cervical cancer#Staging

The early stages of cervical cancer may be completely free of symptoms. Vaginal bleeding, contact bleeding (one most common form being bleeding after sexual intercourse), or (rarely) a vaginal mass may indicate the presence of cervical cancer. Also, moderate pain during sexual intercourse and vaginal discharge are symptoms of cervical cancer.{{cite web|url=https://www.medicinenet.com/cervical_cancer/article.htm#what_is_cervical_cancer|title=Cervical Cancer Symptoms, Signs, Causes, Stages & Treatment|website=medicinenet.com}} Bleeding after douching or after a pelvic exam is a common symptom of cervical cancer.{{Cite news| url=http://www.cancer.org/cancer/cervicalcancer/moreinformation/cervicalcancerpreventionandearlydetection/cervical-cancer-prevention-and-early-detection-cervical-cancer-signs-and-symptoms| title=Cervical Cancer Prevention and Early Detection| work=Cancer| archive-url=https://web.archive.org/web/20150710000534/http://www.cancer.org/cancer/cervicalcancer/moreinformation/cervicalcancerpreventionandearlydetection/cervical-cancer-prevention-and-early-detection-cervical-cancer-signs-and-symptoms| archive-date=10 July 2015| url-status=live}} In advanced disease, metastases may be present in the abdomen, lungs, or elsewhere.{{cite journal | vauthors = Li H, Wu X, Cheng X | title = Advances in diagnosis and treatment of metastatic cervical cancer | journal = Journal of Gynecologic Oncology | volume = 27 | issue = 4 | pages = e43 | date = July 2016 | pmid = 27171673 | pmc = 4864519 | doi = 10.3802/jgo.2016.27.e43 }}

Symptoms of advanced cervical cancer may include loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, swollen legs, heavy vaginal bleeding, bone fractures, and (rarely) leakage of urine or faeces from the vagina.{{cite encyclopedia |url=https://www.nlm.nih.gov/medlineplus/ency/article/000893.htm |title=Cervical cancer |access-date=2 December 2007 |date=9 June 2006 |encyclopedia=MedlinePlus Medical Encyclopedia |publisher=National Institutes of Health |url-status=live |archive-url=https://web.archive.org/web/20071011011822/http://www.nlm.nih.gov/medlineplus/ency/article/000893.htm |archive-date=11 October 2007 }} Other signs of locally advanced disease (as the cancer invades organs in the pelvis) include hydronephrosis with flank pain as the ureters directing urine from the kidneys to bladder are blocked, leg swelling and blood clots in the legs as pelvic veins are blocked, rectal bleeding, and bleeding in the urine.

File:Figure 28 02 08.JPG

File:Figure 28 02 06.JPG

Infection with some types of HPV is the greatest risk factor for cervical cancer, followed by smoking.{{cite journal |vauthors= Gadducci A, Barsotti C, Cosio S, Domenici L, Riccardo Genazzani A |title=Smoking habit, immune suppression, oral contraceptive use, and hormone replacement therapy use and cervical carcinogenesis: a review of the literature |journal=Gynecological Endocrinology |volume=27 |issue=8 |pages=597–604 |date=August 2011 |pmid=21438669 |doi=10.3109/09513590.2011.558953 |s2cid=25447563 }} HIV infection is also a risk factor. Not all of the causes of cervical cancer are known, however, and several other contributing factors have been implicated.{{cite book |title=Gynaecology by Ten Teachers | vauthors = Campbell S, Monga A |edition=18th |year=2006 |publisher=Hodder Education |isbn=978-0-340-81662-2 |url-access=registration |url=https://archive.org/details/gynaecology0000unse }}{{cite web|url=https://www.medicinenet.com/cervical_cancer/article.htm#cervical_cancer_facts|title=Cervical Cancer Symptoms, Signs, Causes, Stages & Treatment|website=medicinenet.com}}

Infection with HPV is generally believed to be required for cervical cancer to occur.{{cite journal | vauthors = Snijders PJ, Steenbergen RD, Heideman DA, Meijer CJ | title = HPV-mediated cervical carcinogenesis: concepts and clinical implications | journal = The Journal of Pathology | volume = 208 | issue = 2 | pages = 152–164 | date = January 2006 | pmid = 16362994 | doi = 10.1002/path.1866 | s2cid = 25400770 | doi-access = free }} HPV types 16 and 18 are the cause of 75% of cervical cancer cases globally, while 31 and 45 are the causes of another 10%.{{cite book| veditors = Dillman RK, Oldham RO |title=Principles of cancer biotherapy |year=2009 |publisher=Springer |location=Dordrecht|isbn=978-90-481-2289-9|page=149|url=https://books.google.com/books?id=emGC_fRJH_IC&pg=PA149|edition=5th |url-status=live|archive-url=https://web.archive.org/web/20151029195259/https://books.google.com/books?id=emGC_fRJH_IC&pg=PA149|archive-date=29 October 2015}}

Women who have multiple sexual partners, or have partners who have multiple sexual partners, regardless of sex are at higher risk of cervical cancer.{{cite web|url=http://www.cancer.org/docroot/CRI/content/CRI_2_2_2X_What_causes_cancer_of_the_cervix_Can_it_be_prevented_8.asp?sitearea= |title=What Causes Cancer of the Cervix? |access-date=2 December 2007 |date=30 November 2006 |publisher=American Cancer Society |archive-url = https://web.archive.org/web/20071013160516/http://cancer.org/docroot/CRI/content/CRI_2_2_2X_What_causes_cancer_of_the_cervix_Can_it_be_prevented_8.asp?sitearea= |archive-date = 13 October 2007}}{{cite journal | vauthors = Marrazzo JM, Koutsky LA, Kiviat NB, Kuypers JM, Stine K | title = Papanicolaou test screening and prevalence of genital human papillomavirus among women who have sex with women | journal = American Journal of Public Health | volume = 91 | issue = 6 | pages = 947–952 | date = June 2001 | pmid = 11392939 | pmc = 1446473 | doi = 10.2105/AJPH.91.6.947 }}

