms that regulate p53 activity and cell fate |journal=Nature Reviews. Molecular Cell Biology |volume=20 |issue=4 |pages=199–210 |doi=10.1038/s41580-019-0110-x |issn=1471-0080 |pmid=30824861|s2cid=71143679 }} Thus, the degradation of p53, induced by E6, promotes unregulated cell division, cell growth, and cell survival, all characteristics of cancer.{{Cite journal |last1=Hanahan |first1=Douglas |last2=Weinberg |first2=Robert A. |date=7 January 2000 |title=The Hallmarks of Cancer |journal=Cell |language=English |volume=100 |issue=1 |pages=57–70 |doi=10.1016/S0092-8674(00)81683-9 |issn=0092-8674 |pmid=10647931 |s2cid=1478778 |doi-access=free}}

It is important to note that while the interaction between E6, E6AP, and p53 was the first to be characterized, there are multiple other proteins in the host cell that interact with E6 and assist in the induction of cancer.{{Cite journal |last1=Tungteakkhun |first1=Sandy S. |last2=Duerksen-Hughes |first2=Penelope J. |date=2008 |title=Cellular binding partners of the human papillomavirus E6 protein |journal=Archives of Virology |volume=153 |issue=3 |pages=397–408 |doi=10.1007/s00705-007-0022-5 |issn=0304-8608 |pmc=2249614 |pmid=18172569}}

Studies have also shown a link between a wide range of HPV types and squamous cell carcinoma of the skin. In such cases, in vitro studies suggest that the E6 protein of the HPV virus may inhibit apoptosis induced by ultraviolet light.{{cite journal | vauthors = Karagas MR, Waterboer T, Li Z, Nelson HH, Michael KM, Bavinck JN, Perry AE, Spencer SK, Daling J, Green AC, Pawlita M | title = Genus beta human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study | journal = BMJ | volume = 341 | pages = c2986 | date = July 2010 | pmid = 20616098 | pmc = 2900549 | doi = 10.1136/bmj.c2986 }}

File:HPV causing cervical cancer.jpg

Nearly all cases of cervical cancer are associated with HPV infection, with two types, HPV16 and HPV18, present in 70% of cases.{{cite journal | vauthors = Cohen J | title = Public health. High hopes and dilemmas for a cervical cancer vaccine | journal = Science | volume = 308 | issue = 5722 | pages = 618–21 | date = April 2005 | pmid = 15860602 | doi = 10.1126/science.308.5722.618 | s2cid = 31712160 }}{{cite journal | vauthors = Ault KA | title = Epidemiology and natural history of human papillomavirus infections in the female genital tract | journal = Infectious Diseases in Obstetrics and Gynecology | volume = 2006 Suppl | page = 40470 | year = 2006 | pmid = 16967912 | pmc = 1581465 | doi = 10.1155/IDOG/2006/40470 | doi-access = free }}{{cite journal | vauthors = Kreimer AR, Clifford GM, Boyle P, Franceschi S | title = Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 14 | issue = 2 | pages = 467–75 | date = February 2005 | pmid = 15734974 | doi = 10.1158/1055-9965.EPI-04-0551 | s2cid = 6643303 | doi-access = free }} In 2012, twelve HPV types were considered carcinogenic for cervical cancer by the International Agency for Research on Cancer: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59.{{cite journal |vauthors=Arbyn, Tommasino, Depuydt, Dillner |date=15 August 2014 |title=Are 20 human papillomavirus types causing cervical cancer? |journal=The Journal of Pathology |volume=234 |issue=4 |pages=431–435 |doi=10.1002/path.4424|pmid=25124771 |s2cid=7775411 |doi-access=free }} One study found that 74% of squamous cell carcinomas and 78% of adenocarcinomas tested positive for HPV types 16 or 18.{{cite journal | vauthors = Berrington de González A, Green J | title = Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies | journal = International Journal of Cancer | volume = 120 | issue = 4 | pages = 885–91 | date = February 2007 | pmid = 17131323 | doi = 10.1002/ijc.22357 | s2cid = 33495556 | collaboration = International Collaboration of Epidemiological Studies of Cervical Cancer | doi-access = free }} Persistent HPV infection increases the risk for developing cervical carcinoma. Individuals who have an increased incidence of these types of infection are women with HIV/AIDS, who are at a 22-fold increased risk of cervical cancer.{{cite journal | vauthors = Denny LA, Franceschi S, de Sanjosé S, Heard I, Moscicki AB, Palefsky J | title = Human papillomavirus, human immunodeficiency virus and immunosuppression | journal = Vaccine | volume = 30 | pages = F168-74 | date = November 2012 | issue = Suppl 5 | pmid = 23199960 | doi = 10.1016/j.vaccine.2012.06.045 | url = https://zenodo.org/record/3443736 | access-date = 28 November 2019 | archive-url = https://web.archive.org/web/20191108031115/https://zenodo.org/record/3443736 | archive-date = 8 November 2019 }}{{cite journal | vauthors = Dugué PA, Rebolj M, Garred P, Lynge E | title = Immunosuppression and risk of cervical cancer | journal = Expert Review of Anticancer Therapy | volume = 13 | issue = 1 | pages = 29–42 | date = January 2013 | pmid = 23259425 | doi = 10.1586/era.12.159| s2cid = 26312718 }}

The carcinogenic HPV types in cervical cancer belong to the alphapapillomavirus genus and can be grouped further into HPV clades.{{Cite journal|last1=Willemsen|first1=Anouk|last2=Bravo|first2=Ignacio G.|date=27 September 2018|title=Origin and evolution of papillomavirus (onco)genes and genomes|url= |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=374|issue=1773|doi=10.1098/rstb.2018.0303|biorxiv=10.1101/428912|pmid=30955499|pmc=6501903}} The two major carcinogenic HPV clades, alphapapillomavirus-9 (A9) and alphapapillomavirus-7 (A7), contain HPV16 and HPV18, respectively.{{Cite journal|last1=Doorbar|first1=John|last2=Quint|first2=Wim|last3=Banks|first3=Lawrence|last4=Bravo|first4=Ignacio G.|last5=Stoler|first5=Mark|last6=Broker|first6=Tom R.|last7=Stanley|first7=Margaret A.|date=November 2012|title=The Biology and Life-Cycle of Human Papillomaviruses|journal=Vaccine|volume=30|pages=F55–F70|doi=10.1016/j.vaccine.2012.06.083|pmid=23199966|issn=0264-410X|doi-access=free}} These two HPV clades were shown to have different effects on tumour molecular characteristics and patient prognosis, with clade A7 being associated with more aggressive pathways and an inferior prognosis.{{Cite journal|last1=Gagliardi|first1=Alessia|last2=Porter|first2=Vanessa L.|last3=Zong|first3=Zusheng|last4=Bowlby|first4=Reanne|last5=Titmuss|first5=Emma|last6=Namirembe|first6=Constance|last7=Griner|first7=Nicholas B.|last8=Petrello|first8=Hilary|last9=Bowen|first9=Jay|last10=Chan|first10=Simon K.|last11=Culibrk|first11=Luka|date=August 2020|title=Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade–specific epigenome and transcriptome landscapes|url= |journal=Nature Genetics|volume=52|issue=8|pages=800–810|doi=10.1038/s41588-020-0673-7|pmid=32747824|pmc=7498180|issn=1061-4036}}

In 2020, about 604,000 new cases and 342,000 deaths from cervical cancer occurred worldwide. Around 90% of these occurred in the developing world.

Most HPV infections of the cervix are cleared rapidly by the immune system and do not progress to cervical cancer (see below the Clearance subsection in Virology). Because the process of transforming normal cervical cells into cancerous ones is slow, cancer occurs in people who have been infected with HPV for a long time, usually over a decade or more (persistent infection).{{cite journal | vauthors = Greenblatt RJ | title = Human papillomaviruses: Diseases, diagnosis, and a possible vaccine | journal = Clinical Microbiology Newsletter | volume = 27 | issue = 18 | pages = 139–145 | year = 2005 | doi = 10.1016/j.clinmicnews.2005.09.001 }} Furthermore, both the HPV infection and cervical cancer drive metabolic modifications that may be correlated with the aberrant regulation of enzymes related to metabolic pathways.{{Cite journal |doi=10.17305/bjbms.2019.4359 |pmc=7029203 |pmid=31465717 |doi-access=free|title=Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection |year=2019 |last1=Abudula |first1=Abulizi |last2=Rouzi |first2=Nuermanguli |last3=Xu |first3=Lixiu |last4=Yang |first4=Yun |last5=Hasimu |first5=Axiangu |journal=Bosnian Journal of Basic Medical Sciences |volume=20 |issue=1 |pages=78–87 }}

Non-European (NE) HPV16 variants are significantly more carcinogenic than European (E) HPV16 variants.{{cite journal | vauthors = Freitas LB, Chen Z, Muqui EF, Boldrini NA, Miranda AE, Spano LC, Burk RD | title = Human papillomavirus 16 non-European variants are preferentially associated with high-grade cervical lesions | journal = PLOS ONE | volume = 9 | issue = 7 | pages = e100746 | date = 1 July 2014 | pmid = 24983739 | pmc = 4077691 | doi = 10.1371/journal.pone.0100746 | bibcode = 2014PLoSO...9j0746F | doi-access = free }}

The risk for anal cancer is 17 to 31 times higher among HIV-positive individuals who were coinfected with high-risk HPV, and 80 times higher for particularly HIV-positive men who have sex with men.{{cite journal | vauthors = Burd EM, Dean CL | title = Human Papillomavirus | journal = Microbiology Spectrum | volume = 4 | issue = 4 | pages = 177–195 | date = August 2016 | pmid = 27726787 | doi = 10.1128/microbiolspec.dmih2-0001-2015 | publisher = American Society of Microbiology | isbn = 978-1-55581-903-3 | veditors = Hayden RT, Wolk DM, Carroll KC, Tang YC | series = Diagnostic Microbiology of the Immunocompromised Host | edition = Second | doi-access = free }}

Anal Pap smear screening for anal cancer might benefit some subpopulations of men or women engaging in anal sex.{{cite journal | vauthors = Chin-Hong PV, Vittinghoff E, Cranston RD, Browne L, Buchbinder S, Colfax G, Da Costa M, Darragh T, Benet DJ, Judson F, Koblin B, Mayer KH, Palefsky JM | title = Age-related prevalence of anal cancer precursors in homosexual men: the EXPLORE study | journal = Journal of the National Cancer Institute | volume = 97 | issue = 12 | pages = 896–905 | date = June 2005 | pmid = 15956651 | doi = 10.1093/jnci/dji163 | doi-access = free }} No consensus exists, though, that such screening is beneficial, or who should get an anal Pap smear.{{cite web |url=http://www.aidsmeds.com/articles/aids_anal_pap_2042_14727.shtml |title=AIDSmeds Web Exclusives: Pap Smears for Anal Cancer? — by David Evans |publisher=AIDSmeds.com |access-date=29 August 2010 |archive-url=https://web.archive.org/web/20110707094737/http://www.aidsmeds.com/articles/aids_anal_pap_2042_14727.shtml |archive-date=7 July 2011 |date=10 June 2008 |last1=Evans |first1=David }}{{cite journal | vauthors = Goldie SJ, Kuntz KM, Weinstein MC, Freedberg KA, Palefsky JM | title = Cost-effectiveness of screening for anal squamous intraepithelial lesions and anal cancer in human immunodeficiency virus-negative homosexual and bisexual men | journal = The American Journal of Medicine | volume = 108 | issue = 8 | pages = 634–41 | date = June 2000 | pmid = 10856411 | doi = 10.1016/S0002-9343(00)00349-1 }}

HPV is associated with approximately 50% of penile cancers. In the United States, penile cancer accounts for about 0.5% of all cancer cases in men. HPV16 is the most commonly associated type detected. The risk of penile cancer increases 2- to 3-fold for individuals who are infected with HIV as well as HPV.