Over 200 types of HPV known,{{Cite web |date=2019-03-01 |title=HPV and Cancer - NCI |url=https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-and-cancer |access-date=2024-02-13 |website=www.cancer.gov |language=en}} 12 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), three as probable high-risk (26, 53, and 66), and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108).{{cite journal |vauthors = Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, Snijders PJ, Meijer CJ |display-authors = 6 |title = Epidemiologic classification of human papillomavirus types associated with cervical cancer |journal = The New England Journal of Medicine |volume = 348 |issue = 6 |pages = 518–527 |date = February 2003 |pmid = 12571259 |doi = 10.1056/NEJMoa021641 |hdl-access = free |hdl = 2445/122831 |s2cid = 1451343 |url = https://revistasojs.ucaldas.edu.co/index.php/hacialapromociondelasalud/article/view/2173 }} Most cases of squamous cell carcinomas of the cervix are due to HPV type 16 and most cases of adenocarcinoma are due to HPV type 18. High risk HPV viral subtypes can integrate their DNA into the host genome and induce transcription of the viral cancer causing proteins E6 and E7.{{cite journal |last1=Peng |first1=Qiu |last2=Wang |first2=Lujuan |last3=Zuo |first3=Liang |last4=Gao |first4=Shuichao |last5=Jiang |first5=Xianjie |last6=Han |first6=Yaqian |last7=Lin |first7=Jinguan |last8=Peng |first8=Mingjing |last9=Wu |first9=Nayiyuan |last10=Tang |first10=Yanyan |last11=Tian |first11=Hao |last12=Zhou |first12=Yujuan |last13=Liao |first13=Qianjin |title=HPV E6/E7: insights into their regulatory role and mechanism in signaling pathways in HPV-associated tumor |journal=Cancer Gene Therapy |date=January 2024 |volume=31 |issue=1 |pages=9–17 |doi=10.1038/s41417-023-00682-3}} E6 degrades the tumor suppressing protein p53 and E7 degrades and inactivates the tumor suppressing protein pRb. The loss of p53 and pRb leads to increased blood vessel growth feeding tumors (via vascular endothelial growth factor(VEGF) over-expression), loss of tumor cell suppression and cell cycle regulation disruptions all of which can lead to cervical cancer.

Genital warts, which are a form of benign tumor of epithelial cells, are also caused by various strains of HPV. However, these serotypes are usually not related to cervical cancer. Having multiple strains at the same time is common, including those that can cause cervical cancer along with those that cause warts.

File:RICO tobacco litigation corrective statement, Whitehall, PA (cropped).jpg corrective statement: "Smoking also causes reduced fertility, low birth weight in newborns, and cancer of the cervix" (United States, 2024).]]

Cigarette smoking, both active and passive, increases the risk of cervical cancer. Among HPV-infected women, current and former smokers have roughly two to three times the incidence of invasive cancer. Passive smoking is also associated with increased risk but to a lesser extent.{{cite web | publisher = National Cancer Institute, National Institutes of Health | work = PDQ | url = http://cancer.gov/cancertopics/pdq/prevention/cervical/HealthProfessional | title = Cervical Cancer Prevention | date = 26 December 2022 | location = Bethesda, MD }}

Smoking has also been linked to the development of cervical cancer.{{cite journal |vauthors = Luhn P, Walker J, Schiffman M, Zuna RE, Dunn ST, Gold MA, Smith K, Mathews C, Allen RA, Zhang R, Wang S, Wentzensen N |display-authors = 6 |title = The role of co-factors in the progression from human papillomavirus infection to cervical cancer |journal = Gynecologic Oncology |volume = 128 |issue = 2 |pages = 265–270 |date = February 2013 |pmid = 23146688 |pmc = 4627848 |doi = 10.1016/j.ygyno.2012.11.003 }}{{cite journal | vauthors = Remschmidt C, Kaufmann AM, Hagemann I, Vartazarova E, Wichmann O, Deleré Y | title = Risk factors for cervical human papillomavirus infection and high-grade intraepithelial lesion in women aged 20 to 31 years in Germany | journal = International Journal of Gynecological Cancer | volume = 23 | issue = 3 | pages = 519–526 | date = March 2013 | pmid = 23360813 | doi = 10.1097/IGC.0b013e318285a4b2 | s2cid = 205679729 | doi-access = free }} Smoking can increase the risk in women a few different ways, which can be by direct and indirect methods of inducing cervical cancer.{{cite journal | vauthors = Agorastos T, Miliaras D, Lambropoulos AF, Chrisafi S, Kotsis A, Manthos A, Bontis J | title = Detection and typing of human papillomavirus DNA in uterine cervices with coexistent grade I and grade III intraepithelial neoplasia: biologic progression or independent lesions? | journal = European Journal of Obstetrics, Gynecology, and Reproductive Biology | volume = 121 | issue = 1 | pages = 99–103 | date = July 2005 | pmid = 15949888 | doi = 10.1016/j.ejogrb.2004.11.024 }} A direct way of contracting this cancer is a smoker has a higher chance of cervical intraepithelial neoplasia (CIN3) occurring, which has the potential of forming cervical cancer. When CIN3 lesions lead to cancer, most of them have the assistance of the HPV virus, but that is not always the case, which is why it can be considered a direct link to cervical cancer. Heavy smoking and long-term smoking seem to have more of a risk of getting the CIN3 lesions than lighter smoking or not smoking at all.{{cite journal | vauthors = Jensen KE, Schmiedel S, Frederiksen K, Norrild B, Iftner T, Kjær SK | title = Risk for cervical intraepithelial neoplasia grade 3 or worse in relation to smoking among women with persistent human papillomavirus infection | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 21 | issue = 11 | pages = 1949–1955 | date = November 2012 | pmid = 23019238 | pmc = 3970163 | doi = 10.1158/1055-9965.EPI-12-0663 }} Although smoking has been linked to cervical cancer, it aids in the development of HPV, which is the leading cause of this type of cancer. Also, not only does it aid in the development of HPV, but also if the woman is already HPV-positive, she is at an even greater likelihood of contracting cervical cancer.

Long-term use of oral contraceptives is associated with increased risk of cervical cancer in women who have had HPV. Women who have used oral contraceptives for 5 to 9 years have about three times the incidence of invasive cancer, and those who used them for 10 years or longer have about four times the risk.{{cite journal | vauthors = Asthana S, Busa V, Labani S | title = Oral contraceptives use and risk of cervical cancer-A systematic review & meta-analysis | journal = European Journal of Obstetrics, Gynecology, and Reproductive Biology | volume = 247 | pages = 163–175 | date = April 2020 | pmid = 32114321 | doi = 10.1016/j.ejogrb.2020.02.014 | s2cid = 211728228 }}

Having many pregnancies is associated with an increased risk of cervical cancer. Among HPV-infected women, those who have had seven or more full-term pregnancies have around four times the risk of cancer compared with women with no pregnancies, and two to three times the risk of women who have had one or two full-term pregnancies.

File:Ca cervicis uteri T2 SAG.jpg

The Pap test can be used as a screening test but produces a false negative in up to 50% of cases of cervical cancer.Cecil Medicine: Expert Consult Premium Edition. {{ISBN|1-4377-3608-4}}, 9781437736083. Page 1317.Berek and Hacker's Gynecologic Oncology. {{ISBN|0-7817-9512-5}}, 9780781795128. Page 342 Another concern is the cost of doing Pap tests, which makes them unaffordable in many areas of the world.{{cite journal | vauthors = Cronjé HS | title = Screening for cervical cancer in developing countries | journal = International Journal of Gynaecology and Obstetrics | volume = 84 | issue = 2 | pages = 101–108 | date = February 2004 | pmid = 14871510 | doi = 10.1016/j.ijgo.2003.09.009 | s2cid = 21356776 }}

Confirmation of the diagnosis of cervical cancer or precancer requires a biopsy of the cervix. This is often done through colposcopy, a magnified visual inspection of the cervix aided by using a dilute acetic acid (e.g. vinegar) solution to highlight abnormal cells on the surface of the cervix, with visual contrast provided by staining the normal tissues a mahogany brown with Lugol's iodine.{{cite book | vauthors = Sellors JW |title=Colposcopy and treatment of cervical intraepithelial neoplasia: a beginners' manual |date=2003 |isbn=978-92-832-0412-1 |chapter-url=http://screening.iarc.fr/colpochap.php?lang=1&chap=4 |chapter=Chapter 4: An introduction to colposcopy: indications for colposcopy, instrumentation, principles and documentation of results|publisher=International Agency for Research on Cancer }} Medical devices used for biopsy of the cervix include punch forceps. Colposcopic impression, the estimate of disease severity based on the visual inspection, forms part of the diagnosis. Further diagnostic and treatment procedures are loop electrical excision procedure and cervical conization, in which the inner lining of the cervix is removed to be examined pathologically. These are carried out if the biopsy confirms severe cervical intraepithelial neoplasia.{{cite journal | vauthors = Athanasiou A, Veroniki AA, Efthimiou O, Kalliala I, Naci H, Bowden S, Paraskevaidi M, Arbyn M, Lyons D, Martin-Hirsch P, Bennett P, Paraskevaidis E, Salanti G, Kyrgiou M | display-authors = 6 | title = Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis | journal = The Lancet. Oncology | volume = 23 | issue = 8 | pages = 1097–1108 | date = August 2022 | pmid = 35835138 | pmc = 9630146 | doi = 10.1016/S1470-2045(22)00334-5 }}{{Cite journal |date=2023-11-10 |title=Prevention of cervical cancer: what are the risks and benefits of different treatments? |url=https://evidence.nihr.ac.uk/alert/prevention-of-cervical-cancer-what-are-the-risks-and-benefits-of-different-treatments/ |journal=NIHR Evidence |type=Plain English summary |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_60599|s2cid=265201829 |url-access=subscription }}

File:Squamous carcinoma of the cervix.jpg up higher.]]

Often before the biopsy, the doctor asks for medical imaging to rule out other causes of a woman's symptoms. Imaging modalities such as ultrasound, CT scan, and MRI have been used to look for alternating disease, spread of the tumor, and effect on adjacent structures. Typically, they appear as heterogeneous masses on the cervix.{{cite journal | vauthors = Pannu HK, Corl FM, Fishman EK | title = CT evaluation of cervical cancer: spectrum of disease | journal = Radiographics | volume = 21 | issue = 5 | pages = 1155–1168 | date = September–October 2001 | pmid = 11553823 | doi = 10.1148/radiographics.21.5.g01se311155 }}

Interventions such as playing music during the procedure and viewing the procedure on a monitor can reduce the anxiety associated with the examination.{{cite journal | vauthors = Galaal K, Bryant A, Deane KH, Al-Khaduri M, Lopes AD | title = Interventions for reducing anxiety in women undergoing colposcopy | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 12 | pages = CD006013 | date = December 2011 | pmid = 22161395 | pmc = 4161490 | doi = 10.1002/14651858.cd006013.pub3 }}

IMage:Ca in situ, cervix 2.jpg) of carcinoma in situ (also called CIN3), stage 0: The normal architecture of stratified squamous epithelium is replaced by irregular cells that extend throughout its full thickness. Normal columnar epithelium is also seen.]]

Cervical intraepithelial neoplasia (CIN) means the development of abnormal cells on the surface of the cervix. It is caused by an HPV infection but in most cases, it is resolved by the immune system. However, a small percentage of people might develop a more serious CIN which, if left untreated, can develop into cervical cancer.{{cite book | vauthors = Mello V, Sundstrom RK | chapter = Cervical Intraepithelial Neoplasia |date=2023 | chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK544371/ | title = StatPearls |access-date=2023-11-16 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31335091 }}{{Cite web |title=Cervical Dysplasia: Causes, Symptoms, Diagnosis & Treatment |url=https://my.clevelandclinic.org/health/diseases/15678-cervical-intraepithelial-neoplasia-cin |access-date=2023-11-16 |website=Cleveland Clinic |language=en}} CIN is often diagnosed during routine Pap smear examination or colposcopy.

The naming and histologic classification of cervical carcinoma precursor lesions has changed many times over the 20th century. The World Health Organization classification system was descriptive of the lesions, naming them mild, moderate, or severe dysplasia or carcinoma in situ (CIS).{{cite book |title=Practical principles of cytopathology. Revised edition. |vauthors=DeMay M |publisher=American Society for Clinical Pathology Press |year=2007 |isbn=978-0-89189-549-7 |location=Chicago, IL}} The term cervical intraepithelial neoplasia (CIN) was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardize treatment. For premalignant dysplastic changes, cervical intraepithelial neoplasia grading (CIN 1–3) is used. It classifies mild dysplasia as CIN1, moderate dysplasia as CIN2, and severe dysplasia and CIS as CIN3.{{cite book | vauthors = Salcedo MP, Phoolcharoen N, Schmeler KM | chapter = Intraepithelial neoplasia of the lower genital tract (cervix, vagina, vulva) |date=2022 | title = Comprehensive Gynecology |pages=637–647.e2 |publisher=Elsevier |language=en |doi=10.1016/b978-0-323-65399-2.00038-3 |isbn=978-0-323-65399-2 }} More recently, CIN2 and CIN3 have been combined into CIN2/3. These results are what a pathologist might report from a biopsy.{{citation needed|date=September 2020}}

These should not be confused with the Bethesda system terms for Pap test (cytopathology) results. Among the Bethesda results: Low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). An LSIL Pap may correspond to CIN1, and HSIL may correspond to CIN2 and CIN3, but they are results of different tests, and the Pap test results need not match the histologic findings.{{medical citation needed|date=May 2021}}

Histologic subtypes of invasive cervical carcinoma include:{{cite web |url=http://www.emedicine.com/med/topic324.htm#section~workup |title=Cervical Cancer |access-date=2 December 2007 |vauthors=Garcia A, Hamid O, El-Khoueiry A |date=6 July 2006 |work=eMedicine |publisher=WebMD |url-status=live |archive-url=https://web.archive.org/web/20071209093214/http://www.emedicine.com/med/TOPIC324.HTM#section~workup |archive-date=9 December 2007 }}{{cite news | vauthors = Dolinsky C |title=Cervical Cancer: The Basics |date=17 July 2006 |publisher=Abramson Cancer Center of the University of Pennsylvania | url=http://www.oncolink.upenn.edu/types/article.cfm?c=6&s=17&ss=129&id=8226 | work=OncoLink | access-date=2 December 2007 | archive-url=https://web.archive.org/web/20080118175524/http://www.oncolink.upenn.edu/types/article.cfm?c=6&s=17&ss=129&id=8226 | archive-date=18 January 2008 }}