{{See also|HPV-mediated oropharyngeal cancer}}

Oral infection with high-risk carcinogenic HPV types (most commonly HPV 16) is associated with an increasing number of head and neck cancers.{{Cite periodical |url=https://www.cdc.gov/mmwr/volumes/67/wr/pdfs/mm6733a2-H.pdf|title=Trends in Human Papillomavirus–Associated Cancers—United States, 1999–2015 |periodical=Morbidity and Mortality Weekly Report |volume=67 |issue=33 |author=Elizabeth A. Van Dyne |author2=S. Jane Henley |author3=Mona Saraiya |author4=Cheryll C. Thomas |author5=Lauri E. Markowitz |author6=Vicki B. Benard |date=24 August 2018}}{{cite journal | vauthors = D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML | title = Case-control study of human papillomavirus and oropharyngeal cancer | journal = The New England Journal of Medicine | volume = 356 | issue = 19 | pages = 1944–56 | date = May 2007 | pmid = 17494927 | doi = 10.1056/NEJMoa065497 | s2cid = 18819678 | doi-access = free }}Ridge JA, Glisson BS, Lango MN, et al. [http://www.cancernetwork.com/cancer-management-11/chapter04/article/10165/1402663 "Head and Neck Tumors"] {{webarchive|url=https://web.archive.org/web/20090720201346/http://www.cancernetwork.com/cancer-management-11/chapter04/article/10165/1402663 |date=20 July 2009 }} in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) [http://www.cancernetwork.com/cancer-management-11/ Cancer Management: A Multidisciplinary Approach] {{webarchive|url=https://web.archive.org/web/20131004224102/http://www.cancernetwork.com/cancer-management-11/ |date=4 October 2013 }}. 11 ed. 2008. This association is independent of tobacco and alcohol use.{{cite journal | vauthors = Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D | title = Evidence for a causal association between human papillomavirus and a subset of head and neck cancers | journal = Journal of the National Cancer Institute | volume = 92 | issue = 9 | pages = 709–20 | date = May 2000 | pmid = 10793107 | doi = 10.1093/jnci/92.9.709 | doi-access = free }}{{cite journal | vauthors = Gillison ML | title = Human papillomavirus and prognosis of oropharyngeal squamous cell carcinoma: implications for clinical research in head and neck cancers | journal = Journal of Clinical Oncology | volume = 24 | issue = 36 | pages = 5623–5 | date = December 2006 | pmid = 17179099 | doi = 10.1200/JCO.2006.07.1829 | s2cid = 32491893 | doi-access = free }}

The local percentage varies widely, from 70% in the United States{{cite journal | vauthors = Saraiya M, Unger ER, Thompson TD, Lynch CF, Hernandez BY, Lyu CW, Steinau M, Watson M, Wilkinson EJ, Hopenhayn C, Copeland G, Cozen W, Peters ES, Huang Y, Saber MS, Altekruse S, Goodman MT | title = US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines | journal = Journal of the National Cancer Institute | volume = 107 | issue = 6 | pages = djv086 | date = June 2015 | pmid = 25925419 | pmc = 4838063 | doi = 10.1093/jnci/djv086 }} to 4% in Brazil.{{cite journal | vauthors = Anantharaman D, Abedi-Ardekani B, Beachler DC, Gheit T, Olshan AF, Wisniewski K, Wunsch-Filho V, Toporcov TN, Tajara EH, Levi JE, Moyses RA, Boccia S, Cadoni G, Rindi G, Ahrens W, Merletti F, Conway DI, Wright S, Carreira C, Renard H, Chopard P, McKay-Chopin S, Scelo G, Tommasino M, Brennan P, D'Souza G | title = Geographic heterogeneity in the prevalence of human papillomavirus in head and neck cancer | journal = International Journal of Cancer | volume = 140 | issue = 9 | pages = 1968–1975 | date = May 2017 | pmid = 28108990 | doi = 10.1002/ijc.30608 | pmc = 8969079 | s2cid = 34198821 | hdl = 2318/1634649 | hdl-access = free }} Engaging in anal or oral sex with an HPV-infected partner may increase the risk of developing these types of cancers.

In the United States, the number of newly diagnosed, HPV-associated head and neck cancers has surpassed that of cervical cancer cases. The rate of such cancers has increased from an estimated 0.8 cases per 100,000 people in 1988{{cite journal | vauthors = Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML | title = Human papillomavirus and rising oropharyngeal cancer incidence in the United States | journal = Journal of Clinical Oncology | volume = 29 | issue = 32 | pages = 4294–301 | date = November 2011 | pmid = 21969503 | pmc = 3221528 | doi = 10.1200/JCO.2011.36.4596 }} to 4.5 per 100,000 in 2012, and, as of 2021, the rate has continued to increase.{{Cite journal |last1=Drake |first1=Virginia |last2=Fakhry |first2=Carole |last3=Windon |first3=Melina J. |last4=Stewart |first4=C. Matthew |last5=Akst |first5=Lee |last6=Hillel |first6=Alexander |last7=Chien |first7=Wade |last8=Ha |first8=Patrick |last9=Miles |first9=Brett |last10=Gourin |first10=Christine G. |last11=Mandal |first11=Rajarsi |last12=Mydlarz |first12=Wojciech K. |last13=Rooper |first13=Lisa |last14=Troy |first14=Tanya |last15=Yavvari |first15=Siddhartha |title=Timing, number, and type of sexual partners associated with risk of oropharyngeal cancer |journal=Cancer |language=en |volume=127 |issue=7 |pages=1029–1038 |doi=10.1002/cncr.33346 |date=11 January 2021 |issn=0008-543X |pmc=8035131 |pmid=33426652}} Researchers explain these recent data by an increase in oral sex. This type of cancer is more common in men than in women.{{cite journal | vauthors = Ernster JA, Sciotto CG, O'Brien MM, Finch JL, Robinson LJ, Willson T, Mathews M | title = Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus | journal = The Laryngoscope | volume = 117 | issue = 12 | pages = 2115–28 | date = December 2007 | pmid = 17891052 | doi = 10.1097/MLG.0b013e31813e5fbb | s2cid = 38017888 }}

The mutational profile of HPV-positive and HPV-negative head and neck cancer has been reported, further demonstrating that they are fundamentally distinct diseases.{{cite journal | vauthors = Lechner M, Frampton GM, Fenton T, Feber A, Palmer G, Jay A, Pillay N, Forster M, Cronin MT, Lipson D, Miller VA, Brennan TA, Henderson S, Vaz F, O'Flynn P, Kalavrezos N, Yelensky R, Beck S, Stephens PJ, Boshoff C | title = Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors | journal = Genome Medicine | volume = 5 | issue = 5 | page = 49 | year = 2013 | pmid = 23718828 | pmc = 4064312 | doi = 10.1186/gm453 | doi-access = free }}

Some evidence links HPV to benign and malignant tumors of the upper respiratory tract. The International Agency for Research on Cancer has found that people with lung cancer were significantly more likely to have several high-risk forms of HPV antibodies compared to those who did not have lung cancer.{{cite web|title=Lung Cancer Risk Rises in the Presence of HPV Antibodies|url=http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=2328|archive-url=https://web.archive.org/web/20120427221343/http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=2328|archive-date=27 April 2012}} Researchers looking for HPV among 1,633 lung cancer patients and 2,729 people without the lung disease found that people with lung cancer had more types of HPV than noncancer patients did, and among lung cancer patients, the chances of having eight types of serious HPV were significantly increased.{{cite web|title=Lung Cancer Patients More Likely to Have High-Risk Human Papillomavirus|url=http://www.cdcnpin.org/scripts/display/NewsDisplay.asp?NewsNbr=57349|work=NPIN|archive-url=https://archive.today/20120727083940/http://www.cdcnpin.org/scripts/display/NewsDisplay.asp?NewsNbr=57349|archive-date=27 July 2012}} In addition, expression of HPV structural proteins by immunohistochemistry and in vitro studies suggest HPV presence in bronchial cancer and its precursor lesions.{{cite journal | vauthors = Syrjänen K, Syrjänen S, Kellokoski J, Kärjä J, Mäntyjärvi R | title = Human papillomavirus (HPV) type 6 and 16 DNA sequences in bronchial squamous cell carcinomas demonstrated by in situ DNA hybridization | journal = Lung | volume = 167 | issue = 1 | pages = 33–42 | year = 1989 | pmid = 2537916 | doi = 10.1007/BF02714928 | s2cid = 2094038 }} Another study detected HPV in the exhaled breath condensate (EBC), bronchial brushing and neoplastic lung tissue of cases, and found a presence of an HPV infection in 16.4% of the subjects affected by nonsmall cell lung cancer, but in none of the controls.{{cite journal | vauthors = Carpagnano GE, Koutelou A, Natalicchio MI, Martinelli D, Ruggieri C, Di Taranto A, Antonetti R, Carpagnano F, Foschino-Barbaro MP | title = HPV in exhaled breath condensate of lung cancer patients | journal = British Journal of Cancer | volume = 105 | issue = 8 | pages = 1183–90 | date = October 2011 | pmid = 21952627 | pmc = 3208494 | doi = 10.1038/bjc.2011.354 }} The reported average frequencies of HPV in lung cancers were 17% and 15% in Europe and the Americas, respectively, and the mean number of HPV in Asian lung cancer samples was 35.7%, with considerable heterogeneity between certain countries and regions.{{cite journal | vauthors = Klein F, Amin Kotb WF, Petersen I | title = Incidence of human papilloma virus in lung cancer | journal = Lung Cancer | volume = 65 | issue = 1 | pages = 13–8 | date = July 2009 | pmid = 19019488 | doi = 10.1016/j.lungcan.2008.10.003 }}

In very rare cases, HPV may cause epidermodysplasia verruciformis (EV) in individuals with a weakened immune system. The virus, unchecked by the immune system, causes the overproduction of keratin by skin cells, resulting in lesions resembling warts or cutaneous horns which can ultimately transform into skin cancer, but the development is not well understood.{{cite news | url=https://www.telegraph.co.uk/news/main.jhtml?xml=/news/2007/11/12/wtree112.xml | location=London | work=The Daily Telegraph | first=Matthew | last=Moore | title=Tree man 'who grew roots' may be cured | date=12 November 2007 | archive-url=https://web.archive.org/web/20071113060629/http://www.telegraph.co.uk/news/main.jhtml?xml=%2Fnews%2F2007%2F11%2F12%2Fwtree112.xml | archive-date=13 November 2007 }}{{cite journal | vauthors = Patel T, Morrison LK, Rady P, Tyring S | title = Epidermodysplasia verruciformis and susceptibility to HPV | journal = Disease Markers | volume = 29 | issue = 3–4 | pages = 199–206 | date = 2010 | pmid = 21178278 | pmc = 3835378 | doi = 10.1155/2010/345436 | doi-access = free }} The specific types of HPV that are associated with EV are HPV5, HPV8, and HPV14.

Sexually transmitted HPV is divided into two categories: low-risk and high-risk. Low-risk HPVs cause warts on or around the genitals. Types 6 and 11 cause 90% of all genital warts and recurrent respiratory papillomatosis, which causes benign tumors in the air passages. High-risk HPVs cause cancer and consist of about twelve identified types. Types 16 and 18 are responsible for causing most of the HPV-caused cancers. These high-risk HPVs cause 5% of the cancers in the world. In the United States, high-risk HPVs cause 3% of all cancer cases in women and 2% in men.{{cite web|url=https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-fact-sheet|title=HPV and Cancer|website=National Cancer Institute|access-date=18 April 2017|url-status=live|archive-url=https://web.archive.org/web/20170418163154/https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-fact-sheet|archive-date=18 April 2017|date=15 May 2015}}

Risk factors for persistent genital HPV infections, which increase the risk of developing cancer, include early age of first sexual intercourse, multiple partners, smoking, and immunosuppression. Genital HPV is spread by sustained direct skin-to-skin contact, with vaginal, anal, and oral sex being the most common methods. Occasionally, it can spread from manual sex or from a mother to her baby during pregnancy.{{cite book| last1 = Hoyle | first1 = Alice | last2 = McGeeney | first2 = Ester |title=Great Relationships and Sex Education|publisher=Taylor and Francis|year=2019|access-date=11 July 2023|isbn=978-1-35118-825-8|url=https://books.google.com/books?id=KE7ADwAAQBAJ&pg=PT261}} HPV is difficult to remove via standard hospital disinfection techniques and may be transmitted in a healthcare setting on re-usable gynecological equipment, such as vaginal ultrasound transducers. The period of communicability is still unknown, but probably at least as long as visible HPV lesions persist. HPV may still be transmitted even after lesions are treated and no longer visible or present.{{Cite book|title=Control of Communicable Diseases Manual| vauthors = Heymann MD |publisher=Apha Press|year=2015|isbn=978-0-87553-018-5|edition=20th|location=Washington D.C.|pages=299–300}}

Although genital HPV types can be transmitted from mother to child during birth, the appearance of genital HPV-related diseases in newborns is rare. However, the lack of appearance does not rule out asymptomatic latent infection, as the virus has proven to be capable of hiding for decades. Perinatal transmission of HPV types 6 and 11 can result in the development of juvenile-onset recurrent respiratory papillomatosis (JORRP). JORRP is very rare, with rates of about 2 cases per 100,000 children in the United States. Although JORRP rates are substantially higher if a woman presents with genital warts at the time of giving birth, the risk of JORRP in such cases is still less than 1%.{{citation needed|date=June 2021}}

Genital HPV infections are transmitted primarily by contact with the genitals, anus, or mouth of an infected sexual partner.{{cite journal | vauthors = Burchell AN, Winer RL, de Sanjosé S, Franco EL | title = Chapter 6: Epidemiology and transmission dynamics of genital HPV infection | journal = Vaccine | volume = 24 | issue = Suppl 3 | pages = S3/52–61 | date = August 2006 | pmid = 16950018 | doi = 10.1016/j.vaccine.2006.05.031 }}

Of the 120 known human papillomaviruses, 51 species and three subtypes infect the genital mucosa.{{cite journal | vauthors = Schmitt M, Depuydt C, Benoy I, Bogers J, Antoine J, Arbyn M, Pawlita M | title = Prevalence and viral load of 51 genital human papillomavirus types and three subtypes | journal = International Journal of Cancer | volume = 132 | issue = 10 | pages = 2395–403 | date = May 2013 | pmid = 23034864 | doi = 10.1002/ijc.27891 | s2cid = 1316857 | doi-access = free }} Fifteen are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), three as probable high-risk (26, 53, and 66), and twelve as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89).

Condoms do not completely protect from the virus because the areas around the genitals, including the inner thigh area, are not covered, thus exposing these areas to the infected person's skin.Egendorf, Laura. Sexually Transmitted Diseases (At Issue Series). New York: Greenhaven Press, 2007.

Studies have shown HPV transmission between the hands and genitals of the same person and sexual partners. Hernandez tested the genitals and dominant hand of each person in 25 heterosexual couples every other month for an average of seven months. She found two couples where the man's genitals infected the woman's hand with high-risk HPV, two where her hand infected his genitals, one where her genitals infected his hand, two each where he infected his own hand, and she infected her own hand.{{cite journal | vauthors = Hernandez BY, Wilkens LR, Zhu X, Thompson P, McDuffie K, Shvetsov YB, Kamemoto LE, Killeen J, Ning L, Goodman MT | title = Transmission of human papillomavirus in heterosexual couples | journal = Emerging Infectious Diseases | volume = 14 | issue = 6 | pages = 888–94 | date = June 2008 | pmid = 18507898 | pmc = 2600292 | doi = 10.3201/eid1406.070616 }} Hands were not the main source of transmission in these 25 couples, but they were significant.{{citation needed|date=May 2021}}

Partridge reports men's fingertips became positive for high-risk HPV at more than half the rate (26% per two years) as their genitals (48%).{{cite journal | vauthors = Giuliano AR, Nielson CM, Flores R, Dunne EF, Abrahamsen M, Papenfuss MR, Markowitz LE, Smith D, Harris RB | title = The optimal anatomic sites for sampling heterosexual men for human papillomavirus (HPV) detection: the HPV detection in men study | journal = The Journal of Infectious Diseases | volume = 196 | issue = 8 | pages = 1146–52 | date = October 2007 | pmid = 17955432 | pmc = 3904649 | doi = 10.1086/521629 }} Winer reports 14% of fingertip samples from sexually active women were positive.{{cite journal | vauthors = Winer RL, Hughes JP, Feng Q, Xi LF, Cherne S, O'Reilly S, Kiviat NB, Koutsky LA | title = Detection of genital HPV types in fingertip samples from newly sexually active female university students | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 19 | issue = 7 | pages = 1682–5 | date = July 2010 | pmid = 20570905 | pmc = 2901391 | doi = 10.1158/1055-9965.EPI-10-0226 }}

Non-sexual hand contact seems to have little or no role in HPV transmission. Winer found all fourteen fingertip samples from virgin women negative at the start of her fingertip study. In a separate report on genital HPV infection, 1% of virgin women (1 of 76) with no sexual contact tested positive for HPV, while 10% of virgin women reporting non-penetrative sexual contact were positive (7 of 72).{{cite journal | vauthors = Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA | title = Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students | journal = American Journal of Epidemiology | volume = 157 | issue = 3 | pages = 218–26 | date = February 2003 | pmid = 12543621 | doi = 10.1093/aje/kwf180 | doi-access = free }}

Sharing of possibly contaminated objects, for example, razors, may transmit HPV.{{cite journal | vauthors = Tay SK | title = Genital oncogenic human papillomavirus infection: a short review on the mode of transmission | journal = Annals of the Academy of Medicine, Singapore | volume = 24 | issue = 4 | pages = 598–601 | date = July 1995 | pmid = 8849195 | url = https://www.nlm.nih.gov/medlineplus/reproductivehealth.html | url-status = live | format = Free full text | archive-url = https://web.archive.org/web/20120727124342/http://www.nlm.nih.gov/medlineplus/reproductivehealth.html | archive-date = 27 July 2012 }}{{cite journal | vauthors = Pao CC, Tsai PL, Chang YL, Hsieh TT, Jin JY | title = Possible non-sexual transmission of genital human papillomavirus infections in young women | journal = European Journal of Clinical Microbiology & Infectious Diseases | volume = 12 | issue = 3 | pages = 221–2 | date = March 1993 | pmid = 8389707 | doi = 10.1007/BF01967118 | s2cid = 11548979 }}{{cite journal | vauthors = Tay SK, Ho TH, Lim-Tan SK | title = Is genital human papillomavirus infection always sexually transmitted? | journal = The Australian & New Zealand Journal of Obstetrics & Gynaecology | volume = 30 | issue = 3 | pages = 240–2 | date = August 1990 | pmid = 2256864 | doi = 10.1111/j.1479-828X.1990.tb03223.x | s2cid = 72353975 | url = https://www.nlm.nih.gov/medlineplus/genitalwarts.html | url-status = live | format = Free full text | archive-url = https://web.archive.org/web/20160406191006/https://www.nlm.nih.gov/medlineplus/genitalwarts.html | archive-date = 6 April 2016 }} Although possible, transmission by routes other than sexual intercourse is less common for female genital HPV infection. Fingers-genital contact is a possible way of transmission, but unlikely to be a significant source.{{cite journal | vauthors = Sonnex C, Strauss S, Gray JJ | title = Detection of human papillomavirus DNA on the fingers of patients with genital warts | journal = Sexually Transmitted Infections | volume = 75 | issue = 5 | pages = 317–9 | date = October 1999 | pmid = 10616355 | pmc = 1758241 | doi = 10.1136/sti.75.5.317 }}

Though it has traditionally been assumed that HPV is not transmissible via blood, as it is thought to only infect cutaneous and mucosal tissues, recent studies have called this notion into question. Historically, HPV DNA has been detected in the blood of cervical cancer patients.{{cite book | author1 = Hans Krueger | author2 = Gavin Stuart | author3 = Richard Gallagher | author4 = Dan Williams, Jon Kerner | title = HPV and Other Infectious Agents in Cancer:Opportunities for Prevention and Public Health: Opportunities for Prevention and Public Health | url = https://books.google.com/books?id=engBMqjQ6SQC&pg=PA34 | access-date = 24 December 2012 | date = 12 April 2010 | publisher = Oxford University Press | isbn = 978-0-19-973291-3 | page = 34 | url-status = live | archive-url = https://web.archive.org/web/20130609085053/http://books.google.com/books?id=engBMqjQ6SQC&pg=PA34 | archive-date = 9 June 2013 }} In 2005, a group reported that, in frozen blood samples of 57 sexually naive pediatric patients who had vertical or transfusion-acquired HIV infection, 8 (14.0%) of these samples also tested positive for HPV-16.{{cite journal | vauthors = Bodaghi S, Wood LV, Roby G, Ryder C, Steinberg SM, Zheng ZM | title = Could human papillomaviruses be spread through blood? | journal = Journal of Clinical Microbiology | volume = 43 | issue = 11 | pages = 5428–34 | date = November 2005 | pmid = 16272465 | pmc = 1287818 | doi = 10.1128/JCM.43.11.5428-5434.2005 }} This seems to indicate that it may be possible for HPV to be transmitted via blood transfusion. However, as non-sexual transmission of HPV by other means is not uncommon, this could not be definitively proven. In 2009, a group tested Australian Red Cross blood samples from 180 healthy male donors for HPV, and subsequently found DNA of one or more strains of the virus in 15 (8.3%) of the samples.{{cite journal | vauthors = Chen AC, Keleher A, Kedda MA, Spurdle AB, McMillan NA, Antonsson A | title = Human papillomavirus DNA detected in peripheral blood samples from healthy Australian male blood donors | journal = Journal of Medical Virology | volume = 81 | issue = 10 | pages = 1792–6 | date = October 2009 | pmid = 19697401 | doi = 10.1002/jmv.21592 | url = https://espace.library.uq.edu.au/view/UQ:202101/MIC15UQ202101.pdf | hdl = 10072/44445 | s2cid = 22918855 | hdl-access = free }} However, it is important to note that detecting the presence of HPV DNA in blood is not the same as detecting the virus itself in blood, and whether or not the virus itself can or does reside in blood in infected individuals is still unknown. As such, it remains to be determined whether HPV can or cannot be transmitted via blood. This is of concern, as blood donations are not currently screened for HPV, and at least some organizations, such as the American Red Cross and other Red Cross societies, do not presently appear to disallow HPV-positive individuals from donating blood.{{cite web | title = Eligibility Criteria by Topic - American Red Cross | url = http://www.redcrossblood.org/donating-blood/eligibility-requirements/eligibility-criteria-topic | url-status = live | archive-url = https://web.archive.org/web/20170101001303/http://www.redcrossblood.org/donating-blood/eligibility-requirements/eligibility-criteria-topic | archive-date = 1 January 2017 }}

Hospital transmission of HPV, especially to surgical staff, has been documented. Surgeons, including urologists and/or anyone in the room, are subject to HPV infection by inhalation of noxious viral particles during electrocautery or laser ablation of a condyloma (wart).{{cite journal | vauthors = Watson RA | title = Human Papillomavirus: Confronting the Epidemic-A Urologist's Perspective | journal = Reviews in Urology | volume = 7 | issue = 3 | pages = 135–44 | year = 2005 | pmid = 16985824 | pmc = 1477576 }} There has been a case report of a laser surgeon who developed extensive laryngeal papillomatosis after providing laser ablation to patients with anogenital condylomata.

File:5keq.png structure of the HPV type 16 viral capsid protein. Rendered from {{PDB|5KEQ}}{{cite journal | vauthors = Guan J, Bywaters SM, Brendle SA, Ashley RE, Makhov AM, Conway JF, Christensen ND, Hafenstein S | title = Cryoelectron Microscopy Maps of Human Papillomavirus 16 Reveal L2 Densities and Heparin Binding Site | journal = Structure | volume = 25 | issue = 2 | pages = 253–263 | date = February 2017 | pmid = 28065506 | doi = 10.1016/j.str.2016.12.001 | doi-access = free }}]]

HPV infection is limited to the basal cells of stratified epithelium, the only tissue in which they replicate.{{cite journal | vauthors = Schiller JT, Day PM, Kines RC | title = Current understanding of the mechanism of HPV infection | journal = Gynecologic Oncology | volume = 118 | issue = 1 Suppl | pages = S12–7 | date = June 2010 | pmid = 20494219 | pmc = 3493113 | doi = 10.1016/j.ygyno.2010.04.004 }} The virus cannot bind to live tissue; instead, it infects epithelial tissues through micro-abrasions or other epithelial trauma that exposes segments of the basement membrane. The infectious process is slow, taking 12–24 hours for initiation of transcription. It is believed that the involved antibodies play a major neutralizing role while the virions still reside on the basement membrane and cell surfaces.

HPV lesions are thought to arise from the proliferation of infected basal keratinocytes. Infection typically occurs when basal cells in the host are exposed to the infectious virus through a disturbed epithelial barrier, as would occur during sexual intercourse or after minor skin abrasions. HPV infections are not cytolytic; rather, viral particles are released as a result of the degeneration of desquamating cells. HPV can survive for many months and at low temperatures without a host; therefore, an individual with plantar warts can spread the virus by walking barefoot.{{cite journal|url=http://emedicine.medscape.com/article/219110-overview#a3|title=Human Papillomavirus|website=Medscape|url-status=live|archive-url=https://web.archive.org/web/20161129152008/http://emedicine.medscape.com/article/219110-overview#a3|archive-date=29 November 2016|date=16 October 2018}}

HPV is a small double-stranded circular DNA virus with a genome of approximately 8000 base pairs.{{cite journal | vauthors = Pahud BA, Ault KA | title = The Expanded Impact of Human Papillomavirus Vaccine | journal = Infectious Disease Clinics of North America | volume = 29 | issue = 4 | pages = 715–24 | date = December 2015 | pmid = 26610422 | doi = 10.1016/j.idc.2015.07.007 | type = Review }}{{cite journal | vauthors = Scheurer ME, Tortolero-Luna G, Adler-Storthz K | title = Human papillomavirus infection: biology, epidemiology, and prevention | journal = International Journal of Gynecological Cancer | volume = 15 | issue = 5 | pages = 727–46 | year = 2005 | pmid = 16174218 | doi = 10.1111/j.1525-1438.2005.00246.x | s2cid = 23849159 }} The HPV life cycle strictly follows the differentiation program of the host keratinocyte. It is thought that the HPV virion infects epithelial tissues through micro-abrasions, whereby the virion associates with putative receptors such as alpha integrins, laminins, and annexin A2{{cite journal | vauthors = Woodham AW, Da Silva DM, Skeate JG, Raff AB, Ambroso MR, Brand HE, Isas JM, Langen R, Kast WM | title = The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection | journal = PLOS ONE | volume = 7 | issue = 8 | pages = e43519 | date = 2012 | pmid = 22927980 | pmc = 3425544 | doi = 10.1371/journal.pone.0043519 | bibcode = 2012PLoSO...743519W | doi-access = free }} leading to the entry of the virions into basal epithelial cells through clathrin-mediated endocytosis and/or caveolin-mediated endocytosis depending on the type of HPV.{{cite journal | vauthors = Raff AB, Woodham AW, Raff LM, Skeate JG, Yan L, Da Silva DM, Schelhaas M, Kast WM | title = The evolving field of human papillomavirus receptor research: a review of binding and entry | journal = Journal of Virology | volume = 87 | issue = 11 | pages = 6062–72 | date = June 2013 | pmid = 23536685 | pmc = 3648114 | doi = 10.1128/JVI.00330-13 }} At this point, the viral genome is transported to the nucleus by unknown mechanisms and establishes itself at a copy number of 10-200 viral genomes per cell. A sophisticated transcriptional cascade then occurs as the host keratinocyte begins to divide and become increasingly differentiated in the upper layers of the epithelium.{{citation needed|date=May 2021}}