• Squamous cell carcinoma (about 80–85%{{cite web|title=What Is Cervical Cancer?|url=https://www.cancer.org/cancer/cervical-cancer/about/what-is-cervical-cancer.html|publisher=American Cancer Society}}{{cite web|title=Cervical cancer – Types and grades|url=http://www.cancerresearchuk.org/about-cancer/cervical-cancer/stages-types-grades/types-and-grades|publisher=Cancer Research UK}})
• adenocarcinoma (about 15% of cervical cancers in the UK{{cite web |title = Cancer Research UK website |url = http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/ |access-date = 3 January 2009 |archive-url = https://web.archive.org/web/20090116222837/http://info.cancerresearchuk.org/cancerstats/types/cervix/incidence/ |archive-date = 16 January 2009 }})
• Adenosquamous carcinoma
• Small cell carcinoma
• Neuroendocrine tumour
• Glassy cell carcinoma
• Villoglandular adenocarcinoma

Image:Histopathology of squamous cell carcinoma of the cervix.png|Invasive squamous cell carcinoma of the cervix is characterized by infiltration as irregular anastomosing nests or single cells.{{cite web | vauthors = Turashvili G | title = Squamous cell carcinoma and variants | website= Pathology Outlines |url= https://www.pathologyoutlines.com/topic/cervixscc.html }} This case is poorly differentiated. H&E stain.

File:Immunohistochemistry for p16 in cervical squamous cell carcinoma.jpg|Cervical squamous cell carcinoma generally shows diffuse staining of both nuclei and cytoplasm on p16 immuno-
histochemistry (except verrucous variant).Image by Mikael Häggström, MD. Source for caption: {{cite web|url=https://www.pathologyoutlines.com/topic/cervixscc.html|title=Cervix - Squamous cell carcinoma and variants|website=Pathology Outlines|vauthors=Turashvili G}} Last author update: 24 September 2020

File:Invasive cervical squamous cell carcinoma on H&E histopathology and Ki-67 immunohistochemistry.jpg|Invasive cervical squamous cell carcinoma on H&E histopathology and Ki-67 immunohistochemistry. The latter correlates well with the degree and level of dysplasia.Image by Mikael Häggström, MD. Source for caption: {{cite journal|vauthors=Ghosh A, Nirupama M, Padmanabha N, Kini H| title=Assessment of p16 and Ki67 Immunohistochemistry Expression in Squamous Intraepithelial Lesion with Cytohistomorphological Correlation. | journal=Iran J Pathol | year= 2020 | volume= 15 | issue= 4 | pages= 268–273 | pmid=32944038 | doi=10.30699/ijp.2020.112421.2208 | pmc=7477676 }}

Image:Cervix quadrants and directions.svg|The location of cervical cancer can be described in terms of quadrants, or corresponding to a clock face when the subject is in supine position.

Though squamous cell carcinoma is the cervical cancer with the most incidence, the incidence of adenocarcinoma of the cervix has been increasing in recent decades. Endocervical adenocarcinoma represents 20–25% of the histological types of cervical carcinoma. Gastric-type mucinous adenocarcinoma of the cervix is a rare type of cancer with aggressive behavior. This type of malignancy is not related to high-risk human papillomavirus (HPV).{{cite journal |vauthors = Mulita F, Iliopoulos F, Kehagias I |title = A rare case of gastric-type mucinous endocervical adenocarcinoma in a 59-year-old woman |journal = Przeglad Menopauzalny = Menopause Review |volume = 19 |issue = 3 |pages = 147–150 |date = September 2020 |pmid = 33100952 |pmc = 7573334 |doi = 10.5114/pm.2020.99563 }}

Noncarcinoma malignancies which can rarely occur in the cervix include melanoma and lymphoma. The International Federation of Gynecology and Obstetrics (FIGO) stage does not incorporate lymph node involvement in contrast to the TNM staging for most other cancers. For cases treated surgically, information obtained from the pathologist can be used in assigning a separate pathologic stage but is not to replace the original clinical stage.{{citation needed|date=September 2020}}

{{Main|Cervical cancer staging}}

Cervical cancer is staged by the FIGO system, which is based on clinical examination rather than surgical findings. Before the 2018 revisions to FIGO staging, the system allowed only these diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervical conization. However, the system allows use of any imaging or pathological methods for staging.{{cite journal |vauthors = Bhatla N, Berek JS, Cuello Fredes M, Denny LA, Grenman S, Karunaratne K, Kehoe ST, Konishi I, Olawaiye AB, Prat J, Sankaranarayanan R, Brierley J, Mutch D, Querleu D, Cibula D, Quinn M, Botha H, Sigurd L, Rice L, Ryu HS, Ngan H, Mäenpää J, Andrijono A, Purwoto G, Maheshwari A, Bafna UD, Plante M, Natarajan J |display-authors = 6 |title = Revised FIGO staging for carcinoma of the cervix uteri |journal = International Journal of Gynaecology and Obstetrics |volume = 145 |issue = 1 |pages = 129–135 |date = April 2019 |pmid = 30656645 |doi = 10.1002/ijgo.12749 |s2cid = 58656013 }}

File:Diagram showing stage 1A cervical cancer CRUK 200.svg|Stage 1A cervical cancer

File:Diagram showing stage 1B cervical cancer CRUK 203.svg|Stage 1B cervical cancer

File:Diagram showing stage 2A cervical cancer CRUK 212.svg|Stage 2A cervical cancer

File:Diagram showing stage 2B cervical cancer CRUK 216.svg|Stage 2B cervical cancer

File:Diagram showing stage 3B cervical cancer CRUK 226.svg|Stage 3B cervical cancer

File:Diagram showing stage 4A cervical cancer CRUK 236.svg|Stage 4A cervical cancer

File:Diagram showing stage 4B cervical cancer CRUK 239.svg|Stage 4B cervical cancer

==Prevention {{Anchor | prevention}}==

File:Cervical screening Test Vehicle in Minsheng Community 20120421.jpg]]

File:VIANeg.gif

File:VIAPosCIN1.gif]]

{{Main|Cervical screening|Pap test}}

Checking cervical cells with the Papanicolaou test (Pap test) for cervical pre-cancer has dramatically reduced the number of cases of, and mortality from, cervical cancer. Liquid-based cytology may reduce the number of inadequate samples.{{cite journal |vauthors=Payne N, Chilcott J, McGoogan E |title=Liquid-based cytology in cervical screening: a rapid and systematic review |journal=Health Technology Assessment |volume=4 |issue=18 |pages=1–73 |year=2000 |pmid=10932023 |doi=10.3310/hta4180 |doi-access=free}}{{cite journal |vauthors=Karnon J, Peters J, Platt J, Chilcott J, McGoogan E, Brewer N |title=Liquid-based cytology in cervical screening: an updated rapid and systematic review and economic analysis |journal=Health Technology Assessment |volume=8 |issue=20 |pages=iii, 1-iii, 78 |date=May 2004 |pmid=15147611 |doi=10.3310/hta8200 |doi-access=free}}{{cite web |url=http://www.cancerscreening.nhs.uk/cervical/lbc.html |title=Liquid Based Cytology (LBC): NHS Cervical Screening Programme|archive-url=https://web.archive.org/web/20110108144400/http://www.cancerscreening.nhs.uk/cervical/lbc.html |archive-date=8 January 2011 |url-status=live |access-date=1 October 2010}} Pap test screening every three to five years with appropriate follow-up can reduce cervical cancer incidence up to 80%.{{cite journal | vauthors = Arbyn M, Anttila A, Jordan J, Ronco G, Schenck U, Segnan N, Wiener H, Herbert A, von Karsa L | display-authors = 6 | title = European Guidelines for Quality Assurance in Cervical Cancer Screening. Second edition--summary document | journal = Annals of Oncology | volume = 21 | issue = 3 | pages = 448–458 | date = March 2010 | pmid = 20176693 | pmc = 2826099 | doi = 10.1093/annonc/mdp471 }}

Pap test screening can reveal abnormal cells on the surface of the cervix called cervical intraepithelial neoplasia (CIN) which in a small percentage can develop into cervical cancer. These precancerous changes can be confirmed with further examination known as colposcopy.

Personal invitations encouraging women to get screened are effective at increasing the likelihood they will do so. Educational materials also help increase the likelihood that women will go for screening, but they are not as effective as invitations.{{cite journal | vauthors = Staley H, Shiraz A, Shreeve N, Bryant A, Martin-Hirsch PP, Gajjar K | title = Interventions targeted at women to encourage the uptake of cervical screening | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 9 | pages = CD002834 | date = September 2021 | pmid = 34694000 | pmc = 8543674 | doi = 10.1002/14651858.CD002834.pub3 }}

According to the 2010 European guidelines, the age at which to start screening ranges between 20 and 30 years of age, but preferentially not before age 25 or 30 years, and depends on the burden of the disease in the population and the available resources.

In the United States, screening is recommended to begin at age 21, regardless of the age at which a woman began having sex or other risk factors. Pap tests should be done every three years between the ages of 21 and 65. In women over the age of 65, screening may be discontinued if no abnormal screening results were seen within the previous 10 years and no history of CIN2 or higher exists.{{cite web|title=Cervical Cancer Screening Guidelines for Average-Risk Women|website=cdc.gov |url=https://www.cdc.gov/cancer/cervical/pdf/guidelines.pdf |access-date=8 November 2014|url-status=live|archive-url=https://web.archive.org/web/20150201182536/http://www.cdc.gov/cancer/cervical/pdf/guidelines.pdf|archive-date=1 February 2015}}{{cite journal |vauthors=Karjane N, Chelmow D |title=New cervical cancer screening guidelines, again |journal=Obstetrics and Gynecology Clinics of North America |volume=40 |issue=2 |pages=211–223 |date=June 2013 |pmid=23732026 |doi=10.1016/j.ogc.2013.03.001}} HPV vaccination status does not change screening rates.{{cite journal |title=ACOG Practice Bulletin Number 131: Screening for cervical cancer |journal=Obstetrics and Gynecology |volume=120 |issue=5 |pages=1222–1238 |date=November 2012 |pmid=23090560 |doi=10.1097/AOG.0b013e318277c92a |author1=Committee on Practice Bulletins—Gynecology}}

A number of recommended options exist for screening those 30 to 65. This includes cervical cytology every 3 years, HPV testing every 5 years, or HPV testing together with cytology every 5 years.{{cite journal | vauthors = Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW, Kemper AR, Kubik M, Landefeld CS, Mangione CM, Phipps MG, Silverstein M, Simon MA, Tseng CW, Wong JB | display-authors = 6 | title = Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement | journal = JAMA | volume = 320 | issue = 7 | pages = 674–686 | date = August 2018 | pmid = 30140884 | doi = 10.1001/jama.2018.10897 | doi-access = free }} Screening is not beneficial before age 25, as the rate of disease is low. Screening is not beneficial in women older than 60 years if they have a history of negative results. The American Society of Clinical Oncology guideline has recommend for different levels of resource availability.{{cite journal | vauthors = Arrossi S, Temin S, Garland S, Eckert LO, Bhatla N, Castellsagué X, Alkaff SE, Felder T, Hammouda D, Konno R, Lopes G, Mugisha E, Murillo R, Scarinci IC, Stanley M, Tsu V, Wheeler CM, Adewole IF, de Sanjosé S | display-authors = 6 | title = Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline | journal = Journal of Global Oncology | volume = 3 | issue = 5 | pages = 611–634 | date = October 2017 | pmid = 29094100 | pmc = 5646902 | doi = 10.1200/JGO.2016.008151 }}

Pap tests have not been as effective in developing countries.{{Cite book|title = Comprehensive cervical cancer control. A guide to essential practice | edition = Second | publisher = World Health Organization|year = 2014|isbn = 978-92-4-154895-3|url =https://www.who.int/reproductivehealth/publications/cancers/cervical-cancer-guide/en/|url-status = live|archive-url = https://web.archive.org/web/20150504101022/http://www.who.int/reproductivehealth/publications/cancers/cervical-cancer-guide/en/|archive-date = 4 May 2015}} This is in part because many of these countries have an impoverished health care infrastructure, too few trained and skilled professionals to obtain and interpret Pap tests, uninformed women who get lost to follow-up, and a lengthy turn-around time to get results. Visual inspection with acetic acid and HPV DNA testing has been tried, though with mixed success.

{{Main|HPV vaccine}}

There are six licensed HPV vaccines: three bivalent (protect against two types of HPV), two quadrivalent (against four), and one nonavalent vaccine (against nine) Three HPV vaccines (Gardasil, Gardasil 9, and Cervarix) reduce the risk of cancerous or precancerous changes of the cervix and perineum by about 93% and 62%, respectively.{{cite journal | vauthors = Medeiros LR, Rosa DD, da Rosa MI, Bozzetti MC, Zanini RR | title = Efficacy of human papillomavirus vaccines: a systematic quantitative review | journal = International Journal of Gynecological Cancer | volume = 19 | issue = 7 | pages = 1166–1176 | date = October 2009 | pmid = 19823051 | doi = 10.1111/IGC.0b013e3181a3d100 | s2cid = 24695684 | doi-access = free }} All have excellent safety profiles and are highly efficacious, or have met immunobridging standards.{{rp|p=668}} The vaccines are between 92% and 100% effective against HPV 16 and 18 up to at least 8 years.