The phylogeny of the various strains of HPV generally reflects the migration patterns of Homo sapiens and suggests that HPV may have diversified along with the human population. Studies suggest that HPV evolved along five major branches that reflect the ethnicity of human hosts, and diversified along with the human population.{{cite journal | vauthors = Chen Z, Schiffman M, Herrero R, Desalle R, Anastos K, Segondy M, Sahasrabuddhe VV, Gravitt PE, Hsing AW, Burk RD | title = Evolution and taxonomic classification of human papillomavirus 16 (HPV16)-related variant genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67 | journal = PLOS ONE | volume = 6 | issue = 5 | pages = e20183 | year = 2011 | pmid = 21673791 | pmc = 3103539 | doi = 10.1371/journal.pone.0020183 | bibcode = 2011PLoSO...620183C | doi-access = free }}

Researchers initially identified two major variants of HPV16, European (HPV16-E), and Non-European (HPV16-NE).{{cite journal | vauthors = Zuna RE, Tuller E, Wentzensen N, Mathews C, Allen RA, Shanesmith R, Dunn ST, Gold MA, Wang SS, Walker J, Schiffman M | title = HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer | journal = Infectious Agents and Cancer | volume = 6 | page = 19 | date = October 2011 | pmid = 22035468 | pmc = 3226431 | doi = 10.1186/1750-9378-6-19 | doi-access = free }} More recent analyses based on thousands of HPV16 genomes show that indeed two major clades exist, that are further subdivided into four lineages (designated A-D) and even further subdivided into 16 sublineages (A1–4, B1–4, C1–4 and D1–4).{{Cite journal|last1=Mirabello|first1=Lisa|last2=Clarke|first2=Megan|last3=Nelson|first3=Chase|last4=Dean|first4=Michael|last5=Wentzensen|first5=Nicolas|last6=Yeager|first6=Meredith|last7=Cullen|first7=Michael|last8=Boland|first8=Joseph|last9=NCI HPV Workshop|last10=Schiffman|first10=Mark|last11=Burk|first11=Robert|date=13 February 2018|title=The Intersection of HPV Epidemiology, Genomics and Mechanistic Studies of HPV-Mediated Carcinogenesis|journal=Viruses|language=en|volume=10|issue=2|page=80|doi=10.3390/v10020080|issn=1999-4915|pmc=5850387|pmid=29438321|doi-access=free}}{{Cite journal|last1=Nikolaidis|first1=Marios|last2=Tsakogiannis|first2=Dimitris|last3=Bletsa|first3=Garyfalia|last4=Mossialos|first4=Dimitris|last5=Kottaridi|first5=Christine|last6=Iliopoulos|first6=Ioannis|last7=Markoulatos|first7=Panayotis|last8=Amoutzias|first8=Grigoris D.|date=14 October 2021|title=HPV16-Genotyper: A Computational Tool for Risk-Assessment, Lineage Genotyping and Recombination Detection in HPV16 Sequences, Based on a Large-Scale Evolutionary Analysis|journal=Diversity|language=en|volume=13|issue=10|page=497|doi=10.3390/d13100497|issn=1424-2818|doi-access=free|bibcode=2021Diver..13..497N }} The A1-A3 sublineages constitute the European variant, A4 the Asian variant, B1-B4 the African type I variant, C1–C4 the African type II variant, D1 the North American variant, D2 the Asian American type I variant, D3 the Asian American type II variant. The various lineages and sublineages have different oncogenic capacity, where overall, the non-European lineages are considered to increase the risk for cancer.{{Cite journal|last1=Mirabello|first1=Lisa|last2=Yeager|first2=Meredith|last3=Cullen|first3=Michael|last4=Boland|first4=Joseph F.|last5=Chen|first5=Zigui|last6=Wentzensen|first6=Nicolas|last7=Zhang|first7=Xijun|last8=Yu|first8=Kai|last9=Yang|first9=Qi|last10=Mitchell|first10=Jason|last11=Roberson|first11=David|date=September 2016|title=HPV16 Sublineage Associations With Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women|journal=Journal of the National Cancer Institute|language=en|volume=108|issue=9|pages=djw100|doi=10.1093/jnci/djw100|issn=0027-8874|pmc=5939630|pmid=27130930}} Although HPV16 is a DNA virus, there are signs of recombination among the different lineages.{{Cite journal|last1=Jiang|first1=Mingjun|last2=Xi|first2=Long Fu|last3=Edelstein|first3=Zoe R.|last4=Galloway|first4=Denise A.|last5=Olsem|first5=Gary J.|last6=Lin|first6=William Chun-Che|last7=Kiviat|first7=Nancy B.|date=November 2009|title=Identification of recombinant human papillomavirus type 16 variants|journal=Virology|language=en|volume=394|issue=1|pages=8–11|doi=10.1016/j.virol.2009.08.040|pmc=2769496|pmid=19758676}} Based on an analysis of more than 3600 genomes, between 0.3 and 1.2% of them could be recombinant. Thus, ideally, genotyping (for cancer-risk assessment) of HPV16 should not be based only on certain genes, but on all genes from the entire genome.

A bioinformatics tool named HPV16-Genotyper performs i) HPV16 lineage genotyping, ii) detects potential recombination events, iii) identifies, within the submitted sequences, mutations/SNPs that have been reported (in literature) to increase the risk for cancer.

File:4giz.E6.png, shown bound to the LxxLL peptide motif of the human protein UBE3A (cyan). Rendered from {{PDB|4GIZ}}.{{cite journal | vauthors = Zanier K, Charbonnier S, Sidi AO, McEwen AG, Ferrario MG, Poussin-Courmontagne P, Cura V, Brimer N, Babah KO, Ansari T, Muller I, Stote RH, Cavarelli J, Vande Pol S, Travé G | title = Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins | journal = Science | volume = 339 | issue = 6120 | pages = 694–8 | date = February 2013 | pmid = 23393263 | pmc = 3899395 | doi = 10.1126/science.1229934 | bibcode = 2013Sci...339..694Z }}]]

The two primary oncoproteins of high-risk HPV types are E6 and E7. The "E" designation indicates that these two proteins are early proteins (expressed early in the HPV life cycle), while the "L" designation indicates that they are late proteins (late expression). The HPV genome is composed of six early (E1, E2, E4, E5, E6, and E7) open reading frames (ORF), two late (L1 and L2) ORFs, and a non-coding long control region (LCR).{{cite journal | vauthors = Ganguly N, Parihar SP | title = Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis | journal = Journal of Biosciences | volume = 34 | issue = 1 | pages = 113–23 | date = March 2009 | pmid = 19430123 | doi = 10.1007/s12038-009-0013-7 | s2cid = 8770549 }} After the host cell is infected viral early promoter is activated and a polycistronic primary RNA containing all six early ORFs is transcribed. This polycistronic RNA then undergoes active RNA splicing to generate multiple isoforms of mRNAs.{{cite journal | vauthors = Zheng ZM, Baker CC | title = Papillomavirus genome structure, expression, and post-transcriptional regulation | journal = Frontiers in Bioscience | volume = 11 | pages = 2286–302 | date = September 2006 | pmid = 16720315 | pmc = 1472295 | doi = 10.2741/1971 }} One of the spliced isoform RNAs, E6*I, serves as an E7 mRNA to translate E7 protein.{{cite journal | vauthors = Tang S, Tao M, McCoy JP, Zheng ZM | title = The E7 oncoprotein is translated from spliced E6*I transcripts in high-risk human papillomavirus type 16- or type 18-positive cervical cancer cell lines via translation reinitiation | journal = Journal of Virology | volume = 80 | issue = 9 | pages = 4249–63 | date = May 2006 | pmid = 16611884 | pmc = 1472016 | doi = 10.1128/JVI.80.9.4249-4263.2006 }} However, viral early transcription subjects to viral E2 regulation and high E2 levels repress the transcription. HPV genomes integrate into the host genome by disruption of the E2 ORF, preventing E2 repression of E6 and E7. Thus, viral genome integration into the host DNA genome increases E6 and E7 expression to promote cellular proliferation and the chance of malignancy. The degree to which E6 and E7 are expressed is correlated with the type of cervical lesion that can ultimately develop.

;Role in cancer

Sometimes papillomavirus genomes are found integrated into the host genome, and this is especially noticeable with oncogenic HPVs.{{cite Q |1=Q39186071}} The E6/E7 proteins inactivate two tumor suppressor proteins, p53 (inactivated by E6) and pRb (inactivated by E7).{{cite book|last1=Chaturvedi|first1=Anil|first2 = Maura L. | last2 = Gillison |title=Epidemiology, Pathogenesis, and Prevention of Head and Neck Cancer|editor=Andrew F. Olshan |publisher=Springer|location=New York|date=4 March 2010|pages=87–116 |edition=1st |chapter=Human Papillomavirus and Head and Neck Cancer |isbn=978-1-4419-1471-2|doi=10.1007/978-1-4419-1472-9_5}} The viral oncogenes E6 and E7{{cite journal | vauthors = Münger K, Howley PM | title = Human papillomavirus immortalization and transformation functions | journal = Virus Research | volume = 89 | issue = 2 | pages = 213–28 | date = November 2002 | pmid = 12445661 | doi = 10.1016/S0168-1702(02)00190-9 }} are thought to modify the cell cycle so as to retain the differentiating host keratinocyte in a state that is favourable to the amplification of viral genome replication and consequent late gene expression. E6 in association with host E6-associated protein, which has ubiquitin ligase activity, acts to ubiquitinate p53, leading to its proteosomal degradation. E7 (in oncogenic HPVs) acts as the primary transforming protein. E7 competes for retinoblastoma protein (pRb) binding, freeing the transcription factor E2F to transactivate its targets, thus pushing the cell cycle forward. All HPV strains can induce transient proliferation, but only strains 16 and 18 can immortalize cell lines in vitro. It has also been shown that HPV 16 and 18 cannot immortalize primary rat cells alone; there needs to be activation of the ras oncogene. In the upper layers of the host epithelium, the late genes L1 and L2 are transcribed/translated and serve as structural proteins that encapsidate the amplified viral genomes. Once the genome is encapsidated, the capsid appears to undergo a redox-dependent assembly/maturation event, which is tied to a natural redox gradient that spans both suprabasal and cornified epithelial tissue layers. This assembly/maturation event stabilizes virions and increases their specific infectivity.

{{cite journal | vauthors = Conway MJ, Alam S, Ryndock EJ, Cruz L, Christensen ND, Roden RB, Meyers C | title = Tissue-spanning redox gradient-dependent assembly of native human papillomavirus type 16 virions | journal = Journal of Virology | volume = 83 | issue = 20 | pages = 10515–26 | date = October 2009 | pmid = 19656879 | pmc = 2753102 | doi = 10.1128/JVI.00731-09 }} Virions can then be sloughed off in the dead squames of the host epithelium and the viral lifecycle continues.

{{cite journal | vauthors = Bryan JT, Brown DR | title = Transmission of human papillomavirus type 11 infection by desquamated cornified cells | journal = Virology | volume = 281 | issue = 1 | pages = 35–42 | date = March 2001 | pmid = 11222093 | doi = 10.1006/viro.2000.0777 | doi-access = free }} A 2010 study has found that E6 and E7 are involved in beta-catenin nuclear accumulation and activation of Wnt signaling in HPV-induced cancers.{{cite journal | vauthors = Rampias T, Boutati E, Pectasides E, Sasaki C, Kountourakis P, Weinberger P, Psyrri A | title = Activation of Wnt signaling pathway by human papillomavirus E6 and E7 oncogenes in HPV16-positive oropharyngeal squamous carcinoma cells | journal = Molecular Cancer Research | volume = 8 | issue = 3 | pages = 433–43 | date = March 2010 | pmid = 20215420 | doi = 10.1158/1541-7786.MCR-09-0345 | s2cid = 19411033 | doi-access = free }}

Once an HPV virion invades a cell, an active infection occurs, and the virus can be transmitted. Several months to years may elapse before squamous intraepithelial lesions (SIL) develop and can be clinically detected. The time from active infection to clinically detectable disease may make it difficult for epidemiologists to establish which partner was the source of infection.

Most HPV infections are cleared up by most people without medical action or consequences. The table provides data for high-risk types (i.e., the types found in cancers).{{citation needed|date=May 2021}}

Clearing an infection does not always create immunity if there is a new or continuing source of infection. Hernandez' 2005-6 study of 25 couples reports "A number of instances indicated apparent reinfection [from partner] after viral clearance."

Image:HPV tree 1.png

Over 200 types of HPV have been identified, and they are designated by numbers.{{cite journal | vauthors = Bzhalava D, Guan P, Franceschi S, Dillner J, Clifford G | title = A systematic review of the prevalence of mucosal and cutaneous human papillomavirus types | journal = Virology | volume = 445 | issue = 1–2 | pages = 224–31 | date = October 2013 | pmid = 23928291 | doi = 10.1016/j.virol.2013.07.015 | doi-access = free }} They may be divided into "low-risk" and "high-risk" types. Low-risk types cause warts and high-risk types can cause lesions or cancer.{{cite journal | vauthors = Schiffman M, Castle PE | title = Human papillomavirus: epidemiology and public health | journal = Archives of Pathology & Laboratory Medicine | volume = 127 | issue = 8 | pages = 930–4 | date = August 2003 | pmid = 12873163 | doi = 10.5858/2003-127-930-HPEAPH | url = http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2003)127%3C930:HPEAPH%3E2.0.CO;2 | trans-title = 1 January 2017 | archive-url = https://archive.today/20130414113933/http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2003)127%3C930:HPEAPH%3E2.0.CO;2 | archive-date = 14 April 2013 | url-access = subscription }}{{Cite news|url=https://medlineplus.gov/hpv.html|title=HPV {{!}} Human Papillomavirus {{!}} Pap Smear {{!}} MedlinePlus|access-date=7 November 2018}}

{{Main|Cervical screening}}

Guidelines from the American Cancer Society recommend different screening strategies for cervical cancer based on a woman's age, screening history, risk factors, and choice of tests.{{cite journal |last1=Saslow |first1=D |last2=Solomon |first2=D |last3=Lawson |first3=HW |last4=Killackey |first4=M |last5=Kulasingam |first5=SL |last6=Cain |first6=J |last7=Garcia |first7=FA |last8=Moriarty |first8=AT |last9=Waxman |first9=AG |last10=Wilbur |first10=DC |last11=Wentzensen |first11=N |last12=Downs LS |first12=Jr |last13=Spitzer |first13=M |last14=Moscicki |first14=AB |last15=Franco |first15=EL |last16=Stoler |first16=MH |last17=Schiffman |first17=M |last18=Castle |first18=PE |last19=Myers |first19=ER |author20=ACS-ASCCP-ASCP Cervical Cancer Guideline Committee |title=American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. |journal=CA: A Cancer Journal for Clinicians |date=May 2012 |volume=62 |issue=3 |pages=147–72 |doi=10.3322/caac.21139 |pmid=22422631 |pmc=3801360}} Because of the link between HPV and cervical cancer, the ACS currently recommends early detection of cervical cancer in average-risk asymptomatic adults primarily with cervical cytology by Pap smear, regardless of HPV vaccination status. Women aged 30–65 should preferably be tested every 5 years with both the HPV test and the Pap test. In other age groups, a Pap test alone can suffice unless they have been diagnosed with atypical squamous cells of undetermined significance (ASC-US).{{cite journal | vauthors = Smith RA, Andrews KS, Brooks D, Fedewa SA, Manassaram-Baptiste D, Saslow D, Brawley OW, Wender RC | title = Cancer screening in the United States, 2017: A review of current American Cancer Society guidelines and current issues in cancer screening | journal = CA: A Cancer Journal for Clinicians | volume = 67 | issue = 2 | pages = 100–121 | date = March 2017 | pmid = 28170086 | doi = 10.3322/caac.21392 | s2cid = 37359995 | doi-access = free }} Co-testing with a Pap test and HPV test is recommended because it decreases the rate of false-negatives. According to the National Cancer Institute, "The most common test detects DNA from several high-risk HPV types, but it cannot identify the types that are present. Another test is specific for DNA from HPV types 16 and 18, the two types that cause most HPV-associated cancers. A third test can detect DNA from several high-risk HPV types and can indicate whether HPV-16 or HPV-18 is present. A fourth test detects RNA from the most common high-risk HPV types. These tests can detect HPV infections before cell abnormalities are evident.{{citation needed|date=May 2021}}

"Theoretically, the HPV DNA and RNA tests could be used to identify HPV infections in cells taken from any part of the body. However, the tests are approved by the FDA for only two indications: for follow-up testing of women who seem to have abnormal Pap test results and for cervical cancer screening in combination with a Pap test among women over age 30."{{cite web|title=National Cancer Institute Fact Sheet: HPV and Cancer|url=http://www.cancer.gov/cancertopics/factsheet/Risk/HPV|publisher=Cancer.gov|access-date=23 October 2013|url-status=live|archive-url=https://web.archive.org/web/20131031233555/http://www.cancer.gov/cancertopics/factsheet/Risk/HPV|archive-date=31 October 2013}}

Guidelines for oropharyngeal cancer screening by the Preventive Services Task Force and American Dental Association in the U.S. suggest conventional visual examination, but because some parts of the oropharynx are hard to see, this cancer is often only detected in later stages.

The diagnosis of oropharyngeal cancer occurs by biopsy of exfoliated cells or tissues. The National Comprehensive Cancer Network and College of American Pathologists recommend testing for HPV in oropharyngeal cancer. However, while testing is recommended, there is no specific type of test used to detect HPV from oral tumors that is currently recommended by the FDA in the United States. Because HPV type 16 is the most common type found in oropharyngeal cancer, p16 immunohistochemistry is one test option used to determine if HPV is present,{{cite journal | vauthors = Pan C, Issaeva N, Yarbrough WG | title = HPV-driven oropharyngeal cancer: current knowledge of molecular biology and mechanisms of carcinogenesis | journal = Cancers of the Head & Neck | volume = 3 | page = 12 | date = 2018 | pmid = 31093365 | pmc = 6460765 | doi = 10.1186/s41199-018-0039-3 | doi-access = free }} which can help determine course of treatment since tumors that are negative for p16 have better outcomes. Another option that has emerged as a reliable option is HPV DNA in situ hybridization (ISH), which allows for visualization of the HPV.

There is not a wide range of tests available, even though HPV is common; most studies of HPV used tools and custom analysis not available to the general public.{{update after|2015|5|4}} Clinicians often depend on the vaccine among young people and high clearance rates (see Clearance subsection in Virology) to create a low risk of disease and mortality, and treat the cancers when they appear. Others believe that reducing HPV infection in more men and women, even when it has no symptoms, is important (herd immunity) to prevent more cancers rather than just treating them.{{cite journal | vauthors = Burchell AN, Richardson H, Mahmud SM, Trottier H, Tellier PP, Hanley J, Coutlée F, Franco EL | title = Modeling the sexual transmissibility of human papillomavirus infection using stochastic computer simulation and empirical data from a cohort study of young women in Montreal, Canada | journal = American Journal of Epidemiology | volume = 163 | issue = 6 | pages = 534–43 | date = March 2006 | pmid = 16421235 | doi = 10.1093/aje/kwj077 | doi-access = free }}{{cite journal | vauthors = Kim JJ | title = Vaccine policy analyses can benefit from natural history studies of human papillomavirus in men | journal = The Journal of Infectious Diseases | volume = 196 | issue = 8 | pages = 1117–9 | date = October 2007 | pmid = 17955427 | doi = 10.1086/521199 | doi-access = free }}{{update after|2015|5|4}} Where tests are used, negative test results show safety from transmission, and positive test results show where shielding (condoms, gloves) is needed to prevent transmission until the infection clears.{{cite web|url=http://www.thehpvtest.com/about-hpv/faqs-for-men/#Should-you-stop-having-sex-with-your-partner-if-she-finds-out|title=FAQs for Men|work=thehpvtest.com|archive-url=https://web.archive.org/web/20120905173128/http://www.thehpvtest.com/about-hpv/faqs-for-men#Should-you-stop-having-sex-with-your-partner-if-she-finds-out|archive-date=5 September 2012|access-date=24 August 2012}}

Studies have tested for and found HPV in men, including high-risk types (i.e. the types found in cancers), on fingers, mouth, saliva, anus, urethra, urine, semen, blood, scrotum and penis.{{cite journal | vauthors = Dunne EF, Nielson CM, Stone KM, Markowitz LE, Giuliano AR | title = Prevalence of HPV infection among men: A systematic review of the literature | journal = The Journal of Infectious Diseases | volume = 194 | issue = 8 | pages = 1044–57 | date = October 2006 | pmid = 16991079 | doi = 10.1086/507432 | doi-access = free }}

The aforementioned Qiagen/Digene kit was successfully used off-label to test the penis, scrotum, and anus of men in long-term relationships with women who were positive for high-risk HPV. Of these men, 60% were found to carry the virus, primarily on the penis.{{cite journal | vauthors = Nicolau SM, Camargo CG, Stávale JN, Castelo A, Dôres GB, Lörincz A, de Lima GR | title = Human papillomavirus DNA detection in male sexual partners of women with genital human papillomavirus infection | journal = Urology | volume = 65 | issue = 2 | pages = 251–5 | date = February 2005 | pmid = 15708032 | doi = 10.1016/j.urology.2004.09.031 }}{{update after|2015|5|4}} Similar studies have been conducted on women using cytobrushes - an endocervical brush for sampling the cervix in females - and custom analysis.{{cite journal | vauthors = Aguilar LV, Lazcano-Ponce E, Vaccarella S, Cruz A, Hernández P, Smith JS, Muñoz N, Kornegay JR, Hernández-Avila M, Franceschi S | title = Human papillomavirus in men: comparison of different genital sites | journal = Sexually Transmitted Infections | volume = 82 | issue = 1 | pages = 31–3 | date = February 2006 | pmid = 16461598 | pmc = 2563819 | doi = 10.1136/sti.2005.015131 }}{{update after|2015|5|4}}

In one study researchers sampled subjects' urethra, scrotum, and penis.{{cite journal | vauthors = Weaver BA, Feng Q, Holmes KK, Kiviat N, Lee SK, Meyer C, Stern M, Koutsky LA | title = Evaluation of genital sites and sampling techniques for detection of human papillomavirus DNA in men | journal = The Journal of Infectious Diseases | volume = 189 | issue = 4 | pages = 677–85 | date = February 2004 | pmid = 14767822 | doi = 10.1086/381395 | doi-access = free }}{{update after|2015|5|4}} Samples taken from the urethra added less than 1% to the HPV rate. Studies like this led Giuliano to recommend sampling the glans, shaft, and crease between them, along with the scrotum, since sampling the urethra or anus added very little to the diagnosis. Dunne recommends the glans, shaft, their crease, and the foreskin.

In one study the subjects were asked not to wash their genitals for 12 hours before sampling, including the urethra as well as the scrotum and the penis. Other studies are silent on washing – a particular gap in studies of the hands.{{citation needed|date=June 2021}}

One small study used wet cytobrushes, rather than wetting the skin. It found a higher proportion of men to be HPV-positive when the skin was rubbed with a 600 grit emery paper before being swabbed with the brush, rather than swabbed with no preparation. It's unclear whether the emery paper collected the virions or simply loosened them for the swab to collect.{{citation needed|date=November 2022}}

Studies have found self-collection (with emery paper and Dacron swabs) as effective as collection done by a clinician, and sometimes more so, since patients were more willing than a clinician to scrape vigorously.{{cite journal | vauthors = Hernandez BY, McDuffie K, Goodman MT, Wilkens LR, Thompson P, Zhu X, Wong W, Ning L | title = Comparison of physician- and self-collected genital specimens for detection of human papillomavirus in men | journal = Journal of Clinical Microbiology | volume = 44 | issue = 2 | pages = 513–7 | date = February 2006 | pmid = 16455906 | pmc = 1392697 | doi = 10.1128/JCM.44.2.513-517.2006 }}{{update after|2015|5|4}}{{cite journal | vauthors = Ogilvie GS, Taylor DL, Achen M, Cook D, Krajden M | title = Self-collection of genital human papillomavirus specimens in heterosexual men | journal = Sexually Transmitted Infections | volume = 85 | issue = 3 | pages = 221–5 | date = June 2009 | pmid = 19066196 | doi = 10.1136/sti.2008.033068 | s2cid = 24410167 | doi-access = free }} Women had similar success in self-sampling using tampons, swabs, cytobrushes, and lavage.{{cite journal | vauthors = Petignat P, Faltin DL, Bruchim I, Tramèr MR, Franco EL, Coutlée F | title = Are self-collected samples comparable to physician-collected cervical specimens for human papillomavirus DNA testing? A systematic review and meta-analysis | journal = Gynecologic Oncology | volume = 105 | issue = 2 | pages = 530–5 | date = May 2007 | pmid = 17335880 | doi = 10.1016/j.ygyno.2007.01.023 }}{{update after|2015|5|4}}

Several studies used cytobrushes to sample fingertips and under fingernails, without wetting the area or the brush.{{cite journal | vauthors = Partridge JM, Hughes JP, Feng Q, Winer RL, Weaver BA, Xi LF, Stern ME, Lee SK, O'Reilly SF, Hawes SE, Kiviat NB, Koutsky LA | title = Genital human papillomavirus infection in men: incidence and risk factors in a cohort of university students | journal = The Journal of Infectious Diseases | volume = 196 | issue = 8 | pages = 1128–36 | date = October 2007 | pmid = 17955430 | doi = 10.1086/521192 | doi-access = free }}{{update after|2015|5|4}}

Other studies analyzed urine, semen, and blood and found varying amounts of HPV, but there is not a publicly available test for those yet.