HPV vaccines are typically given to ages 9 to 26, as the vaccine is most effective if given before infection occurs. The primary target group in most of the countries recommending HPV vaccination is young adolescent girls, aged 9-14. As of 2022, 125 countries include HPV vaccines in their routine vaccinations for girls, and 47 countries recommend them for boys, as well,{{rp|p=654}} including Japan.{{Cite journal|title=Risk-Benefit Analysis of the 9-Valent HPV Vaccination for Adolescent Boys from an Individual Perspective|first=Taito|last=Kitano|date=24 March 2022|journal=Japanese Journal of Infectious Diseases|volume=75|issue=2|pages=114–120|doi=10.7883/yoken.JJID.2021.367|pmid=34334535|doi-access=free}}

The duration of effectiveness and whether a booster will be needed is unknown. The high cost of this vaccine has been a cause for concern. Several countries have considered (or are considering) programs to fund HPV vaccination. The American Society of Clinical Oncology guideline has recommendations for different levels of resource availability.

{{Main|Safe sex}}

Barrier protection or spermicidal gel use during sexual intercourse decreases but does not eliminate the risk of transmitting the infection. Condoms may protect against genital warts.{{cite journal | vauthors = Manhart LE, Koutsky LA | title = Do condoms prevent genital HPV infection, external genital warts, or cervical neoplasia? A meta-analysis | journal = Sexually Transmitted Diseases | volume = 29 | issue = 11 | pages = 725–735 | date = November 2002 | pmid = 12438912 | doi = 10.1097/00007435-200211000-00018 | s2cid = 9869956 | doi-access = free }} They also protect against other sexually transmitted infections, such as HIV and Chlamydia, which are associated with greater risks of developing cervical cancer.{{medical citation needed|date=May 2021}}

Vitamin A is associated with a lower risk{{cite journal | vauthors = Zhang X, Dai B, Zhang B, Wang Z | title = Vitamin A and risk of cervical cancer: a meta-analysis | journal = Gynecologic Oncology | volume = 124 | issue = 2 | pages = 366–373 | date = February 2012 | pmid = 22005522 | doi = 10.1016/j.ygyno.2011.10.012 }} as are vitamin B12, vitamin C, vitamin E, and beta-Carotene.{{cite journal | vauthors = Myung SK, Ju W, Kim SC, Kim H | title = Vitamin or antioxidant intake (or serum level) and risk of cervical neoplasm: a meta-analysis | journal = BJOG | volume = 118 | issue = 11 | pages = 1285–1291 | date = October 2011 | pmid = 21749626 | doi = 10.1111/j.1471-0528.2011.03032.x | hdl-access = free | s2cid = 38761694 | hdl = 2027.42/86903 }}

File:Cervical Cryotherapy.png

The treatment of cervical cancer varies worldwide, largely due to access to surgeons skilled in radical pelvic surgery and the emergence of fertility-sparing therapy in developed nations. Less advanced stages of cervical cancer typically have treatment options that allow fertility to be maintained if the patient desires.{{Cite web|title=Cervical Cancer Treatment Options {{!}} Treatment Choices by Stage|url=https://www.cancer.org/cancer/cervical-cancer/treating/by-stage.html|access-date=12 September 2020|website=www.cancer.org}}

Because cervical cancers are radiosensitive, radiation may be used in all stages where surgical options do not exist. Surgical intervention may have better outcomes than radiological approaches.{{cite journal | vauthors = Baalbergen A, Veenstra Y, Stalpers L | title = Primary surgery versus primary radiotherapy with or without chemotherapy for early adenocarcinoma of the uterine cervix | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 1 | pages = CD006248 | date = January 2013 | pmid = 23440805 | pmc = 7387233 | doi = 10.1002/14651858.CD006248.pub3 }} In addition, chemotherapy can be used to treat cervical cancer and is more effective than radiation alone.{{cite journal | vauthors = Einhorn N, Tropé C, Ridderheim M, Boman K, Sorbe B, Cavallin-Ståhl E | title = A systematic overview of radiation therapy effects in cervical cancer (cervix uteri) | journal = Acta Oncologica | volume = 42 | issue = 5–6 | pages = 546–556 | date = 2003 | pmid = 14596512 | doi = 10.1080/02841860310014660 | doi-access = free }} Chemoradiotherapy may increase overall survival and reduce the risk of disease recurrence compared to radiotherapy alone.{{cite journal | title = Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: individual patient data meta-analysis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD008285 | date = January 2010 | pmid = 20091664 | pmc = 7105912 | doi = 10.1002/14651858.cd008285 | author1 = Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration (CCCMAC) | volume = 2010 }}

Precancerous cells (cervical intraepithelial neoplasia) that would lead to cancer and early-stage cervical cancer (IA1) can be treated effectively by various surgical techniques. Surgical treatment methods include excision, where a cone-shaped portion of the cervix is removed, and ablation which removes only the parts with abnormal tissues. While these effectively reduce the risk of cancer developing or spreading, they cause an increased risk of premature birth in future pregnancies. Surgical techniques that remove more cervical tissue come with less risk of the cancer recurring but a higher chance of giving birth prematurely. Due to this risk, taking into account the age, childbearing plans of the woman, and the size and location of the cancer cells are crucial for choosing the right procedure. There is low-certainty evidence that peri-operative care approaches, such as 'fast-track surgery' or 'enhanced recovery programmes' may lower surgical stress and improve recovery after gynaecological cancer surgery.{{cite journal |vauthors=Chau JP, Liu X, Lo SH, Chien WT, Hui SK, Choi KC, Zhao J |date=March 2022 |title=Perioperative enhanced recovery programmes for women with gynaecological cancers |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue=3 |pages=CD008239 |doi=10.1002/14651858.CD008239.pub5 |pmc=8922407 |pmid=35289396}}