Although it is possible to test for HPV DNA in other kinds of infections, there are no FDA-approved tests for general screening in the United States{{cite web|url=https://www.cdc.gov/std/hpv/STDFact-HPV-and-men.htm|title=HPV and Men — CDC Fact Sheet|date=3 April 2008|website=Centers for Disease Control and Prevention|publisher=Centers for Disease Control and Prevention (CDC)|archive-url=https://web.archive.org/web/20091017213347/http://www.cdc.gov/std/hpv/stdfact-hpv-and-men.htm|archive-date=17 October 2009|url-status=live|access-date=13 November 2009}} or tests approved by the Canadian government,{{cite web |url=http://www.phac-aspc.gc.ca/std-mts/hpv-vph/hpv-vph-man-eng.php |title=Human Papillomavirus (HPV) and Men: Questions and Answers |access-date=10 September 2008 |year=2007 |quote=Currently, in Canada there is an HPV DNA test approved for women but not for men. |url-status=live |archive-url=https://web.archive.org/web/20080914045949/http://www.phac-aspc.gc.ca/std-mts/hpv-vph/hpv-vph-man-eng.php |archive-date=14 September 2008 }} since the testing is inconclusive and considered medically unnecessary.{{cite web |url=http://www.thehpvtest.com/HPV-for-men-FAQ.html#testmen |title=What Men Need to Know About HPV |access-date=4 April 2007 |year=2006 |quote=There is currently no FDA-approved test to detect HPV in men. That is because an effective, reliable way to collect a sample of male genital skin cells, which would allow detection of HPV, has yet to be developed. |archive-url=https://web.archive.org/web/20070407202850/http://www.thehpvtest.com/HPV-for-men-FAQ.html#testmen |archive-date=7 April 2007 }}

Genital warts are the only visible sign of low-risk genital HPV and can be identified with a visual check. These visible growths, however, are the result of non-carcinogenic HPV types. Five percent acetic acid (vinegar) is used to identify both warts and squamous intraepithelial neoplasia (SIL) lesions with limited success{{Citation needed|date=July 2012}} by causing abnormal tissue to appear white, but most doctors have found this technique helpful only in moist areas, such as the female genital tract.{{Citation needed|date=July 2012}} At this time, HPV tests for males are used only in research.{{Citation needed|date=July 2011}}

Research into testing for HPV by antibody presence has been done. The approach is looking for an immune response in blood, which would contain antibodies for HPV if the patient is HPV positive.{{cite journal | vauthors = Storey R, Joh J, Kwon A, Jenson AB, Ghim SJ, Kloecker GH | title = Detection of Immunoglobulin G against E7 of Human Papillomavirus in Non-Small-Cell Lung Cancer | journal = Journal of Oncology | volume = 2013 | page = 240164 | year = 2013 | pmid = 23533408 | pmc = 3603668 | doi = 10.1155/2013/240164 | doi-access = free }}{{cite journal | vauthors = Rocha-Zavaleta L, Ambrosio JP, de Lourdes Mora-Garcia M, Cruz-Talonia F, Hernandez-Montes J, Weiss-Steider B, Ortiz-Navarrete V, Monroy-Garcia A | title = Detection of antibodies against a human papillomavirus (HPV) type 16 peptide that differentiate high-risk from low-risk HPV-associated low-grade squamous intraepithelial lesions | journal = The Journal of General Virology | volume = 85 | issue = Pt 9 | pages = 2643–50 | date = September 2004 | pmid = 15302958 | doi = 10.1099/vir.0.80077-0 |doi-access=free}}{{cite journal | vauthors = Bolhassani A, Zahedifard F, Taslimi Y, Taghikhani M, Nahavandian B, Rafati S | title = Antibody detection against HPV16 E7 & GP96 fragments as biomarkers in cervical cancer patients | journal = The Indian Journal of Medical Research | volume = 130 | issue = 5 | pages = 533–41 | date = November 2009 | pmid = 20090101 | url = http://icmr.nic.in/ijmr/2009/november/1107.pdf | access-date = 18 March 2014 | archive-url = https://web.archive.org/web/20101216013119/http://icmr.nic.in/ijmr/2009/November/1107.pdf | archive-date = 16 December 2010 }}{{cite news|last=Fitzgerald|first=Kelly| title=Blood Test May Detect Sexually Transmitted Throat Cancer|url=http://www.medicalnewstoday.com/articles/262143.php|access-date=18 March 2014|newspaper=Medical News Today|date=18 June 2013|url-status=live|archive-url=https://web.archive.org/web/20140407012824/http://www.medicalnewstoday.com/articles/262143.php|archive-date=7 April 2014}} The reliability of such tests has not been proven, as there has not been a FDA approved product as of August 2018;{{Cite web|url=https://my.clevelandclinic.org/health/diseases/11901-hpv-human-papilloma-virus/diagnosis-and-tests|title=HPV (Human Papilloma Virus) Diagnosis and Tests|date=18 September 2018|website=Cleveland Clinic|access-date=8 February 2019|archive-date=1 August 2020|archive-url=https://web.archive.org/web/20200801180543/https://my.clevelandclinic.org/health/diseases/11901-hpv-human-papilloma-virus/diagnosis-and-tests}} testing by blood would be a less invasive test for screening purposes.

The HPV vaccines can prevent the most common types of infection. Cervical cancer screening, such as with the Papanicolaou test (pap) or looking at the cervix after using acetic acid, can detect early cancer or abnormal cells that may develop into cancer. Screening has reduced both the number and deaths from cervical cancer in the developed world. Warts can be removed by freezing.

{{Main|HPV vaccine}}

Three vaccines are available to prevent infection by some HPV types: Gardasil, Gardasil 9, and Cervarix; all three protect against initial infection with HPV types 16 and 18, which cause most of the HPV-associated cancer cases. Gardasil also protects against HPV types 6 and 11, which cause 90% of genital warts. Gardasil is a recombinant quadrivalent vaccine, whereas Cervarix is bivalent and is prepared from virus-like particles (VLP) of the L1 capsid protein. Gardasil 9 is nonavalent, having the potential to prevent about 90% of cervical, vulvar, vaginal, and anal cancers. It can protect for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; the latter five cause up to 20% of cervical cancers, which were not previously covered.{{cite web |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm426485.htm |title=FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV |website=Food and Drug Administration |date=10 December 2014 |access-date=8 March 2015 |archive-url=https://web.archive.org/web/20150110233107/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm426485.htm |archive-date=10 January 2015 }}

The vaccines provide little benefit to women already infected with HPV types 16 and 18.{{cite web|title=Human Papillomavirus Epidemiology and Prevention of Vaccine-Preventable Diseases|url=https://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html|work=CDC |access-date=30 January 2014|url-status=live|archive-url=https://web.archive.org/web/20140203022707/http://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html|archive-date=3 February 2014}} For this reason, the vaccine is recommended primarily for those women not yet having been exposed to HPV during sex. The World Health Organization position paper on HPV vaccination clearly outlines appropriate, cost-effective strategies for using the HPV vaccine in public sector programs.{{cite journal | title = Human papillomavirus vaccines. WHO position paper | journal = Relevé Épidémiologique Hebdomadaire | volume = 84 | issue = 15 | pages = 118–31 | date = April 2009 | pmid = 19360985 | url =https://www.who.int/wer/2009/wer8415.pdf | url-status = live | archive-url = https://web.archive.org/web/20101224093748/http://www.who.int/wer/2009/wer8415.pdf | archive-date = 24 December 2010 }}

There is high-certainty evidence that HPV vaccines protect against precancerous cervical lesions in young women, particularly those vaccinated aged 15 to 26.{{cite journal | vauthors = Koliopoulos G, Nyaga VN, Santesso N, Bryant A, Martin-Hirsch PP, Mustafa RA, Schünemann H, Paraskevaidis E, Arbyn M | title = Cytology versus HPV testing for cervical cancer screening in the general population | journal = The Cochrane Database of Systematic Reviews | volume = 8 | pages = CD008587 | date = August 2017 | issue = 7 | pmid = 28796882 | pmc = 6483676 | doi = 10.1002/14651858.CD008587.pub2 }} HPV vaccines do not increase the risk of serious adverse events. Longer follow-up is needed to monitor the impact of HPV vaccines on cervical cancer.

The CDC recommends the vaccines be delivered in two shots at an interval of at least 6 months for those aged 11–12, and three doses for those 13 and older.{{cite web|title=CDC recommends only two HPV shots for younger adolescents|url=https://www.cdc.gov/media/releases/2016/p1020-hpv-shots.html|website=Centers for Disease Control and Prevention|date=20 October 2016|access-date=24 March 2017|url-status=live|archive-url=https://web.archive.org/web/20170323234605/https://www.cdc.gov/media/releases/2016/p1020-hpv-shots.html|archive-date=23 March 2017}} In most countries, they are funded only for female use, but are approved for male use in many countries, and funded for teenage boys in Australia. The vaccine does not have any therapeutic effect on existing HPV infections or cervical lesions. In 2010, 49% of teenage girls in the US got the HPV vaccine.{{citation needed|date=February 2020}}

Following studies suggesting that the vaccine is more effective in younger girls{{cite journal | vauthors = Dobson SR, McNeil S, Dionne M, Dawar M, Ogilvie G, Krajden M, Sauvageau C, Scheifele DW, Kollmann TR, Halperin SA, Langley JM, Bettinger JA, Singer J, Money D, Miller D, Naus M, Marra F, Young E | title = Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial | journal = JAMA | volume = 309 | issue = 17 | pages = 1793–802 | date = May 2013 | pmid = 23632723 | doi = 10.1001/jama.2013.1625 | doi-access = free }} than in older teenagers, the United Kingdom, Switzerland, Mexico, the Netherlands, and Quebec began offering the vaccine in a two-dose schedule for girls aged under 15 in 2014.{{citation needed|date=May 2021}}

Cervical cancer screening recommendations have not changed for females who receive the HPV vaccine. It remains a recommendation that women continue cervical screening, such as Pap smear testing, even after receiving the vaccine, since it does not prevent all types of cervical cancer.{{cite journal | vauthors = Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER | title = Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP) | journal = MMWR. Recommendations and Reports | volume = 56 | issue = RR-2 | pages = 1–24 | date = March 2007 | pmid = 17380109 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm | url-status = live | archive-url = https://web.archive.org/web/20170520111925/https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm | archive-date = 20 May 2017 }}{{cite web|title=HPV Vaccine Information For Young Women|url=https://www.cdc.gov/std/hpv/stdfact-hpv-vaccine-young-women.htm|website=Centers for Disease Control and Prevention|date=3 January 2017|access-date=24 March 2017|url-status=live|archive-url=https://web.archive.org/web/20170325201535/https://www.cdc.gov/std/hpv/stdfact-hpv-vaccine-young-women.htm|archive-date=25 March 2017}}

Both men and women are carriers of HPV.{{cite web | url = http://www.webmd.com/sexual-conditions/hpv-genital-warts/hpv-virus-information-about-human-papillomavirus | title = HPV Virus: Information About Human Papillomavirus | website = WebMD | url-status = live | archive-url = https://web.archive.org/web/20080308164035/http://www.webmd.com/sexual-conditions/hpv-genital-warts/hpv-virus-information-about-human-papillomavirus | archive-date = 8 March 2008 }} The Gardasil vaccine also protects men against anal cancers and warts and genital warts.{{cite web |url=http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf |title=Gardasil patient information leaflet |date=April 2015 |access-date=11 July 2018 }}

The duration of both vaccines' efficacy has been observed since they were first developed, and is expected to be long-lasting.{{cite journal | vauthors = Deleré Y, Wichmann O, Klug SJ, van der Sande M, Terhardt M, Zepp F, Harder T | title = The efficacy and duration of vaccine protection against human papillomavirus: a systematic review and meta-analysis | journal = Deutsches Ärzteblatt International | volume = 111 | issue = 35–36 | pages = 584–91 | date = September 2014 | pmid = 25249360 | pmc = 4174682 | doi = 10.3238/arztebl.2014.0584 }}

In December 2014, the FDA approved a nine-valent Gardasil-based vaccine, Gardasil 9, to protect against infection with the four strains of HPV covered by the first generation of Gardasil as well as five other strains responsible for 20% of cervical cancers (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58).{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm426485.htm|type=press release|title=FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV|website=Food and Drug Administration|date=10 December 2014|access-date=28 February 2015|url-status=dead|archive-url=https://web.archive.org/web/20150110233107/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm426485.htm|archive-date=10 January 2015}}

The Centers for Disease Control and Prevention says that male "condom use may reduce the risk for genital human papillomavirus (HPV) infection" but provides a lesser degree of protection compared with other sexual transmitted infections "because HPV also may be transmitted by exposure to areas (e.g., infected skin or mucosal surfaces) that are not covered or protected by the condom."

{{cite web | publisher=Centers for Disease Control and Prevention (CDC) | url=https://www.cdc.gov/condomeffectiveness/latex.htm | title=CDC — Condom Effectiveness — Male Latex Condoms and Sexually Transmitted Diseases | date=22 October 2009 | access-date=23 October 2009 | url-status=live | archive-url=https://web.archive.org/web/20091017190441/http://www.cdc.gov/condomeffectiveness/latex.htm | archive-date=17 October 2009 }}

The virus is unusually hardy and is immune to most common disinfectants. It is the first virus ever shown to be resistant to inactivation by glutaraldehyde, which is among the most common strong disinfectants used in hospitals.{{cite journal | vauthors = Meyers J, Ryndock E, Conway MJ, Meyers C, Robison R | title = Susceptibility of high-risk human papillomavirus type 16 to clinical disinfectants | journal = The Journal of Antimicrobial Chemotherapy | volume = 69 | issue = 6 | pages = 1546–50 | date = June 2014 | pmid = 24500190 | pmc = 4019329 | doi = 10.1093/jac/dku006 }} Diluted sodium hypochlorite bleach is effective, but cannot be used on some types of re-usable equipment, such as ultrasound transducers.{{cite journal | vauthors = Miyague AH, Mauad FM, de Paula Martins W, Benedetti AC, Ferreira AE, Mauad-Filho F | title = Ultrasound scan as a potential source of nosocomial and crossinfection: a literature review | journal = Radiologia Brasileira | volume = 48 | issue = 5 | pages = 319–23 | date = 5 February 2019 | pmid = 26543284 | pmc = 4633077 | doi = 10.1590/0100-3984.2014.0002 }} As a result of these difficulties, there is developing concern about the possibility of transmitting the virus on healthcare equipment, particularly reusable gynecological equipment that cannot be autoclaved.{{cite journal | vauthors = Liu Z, Rashid T, Nyitray AG | title = Penises not required: a systematic review of the potential for human papillomavirus horizontal transmission that is non-sexual or does not include penile penetration | journal = Sexual Health | volume = 13 | issue = 1 | pages = 10–21 | date = February 2016 | pmid = 26433493 | doi = 10.1071/sh15089 | s2cid = 20937073 }}{{cite journal | vauthors = Sabeena S, Bhat P, Kamath V, Arunkumar G | title = Possible non-sexual modes of transmission of human papilloma virus | journal = The Journal of Obstetrics and Gynaecology Research | volume = 43 | issue = 3 | pages = 429–435 | date = March 2017 | pmid = 28165175 | doi = 10.1111/jog.13248 | s2cid = 39387099 | doi-access = free }} For such equipment, some health authorities encourage use of UV disinfection{{Cite report |author=HSE Quality Improvement Division — Decontamination Safety Programme |date=January 2017 |title=Health Service Executive Guidance for Decontamination of Semi-critical Ultrasound Probes; Semi-invasive and Non-invasive Ultrasound Probes |url=https://www.hse.ie/eng/about/who/qid/nationalsafetyprogrammes/decontamination/ultrasound-probe-decontamination-guidance-feb-17.pdf |id=QPSD-GL-028-1 |publisher=Department of Health United Kingdom |access-date=8 February 2019 |archive-date=1 August 2020 |archive-url=https://web.archive.org/web/20200801180834/https://www.hse.ie/eng/about/who/qid/nationalsafetyprogrammes/decontamination/ultrasound-probe-decontamination-guidance-feb-17.pdf }} or a non-hypochlorite "oxidizing‐based high‐level disinfectant [bleach] with label claims for non‐enveloped viruses",{{Cite web |website=Provincial Infection Control Network of British Columbia |date=2 June 2016 |title=Recommendations for Cleaning and Disinfection in Medical Ultrasound to Prevent Human Papillomavirus (HPV) Transmission |url=https://www.picnet.ca/wp-content/uploads/PICNet-Recommendations-for-Cleaning-and-Disinfection-in-Medical-Ultrasound.pdf}} such as a strong hydrogen peroxide solution{{Cite web |website=College of Physicians and Surgeons of British Columbia |date=December 2017|title=Reprocessing Requirements for Ultrasound Probes|url=https://www.cpsbc.ca/files/pdf/Reprocessing-Requirements-Ultrasound-Probes.pdf}} or chlorine dioxide wipes. Such disinfection methods are expected to be relatively effective against HPV.{{citation needed|date=May 2021}}

{{See also|Genital warts}}

There is currently no specific treatment for HPV infection.{{cite web | publisher = Centers for Disease Control and Prevention (CDC) | url = https://www.cdc.gov/std/HPV/STDFact-HPV.htm | title = Genital HPV Infection Fact Sheet | date = 10 April 2008 | access-date = 13 November 2009 | url-status = live | archive-url = https://web.archive.org/web/20120911095019/http://www.cdc.gov/STD/HPV/STDFact-HPV.htm | archive-date = 11 September 2012 }}

{{cite web |publisher = Centers for Disease Control and Prevention (CDC) |url = https://www.cdc.gov/std/hpv/STDFact-HPV-vaccine-young-women.htm |title = HPV Vaccine Information For Young Women |date = 26 June 2008 |access-date = 13 November 2009 |url-status = live |archive-url = https://web.archive.org/web/20091026150738/http://cdc.gov/std/hpv/STDFact-HPV-vaccine-young-women.htm |archive-date = 26 October 2009 }}{{cite web |url=https://www.cancer.org/docroot/cri/content/cri_2_4_2x_what_are_the_risk_factors_for_cervical_cancer_8.asp |title=What Are the Risk Factors for Cervical Cancer? |author=American Cancer Society |access-date=21 February 2008 |archive-url = https://web.archive.org/web/20080219151934/http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What_are_the_risk_factors_for_cervical_cancer_8.asp |archive-date = 19 February 2008}} However, the viral infection is usually cleared to undetectable levels by the immune system.{{cite web |url=http://www.webmd.com/sexual-conditions/hpv-genital-warts/hpv-treatment-is-there-hpv-cure |title=Cure for HPV |publisher=Webmd.com |access-date=29 August 2010 |url-status=live |archive-url=https://web.archive.org/web/20100818011132/http://www.webmd.com/sexual-conditions/hpv-genital-warts/hpv-treatment-is-there-hpv-cure |archive-date=18 August 2010 }} According to the Centers for Disease Control and Prevention, the body's immune system clears HPV naturally within two years for 90% of cases (see Clearance subsection in Virology for more detail). However, experts do not agree on whether the virus is eliminated or reduced to undetectable levels, and it is difficult to know when it is contagious.{{cite journal | vauthors = Gilbert LK, Alexander L, Grosshans JF, Jolley L | title = Answering frequently asked questions about HPV | journal = Sexually Transmitted Diseases | volume = 30 | issue = 3 | pages = 193–4 | date = March 2003 | pmid = 12616133 | doi = 10.1097/00007435-200303000-00002 | doi-access = free }}{{update inline|date=February 2021}}

Follow-up care is usually recommended and practiced by many health clinics.

{{cite web|title= Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis.|publisher= Centers for Disease Control and Prevention|url= http://stacks.cdc.gov/view/cdc/20711|access-date= 23 October 2015|url-status= live|archive-url= https://web.archive.org/web/20151116064628/http://stacks.cdc.gov/view/cdc/20711|archive-date= 16 November 2015| vauthors = Kuhar DT, Henderson DK, Struble KA, Heneine W, Thomas V, Cheever LW, Gomaa A, Panlilio AL }} Follow-up is sometimes not successful because a portion of those treated do not return to be evaluated. In addition to the normal methods of phone calls and mail, text messaging and email can improve the number of people who return for care.{{cite journal | vauthors = Desai M, Woodhall SC, Nardone A, Burns F, Mercey D, Gilson R | title = Active recall to increase HIV and STI testing: a systematic review | journal = Sexually Transmitted Infections | volume = 91 | issue = 5 | pages = 314–23 | date = August 2015 | pmid = 25759476 | doi = 10.1136/sextrans-2014-051930 | s2cid = 663971 | doi-access = free }} As of 2015 it is unclear the best method of follow up following treatment of cervical intraepithelial neoplasia.{{cite journal | vauthors = van der Heijden E, Lopes AD, Bryant A, Bekkers R, Galaal K | title = Follow-up strategies after treatment (large loop excision of the transformation zone (LLETZ)) for cervical intraepithelial neoplasia (CIN): Impact of human papillomavirus (HPV) test | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD010757 | date = January 2015 | issue = 1 | pmid = 25562623 | pmc = 6457759 | doi = 10.1002/14651858.cd010757.pub2 }}

Globally, 12% of women are positive for HPV DNA, with rates varying by age and country. The highest rates of HPV are in younger women, with a rate of 24% in women under 25 years.{{cite journal | vauthors = Serrano B, Brotons M, Bosch FX, Bruni L | title = Epidemiology and burden of HPV-related disease | journal = Best Practice & Research. Clinical Obstetrics & Gynaecology | volume = 47 | pages = 14–26 | date = February 2018 | pmid = 29037457 | doi = 10.1016/j.bpobgyn.2017.08.006 | series = Human Papilloma Virus in Gynaecology }} Rates decline in older age groups in Europe and the Americas, but less so in Africa and Asia. The rates are highest in Sub-Saharan Africa (24%) and Eastern Europe (21%) and lowest in North America (5%) and Western Asia (2%).{{cite journal | vauthors = Chan CK, Aimagambetova G, Ukybassova T, Kongrtay K, Azizan A | title = Human Papillomavirus Infection and Cervical Cancer: Epidemiology, Screening, and Vaccination-Review of Current Perspectives | journal = Journal of Oncology | volume = 2019 | page = 3257939 | date = 10 October 2019 | pmid = 31687023 | pmc = 6811952 | doi = 10.1155/2019/3257939 | doi-access = free }}

The most common types of HPV worldwide are HPV16 (3.2%), HPV18 (1.4%), HPV52 (0.9%), HPV31 (0.8%), and HPV58 (0.7%). High-risk types of HPV are also distributed unevenly, with HPV16 having a rate of around 13% in Africa and 30% in West and Central Asia.

Like many diseases, HPV disproportionately affects low-income and resource-poor countries. The higher rates of HPV in Sub-Saharan Africa, for example, may be related to high exposure to human immunodeficiency virus (HIV) in the region. Other factors that impact the global spread of the disease are sexual behavior, including age of sexual debut and number of sexual partners, and ease of access to barrier contraception, all of which vary globally.{{cite journal | vauthors = Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, Vignat J, Ferlay J, Bray F, Plummer M, Franceschi S | title = Global burden of human papillomavirus and related diseases | journal = Vaccine | volume = 30 | pages = F12-23 | date = November 2012 | pmid = 23199955 | doi = 10.1016/j.vaccine.2012.07.055 | series = Comprehensive Control of HPV Infections and Related Diseases| issue = Suppl 5 | s2cid = 30694437 | url = https://www.openaccessrepository.it/record/22484 | archive-url = https://web.archive.org/web/20200529065805/https://www.openaccessrepository.it/record/22484 | url-status = dead | archive-date = 29 May 2020 | url-access = subscription }}

The papilloma virus is not only widespread among women, but is also behind most cases of oropharyngeal cancer, which is the fastest growing cancer among young adults in Western countries. Moreover, as of 2025, papillomavirus is the most prevalent sexually transmitted infection in the world.{{cite web|access-date=21 March 2025 |language=it |location=Milan |title=Tumori orofaringeo da HPV:ecco il primo test per la diagnosi precoce |url=https://www.ieo.it/it/PNA/Lista-News/TUMORI-OROFARINGEI-DA-HPV-ECCO-IL-PRIMO-TEST-PER-LA-DIAGNOSI-PRECOCE/ |website=European Institute of Oncology}}

HPV is estimated to be the most common sexually transmitted infection in the United States. Most sexually active men and women will probably acquire genital HPV infection at some point in their lives.{{cite journal | vauthors = Baseman JG, Koutsky LA | title = The epidemiology of human papillomavirus infections | journal = Journal of Clinical Virology | volume = 32 | issue = Suppl 1 | pages = S16-24 | date = March 2005 | pmid = 15753008 | doi = 10.1016/j.jcv.2004.12.008 | quote = Overall, these DNA-based studies, combined with measurements of type-specific antibodies against HPV capsid antigens, have shown that most (>50%) sexually active women have been infected by one or more genital HPV types at some point in time [S17]. | doi-access = free }} The American Social Health Association estimates that about 75–80% of sexually active Americans will be infected with HPV at some point in their lifetime.{{cite web |url= http://www.ashastd.org/hpv/hpv_learn_men.cfm |title= American Social Health Association — HPV Resource Center |access-date= 17 August 2007 |archive-url= https://web.archive.org/web/20070718164248/http://www.ashastd.org/hpv/hpv_learn_men.cfm |archive-date= 18 July 2007 }}{{cite web | url= http://www.ashastd.org/hpv/hpv_learn_patfactsheet.cfm | title= American Social Health Association — National HPV and Cervical Cancer Prevention Resource Center | access-date= 1 July 2008 | archive-url= https://web.archive.org/web/20080619005506/http://www.ashastd.org/hpv/hpv_learn_patfactsheet.cfm | archive-date= 19 June 2008 }} By the age of 50 more than 80% of American women will have contracted at least one strain of genital HPV.{{cite journal | vauthors = Dunne EF, Unger ER, Sternberg M, McQuillan G, Swan DC, Patel SS, Markowitz LE | title = Prevalence of HPV infection among females in the United States | journal = JAMA | volume = 297 | issue = 8 | pages = 813–9 | date = February 2007 | pmid = 17327523 | doi = 10.1001/jama.297.8.813 | doi-access = free }}{{Citation | title = STD, HIV | contribution = HPV vaccine report | contribution-url = http://www.plannedparenthood.org/issues-action/std-hiv/hpv-vaccine/reports/HPV-6359.htm | publisher = Planned Parenthood | quote = In fact, the lifetime risk for contracting HPV is at least 50 percent for all sexually active women and men, and, it is estimated that, by the age of 50, at least 80 percent of women will have acquired sexually transmitted HPV (CDC, 2004; CDC, 2006). | access-date = 12 February 2009 | archive-date = 25 April 2009 | archive-url = https://web.archive.org/web/20090425184948/http://www.plannedparenthood.org/issues-action/std-hiv/HPV-vaccine/reports/HPV-6359.htm }} It was estimated that, in the year 2000, there were approximately 6.2 million new HPV infections among Americans aged 15–44; of these, an estimated 74% occurred to people between ages of 15 and 24.{{cite journal | vauthors = Weinstock H, Berman S, Cates W | title = Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000 | journal = Perspectives on Sexual and Reproductive Health | volume = 36 | issue = 1 | pages = 6–10 | date = January–February 2004 | pmid = 14982671 | doi = 10.1363/3600604 | url = http://www.guttmacher.org/pubs/journals/3600604.html | url-status = live | archive-url = https://web.archive.org/web/20080704215120/http://www.guttmacher.org/pubs/journals/3600604.html | archive-date = 4 July 2008 | doi-access = free }} Of the STIs studied, genital HPV was the most commonly acquired. In the United States, it is estimated that 10% of the population has an active HPV infection, 4% has an infection that has caused cytological abnormalities, and an additional 1% has an infection causing genital warts.{{cite journal | vauthors = Koutsky L | title = Epidemiology of genital human papillomavirus infection | journal = The American Journal of Medicine | volume = 102 | issue = 5A | pages = 3–8 | date = May 1997 | pmid = 9217656 | doi = 10.1016/s0002-9343(97)00177-0 }}