Microinvasive cancer (stage IA) may also be treated by hysterectomy (removal of the whole uterus, including part of the vagina).{{cite journal | vauthors = van Nagell JR, Greenwell N, Powell DF, Donaldson ES, Hanson MB, Gay EC | title = Microinvasive carcinoma of the cervix | journal = American Journal of Obstetrics and Gynecology | volume = 145 | issue = 8 | pages = 981–991 | date = April 1983 | pmid = 6837683 | doi = 10.1016/0002-9378(83)90852-9 }} For stage IA2, the lymph nodes are removed as well. Alternatives include local surgical procedures such as a loop electrical excision procedure or cone biopsy.{{cite web | vauthors = Erstad S | title=Cone biopsy (conization) for abnormal cervical cell changes | date=12 January 2007 | website=WebMD | url=http://www.webmd.com/cancer/cervical-cancer/cone-biopsy-conization-for-abnormal-cervical-cell-changes | access-date=2 December 2007 | url-status=live | archive-url=https://web.archive.org/web/20071119114319/http://www.webmd.com/cancer/cervical-cancer/cone-biopsy-conization-for-abnormal-cervical-cell-changes | archive-date=19 November 2007 }}{{cite journal | vauthors = Lin Y, Zhou J, Dai L, Cheng Y, Wang J | title = Vaginectomy and vaginoplasty for isolated vaginal recurrence 8 years after cervical cancer radical hysterectomy: A case report and literature review | journal = The Journal of Obstetrics and Gynaecology Research | volume = 43 | issue = 9 | pages = 1493–1497 | date = September 2017 | pmid = 28691384 | doi = 10.1111/jog.13375 | s2cid = 42161609 }} A systematic review concluded that more evidence is needed to inform decisions about different surgical techniques for women with cervical cancer at stage IA2.{{cite journal | vauthors = Kokka F, Bryant A, Brockbank E, Jeyarajah A | title = Surgical treatment of stage IA2 cervical cancer | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD010870 | date = May 2014 | volume = 2018 | pmid = 24874726 | pmc = 6513277 | doi = 10.1002/14651858.cd010870.pub2 }}

If a cone biopsy does not produce clear margins{{cite journal | vauthors = Jones WB, Mercer GO, Lewis JL, Rubin SC, Hoskins WJ | title = Early invasive carcinoma of the cervix | journal = Gynecologic Oncology | volume = 51 | issue = 1 | pages = 26–32 | date = October 1993 | pmid = 8244170 | doi = 10.1006/gyno.1993.1241 }} (findings on biopsy showing that the tumor is surrounded by cancer free tissue, suggesting all of the tumor is removed), one more possible treatment option for women who want to preserve their fertility is a trachelectomy.{{cite web |url=http://www.baymoon.com/~gyncancer/library/glossary/bldeftrachelect.htm |title=Trachelectomy |access-date=2 December 2007 | vauthors = Dolson L |year=2001 |archive-url=https://web.archive.org/web/20070927143641/http://www.baymoon.com/~gyncancer/library/glossary/bldeftrachelect.htm |archive-date=27 September 2007 }} This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care,{{cite journal | vauthors = Burnett AF | title = Radical trachelectomy with laparoscopic lymphadenectomy: review of oncologic and obstetrical outcomes | journal = Current Opinion in Obstetrics & Gynecology | volume = 18 | issue = 1 | pages = 8–13 | date = February 2006 | pmid = 16493253 | doi = 10.1097/01.gco.0000192968.75190.dc | s2cid = 22958941 }} as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the woman is under general anaesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the woman consented. Due to the possible risk of cancer spreading to the lymph nodes in stage 1B cancers and some stage 1A cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation.{{citation needed|date=September 2017}}

A radical trachelectomy can be performed abdominally{{cite journal | vauthors = Cibula D, Ungár L, Svárovský J, Zivný J, Freitag P | title = [Abdominal radical trachelectomy--technique and experience] | language = cs | journal = Ceska Gynekologie | volume = 70 | issue = 2 | pages = 117–122 | date = March 2005 | pmid = 15918265 }} or vaginally{{cite journal | vauthors = Plante M, Renaud MC, Hoskins IA, Roy M | title = Vaginal radical trachelectomy: a valuable fertility-preserving option in the management of early-stage cervical cancer. A series of 50 pregnancies and review of the literature | journal = Gynecologic Oncology | volume = 98 | issue = 1 | pages = 3–10 | date = July 2005 | pmid = 15936061 | doi = 10.1016/j.ygyno.2005.04.014 }} and opinions are conflicting as to which is better.{{cite journal | vauthors = Roy M, Plante M, Renaud MC, Têtu B | title = Vaginal radical hysterectomy versus abdominal radical hysterectomy in the treatment of early-stage cervical cancer | journal = Gynecologic Oncology | volume = 62 | issue = 3 | pages = 336–339 | date = September 1996 | pmid = 8812529 | doi = 10.1006/gyno.1996.0245 }} A radical abdominal trachelectomy with lymphadenectomy usually only requires a two- to three-day hospital stay, and most women recover very quickly (about six weeks). Complications are uncommon, although women who can conceive after surgery are susceptible to preterm labour and possible late miscarriage.{{cite journal | vauthors = Dargent D, Martin X, Sacchetoni A, Mathevet P | title = Laparoscopic vaginal radical trachelectomy: a treatment to preserve the fertility of cervical carcinoma patients | journal = Cancer | volume = 88 | issue = 8 | pages = 1877–1882 | date = April 2000 | pmid = 10760765 | doi = 10.1002/(SICI)1097-0142(20000415)88:8<1877::AID-CNCR17>3.0.CO;2-W | doi-access = free }} A wait of at least one year is generally recommended before attempting to become pregnant after surgery.{{cite journal | vauthors = Schlaerth JB, Spirtos NM, Schlaerth AC | title = Radical trachelectomy and pelvic lymphadenectomy with uterine preservation in the treatment of cervical cancer | journal = American Journal of Obstetrics and Gynecology | volume = 188 | issue = 1 | pages = 29–34 | date = January 2003 | pmid = 12548192 | doi = 10.1067/mob.2003.124 }} Recurrence in the residual cervix is rare if the trachelectomy has cleared the cancer. Yet, women are recommended to practice vigilant prevention and follow-up care, including Pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 3–4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive.{{citation needed|date=September 2017}}

Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Women treated with surgery who have high-risk features found on pathologic examination are given radiation therapy with or without chemotherapy to reduce the risk of relapse.{{citation needed|date=September 2017}} A Cochrane review has found moderate-certainty evidence that radiation decreases the risk of disease progression in people with stage IB cervical cancer when compared to no further treatment.{{cite journal | vauthors = Rogers L, Siu SS, Luesley D, Bryant A, Dickinson HO | title = Radiotherapy and chemoradiation after surgery for early cervical cancer | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD007583 | date = May 2012 | volume = 5 | pmid = 22592722 | pmc = 4171000 | doi = 10.1002/14651858.cd007583.pub3 }} However, little evidence was found on its effects on overall survival.