Estimates of HPV prevalence vary from 14% to more than 90%.{{cite journal | vauthors = Revzina NV, Diclemente RJ | title = Prevalence and incidence of human papillomavirus infection in women in the USA: a systematic review | journal = International Journal of STD & AIDS | volume = 16 | issue = 8 | pages = 528–37 | date = August 2005 | pmid = 16105186 | doi = 10.1258/0956462054679214 | s2cid = 23728417 | quote = The prevalence of HPV reported in the assessed studies ranged from 14% to more than 90%. }} One reason for the difference is that some studies report women who currently have a detectable infection, while other studies report women who have ever had a detectable infection.{{cite news | first = Marie | last = McCullough | title = Cancer-virus strains rarer than first estimated | url = http://www.philly.com/mld/inquirer/living/health/16798039.htm | work = The Philadelphia Inquirer | date = 28 February 2007| access-date = 2 March 2007 |archive-url = https://web.archive.org/web/20070310030819/http://www.philly.com/mld/inquirer/living/health/16798039.htm |archive-date = 10 March 2007}}{{cite news | first = David | last = Brown | title = Study finds more women than expected have HPV | url = http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2007/02/28/MNGOCOCAF61.DTL | work = San Francisco Chronicle | date = 28 February 2007 | access-date = 2 March 2007 | orig-date = The Washington Post, "More American Women Have HPV Than Previously Thought" | url-status = live | archive-url = https://web.archive.org/web/20071109234438/http://www.sfgate.com/cgi-bin/article.cgi?f=%2Fc%2Fa%2F2007%2F02%2F28%2FMNGOCOCAF61.DTL | archive-date = 9 November 2007 }} Another cause of discrepancy is the difference in strains that were tested for.{{citation needed|date=May 2021}}

One study found that, during 2003–2004, at any given time, 26.8% of women aged 14 to 59 were infected with at least one type of HPV. This was higher than previous estimates; 15.2% were infected with one or more of the high-risk types that can cause cancer.{{cite news | url = http://www.newsvine.com/_news/2008/03/11/1358811-study-finds-1-in-4-us-teens-has-a-std | title = Study Finds 1 in 4 US Teens Has a STD | work = Newsvine | agency = Associated Press | first = Lindsey | last = Tanner | date = 11 March 2008 | access-date = 17 March 2008 | archive-url = https://web.archive.org/web/20080316031331/http://www.newsvine.com/_news/2008/03/11/1358811-study-finds-1-in-4-us-teens-has-a-std | archive-date = 16 March 2008 }}

The prevalence of high-risk and low-risk types is roughly similar over time.

Human papillomavirus is not included among the diseases that are typically reportable to the CDC as of 2011.{{cite web | title = MMWR: Summary of Notifiable Diseases | url = https://www.cdc.gov/mmwr/mmwr_nd/ | publisher = CDC | work = Morbidity and Mortality Weekly Report | access-date = 18 August 2014 | url-status = live | archive-url = https://web.archive.org/web/20140817021902/http://www.cdc.gov/mmwr/mmwr_nd/ | archive-date = 17 August 2014 }}[https://www.nlm.nih.gov/medlineplus/ency/article/001929.htm Reportable diseases] {{webarchive|url=https://web.archive.org/web/20160412095010/https://www.nlm.nih.gov/medlineplus/ency/article/001929.htm |date=12 April 2016 }}, from MedlinePlus, a service of the U.S. National Library of Medicine, from the National Institutes of Health. Update: 19 May 2013 by Jatin M. Vyas. Also reviewed by David Zieve.

On average, 538 cases of HPV-associated cancers were diagnosed per year in Ireland during the period 2010 to 2014.{{Cite web|url=https://www.hiqa.ie/sites/default/files/2018-12/HTA-for-HPV-Vaccination-boys.pdf|title=Health Information Quality Authority (HIQA)}} Cervical cancer was the most frequent HPV-associated cancer with on average 292 cases per year (74% of the female total, and 54% of the overall total of HPV-associated cancers). A study of 996 cervical cytology samples in an Irish urban female, opportunistically screened population, found an overall HPV prevalence of 19.8%, HPV 16 at 20% and HPV 18 at 12% were the commonest high-risk types detected. In Europe, types 16 and 18 are responsible for over 70% of cervical cancers.{{Cite web|url=https://www.hse.ie/eng/health/immunisation/hcpinfo/guidelines/chapter10.pdf|title=HSE vaccination guidelines}} Overall rates of HPV-associated invasive cancers may be increasing. Between 1994 and 2014, there was a 2% increase in the rate of HPV-associated invasive cancers per year for both sexes in Ireland.

As HPV is known to be associated with anogenital warts, these are notifiable to the Health Protection Surveillance Centre (HPSC). Genital warts are the second most common STI in Ireland.{{Cite web|url=https://www.hivireland.ie/hepatitis-and-stis/stis/sti-statistics/|title=STI Statistics – HIV Ireland|access-date=11 January 2019}} There were 1,281 cases of anogenital warts notified in 2017, which was a decrease on the 2016 figure of 1,593.{{Cite web | title = Ano-genital warts in Ireland, 2017 | work = Annual Epidemiological Report | date = October 2018 | url = http://www.hpsc.ie/a-z/hivstis/sexuallytransmittedinfections/ano-genitalwarts/surveillancereports/Ano-genital%20warts%20in%20Ireland%202017%20(includes%20latest%20trends).pdf | publisher = HSE Health Protection Surveillance Centre | access-date = 11 January 2019 | archive-url = https://web.archive.org/web/20190111232645/http://www.hpsc.ie/a-z/hivstis/sexuallytransmittedinfections/ano-genitalwarts/surveillancereports/Ano-genital%20warts%20in%20Ireland%202017%20(includes%20latest%20trends).pdf | archive-date = 11 January 2019 }} The highest age-specific rate for both male and female was in the 25–29 year old age range; 53% of cases were among males.

In Sri Lanka, the prevalence of HPV is 15.5% regardless of cytological abnormalities.{{cite journal | vauthors = Shanaka KA, Wilathgamuwa S, Gunawardene YI, Dassanayake RS | title = Prevalence of human papilloma virus and their high-risk genotypes in Sri Lankan women | journal = VirusDisease | volume = 29 | issue = 1 | pages = 27–31 | date = March 2018 | pmid = 29607355 | pmc = 5877853 | doi = 10.1007/s13337-018-0419-7 }}

In the Autonomous Region of Inner Mongolia, overall HPV prevalence is 14.5% but shows substantial ethnical disparity, the prevalence in Mongolian women (14.9%) being much higher than that of Han participants (4.3%).{{cite journal | vauthors = Wang X, Ji Y, Li J, Dong H, Zhu B, Zhou Y, Wang J, Zhou X, Wang Y, Peppelenbosch MP, Pan Q, Ji X, Liu D | title = Prevalence of human papillomavirus infection in women in the Autonomous Region of Inner Mongolia: A population-based study of a Chinese ethnic minority | journal = J Med Virol | volume = 90 | issue = 1 | pages = 148–156 | date = January 2018 | pmid = 28661048 | doi = 10.1002/jmv.24888 | s2cid = 24613222 }} Urbanization, the number of sex partners, and PAP history appear as risk factors for HPV infection in Han, but not in Mongolian women. The region is thus an important example that the epidemiology of HPV is more related to cultural and ethnical factors and not to geography per se.{{citation needed|date=November 2022}}

One of the first studies linking the risk of uterine carcinoma with the number of sexual activities was performed in 1842, in Verona. Dr. Domenico Rigoni-Stern observed that uterine cancer incidence among Catholic nuns living in convents in the countryside was lower than in women living in the city. Highest incidence was seen for prostitutes, thereby linking uterine cancer prevalence to the number of sexual partners, and suggesting that this disease might have a sexually transmissible component.{{Cite journal |last=DiMaio |first=Daniel |date=1 June 2015 |title=Nuns, Warts, Viruses, and Cancer |url=https://www.pmc.ncbi.nlm.nih.gov/articles/PMC4445434/ |journal=The Yale Journal of Biology and Medicine |language=en |volume=88 |issue=2 |pages=127–129 |pmid=26029011 |pmc=4445434 |archive-url=https://web.archive.org/web/20250217062822/https://pmc.ncbi.nlm.nih.gov/articles/PMC4445434/ |archive-date=17 February 2025 |access-date=9 March 2025 |url-status=live }}

In 1972, the association of the human papillomaviruses with skin cancer in epidermodysplasia verruciformis was proposed by Stefania Jabłońska in Poland. In 1976, Harald zur Hausen published the hypothesis that human papillomavirus plays an important role in the cause of cervical cancer. In 1978, Jabłońska and Gerard Orth at the Pasteur Institute discovered HPV-5 in skin cancer.{{cite book | title = Human papillomaviruses | year = 2007 | publisher = World Health Organization, International Agency for Research on Cancer | isbn = 978-92-832-1290-4 | url-access = registration | url = https://archive.org/details/humanpapillomavi0000publ/page/36/mode/1up |page=36|access-date=7 September 2020}} In 1983 and 1984 zur Hausen and his collaborators identified HPV16 and HPV18 in cervical cancer.{{cite web | url= http://soundprint.org/radio/display_show/ID/774/name/HPV+-+the+Shy+Virus | title= HPV — the Shy Virus | date= 6 December 2008 | access-date= 6 December 2008 | publisher= Sound print | type= radio program | url-status= live | archive-url= https://web.archive.org/web/20090328142100/http://www.soundprint.org/radio/display_show/ID/774/name/HPV+-+the+Shy+Virus | archive-date= 28 March 2009 }}

The HeLa cell line contains extra DNA in its genome that originated from HPV type 18.{{cite journal | vauthors = Picken RN, Yang HL | title = The integration of HPV-18 into HeLa cells has involved duplication of part of the viral genome as well as human DNA flanking sequences | journal = Nucleic Acids Research | volume = 15 | issue = 23 | page = 10068 | date = December 1987 | pmid = 2827110 | pmc = 306572 | doi = 10.1093/nar/15.23.10068 }}

The Ludwig-McGill HPV Cohort is one of the world's largest longitudinal studies of the natural history of human papillomavirus (HPV) infection and cervical cancer risk. It was established in 1993 by Ludwig Cancer Research and McGill University in Montreal, Canada.{{Cite journal |last1=Franco |first1=E. |last2=Villa |first2=L. |last3=Rohan |first3=T. |last4=Ferenczy |first4=A. |last5=Petzl-Erler |first5=M. |author-link5=Maria Luiza Petzl-Erler |last6=Matlashewski |first6=G. |year=1999 |title=Design and methods of the Ludwig-McGill longitudinal study of the natural history of human papillomavirus infection and cervical neoplasia in Brazil. Ludwig-McGill Study Group - PubMed |journal=Revista Panamericana de Salud Pública |volume=6 |issue=4 |pages=223–233 |doi=10.1590/s1020-49891999000900001 |pmid=10572472 |doi-access=free}}

{{Reflist}}

• {{Cite journal |last1=Nelson |first1=Chase W. |last2=Mirabello |first2=Lisa |date=1 June 2023 |title=Human papillomavirus genomics: Understanding carcinogenicity |journal=Tumour Virus Research |volume=15 |pages=200258 |doi=10.1016/j.tvr.2023.200258 |issn=2666-6790 |pmc=10063409 |pmid=36812987}}

• {{Cite journal |last1=Hoppe-Seyler |first1=Karin |last2=Bossler |first2=Felicitas |last3=Braun |first3=Julia A. |last4=Herrmann |first4=Anja L. |last5=Hoppe-Seyler |first5=Felix |date=1 February 2018 |title=The HPV E6/E7 Oncogenes: Key Factors for Viral Carcinogenesis and Therapeutic Targets |url=https://linkinghub.elsevier.com/retrieve/pii/S0966842X17301774 |journal=Trends in Microbiology |language=English |volume=26 |issue=2 |pages=158–168 |doi=10.1016/j.tim.2017.07.007 |issn=0966-842X |pmid=28823569|url-access=subscription }}

• [https://hpvcentre.net/ Information Centre on HPV and Cancer] – ICO
• [https://www.cdc.gov/sti/about/about-genital-hpv-infection.html HPV Fact sheets] at the Centers for Disease Control and Prevention
• [https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/vaccine-preventable-diseases-key-facts/human-papillomavirus-hpv "Human papillomavirus (HPV)"] European Medicines Agencyq (EMA)
• [https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-vaccine-fact-sheet "Human Papillomavirus (HPV) Vaccines"], National Cancer Institute

{{Medical condition classification and resources

| DiseasesDB = 6032

| ICD10 = {{ICD10|B|97|7|b|95}}

| ICD9 = {{ICD9|078.1}} {{ICD9|079.4}}

| ICDO =

| OMIM =

| MedlinePlus =

| eMedicineSubj = med

| eMedicineTopic = 1037

| MeshID = D030361}}

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