File:Diagram showing the position of the applicators for internal radiotherapy for cervical cancer CRUK 344.svg

Larger early-stage tumors (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy. When cisplatin is present, it is thought to be the most active single agent in periodic diseases.{{cite journal | vauthors = Waggoner SE | title = Cervical cancer | journal = Lancet | volume = 361 | issue = 9376 | pages = 2217–2225 | date = June 2003 | pmid = 12842378 | doi = 10.1016/S0140-6736(03)13778-6 | s2cid = 24115541 }} Such addition of platinum-based chemotherapy to chemoradiation seems not only to improve survival but also reduces risk of recurrence in women with early-stage cervical cancer (IA2–IIA).{{cite journal | vauthors = Falcetta FS, Medeiros LR, Edelweiss MI, Pohlmann PR, Stein AT, Rosa DD | title = Adjuvant platinum-based chemotherapy for early stage cervical cancer | journal = The Cochrane Database of Systematic Reviews | volume = 11 | pages = CD005342 | date = November 2016 | issue = 11 | pmid = 27873308 | pmc = 4164460 | doi = 10.1002/14651858.CD005342.pub4 }} A Cochrane review found a lack of evidence on the benefits and harms of primary hysterectomy compared to primary chemoradiotherapy for cervical cancer in stage IB2.{{cite journal | vauthors = Nama V, Angelopoulos G, Twigg J, Murdoch JB, Bailey J, Lawrie TA | title = Type II or type III radical hysterectomy compared to chemoradiotherapy as a primary intervention for stage IB2 cervical cancer | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 10 | pages = CD011478 | date = October 2018 | pmid = 30311942 | pmc = 6516889 | doi = 10.1002/14651858.cd011478.pub2 }}

Advanced-stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. On 15 June 2006, the US Food and Drug Administration approved the use of a combination of two chemotherapy drugs, hycamtin and cisplatin, for women with late-stage (IVB) cervical cancer treatment.{{cite news | title=FDA Approves First Drug Treatment for Late-Stage Cervical Cancer | date=15 June 2006 | publisher=U.S. Food and Drug Administration | url=https://www.fda.gov/bbs/topics/NEWS/2006/NEW01391.html | access-date=2 December 2007 | url-status=dead | archive-url=https://web.archive.org/web/20071010035641/https://www.fda.gov/bbs/topics/NEWS/2006/NEW01391.html | archive-date=10 October 2007 }} Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects.{{cite journal | vauthors = Moon JY, Song IC, Ko YB, Lee HJ | title = The combination of cisplatin and topotecan as a second-line treatment for patients with advanced/recurrent uterine cervix cancer | journal = Medicine | volume = 97 | issue = 14 | pages = e0340 | date = April 2018 | pmid = 29620661 | pmc = 5902288 | doi = 10.1097/MD.0000000000010340 }}

There is insufficient evidence of whether anticancer drugs after standard care help women with locally advanced cervical cancer to live longer.{{cite journal | vauthors = Tangjitgamol S, Katanyoo K, Laopaiboon M, Lumbiganon P, Manusirivithaya S, Supawattanabodee B | title = Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD010401 | date = December 2014 | volume = 2019 | pmid = 25470408 | pmc = 6402532 | doi = 10.1002/14651858.cd010401.pub2 }}

For surgery to be curative, the entire cancer must be removed with no cancer found at the margins of the removed tissue on examination under a microscope. This procedure is known as exenteration.{{cite journal | vauthors = Sardain H, Lavoue V, Redpath M, Bertheuil N, Foucher F, Levêque J | title = Curative pelvic exenteration for recurrent cervical carcinoma in the era of concurrent chemotherapy and radiation therapy. A systematic review | journal = European Journal of Surgical Oncology | volume = 41 | issue = 8 | pages = 975–985 | date = August 2015 | pmid = 25922209 | doi = 10.1016/j.ejso.2015.03.235 | s2cid = 21911045 | url = https://hal-univ-rennes1.archives-ouvertes.fr/hal-01147372/file/Curative%20Pelvic%20Exenteration%20For%20Recurrent%20Cervical.pdf }}

No evidence is available to suggest that any form of follow-up approach is better or worse in terms of prolonging survival, improving quality of life, or guiding the management of problems that can arise because of the treatment and that in the case of radiotherapy treatment worsen with time.{{cite journal | vauthors = Lanceley A, Fiander A, McCormack M, Bryant A | title = Follow-up protocols for women with cervical cancer after primary treatment | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD008767 | date = November 2013 | volume = 2014 | pmid = 24277645 | doi = 10.1002/14651858.CD008767.pub2 | pmc = 8969617 | collaboration = Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Group }} A 2019 review found no controlled trials regarding the efficacy and safety of interventions for vaginal bleeding in women with advanced cervical cancer.{{cite journal | vauthors = Eleje GU, Eke AC, Igberase GO, Igwegbe AO, Eleje LI | title = Palliative interventions for controlling vaginal bleeding in advanced cervical cancer | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 3 | pages = CD011000 | date = March 2019 | pmid = 30888060 | pmc = 6423555 | doi = 10.1002/14651858.cd011000.pub3 }}

Immunotherapy with immune checkpoint inhibitors, such as pembrolizumab (Keytruda), has also been approved by the U.S. Food and Drug Administration (FDA) for certain patients with recurrent or metastatic cervical cancer, demonstrating promising results in ongoing clinical trials. {{cite web |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-cervical-cancer |title=FDA Approves Pembrolizumab for Advanced Cervical Cancer |publisher=U.S. Food and Drug Administration |date=12 June 2018 |access-date=12 January 2025 |archive-url=https://web.archive.org/web/20220110000000/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-advanced-cervical-cancer |archive-date=10 January 2022}}{{cite journal |vauthors=Colomban L, Le Tourneau C |title=Immunotherapy in Cervical Cancer: Advances and Perspectives |journal=Cancers (Basel) |volume=14 |issue=15 |pages=3803 |date=July 2022 |pmid=35955074 |doi=10.3390/cancers14153803 |doi-access=free |pmc=9330146}} In October 2021, the FDA expanded this approval to include pembrolizumab in combination with chemotherapy, with or without bevacizumab, for people with persistent, recurrent, or metastatic cervical cancer, underscoring the potential of immunotherapeutic approaches in this setting. {{cite web |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-cervical-cancer-new-dosing-regimen |title=FDA Approves Pembrolizumab for Cervical Cancer with a New Dosing Regimen |publisher=U.S. Food and Drug Administration |date=13 October 2021 |access-date=12 January 2025 |archive-url=https://web.archive.org/web/20220110000000/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-cervical-cancer-new-dosing-regimen |archive-date=10 January 2022}} Additional immunotherapy agents, including other PD-1 and PD-L1 inhibitors, are under investigation and have similarly shown encouraging outcomes in clinical studies.

Another immune checkpoint inhibitor, cemiplimab-rwlc (Libtayo), received FDA approval in September 2022 for patients with recurrent or metastatic cervical cancer that has progressed on or after chemotherapy, further highlighting the expanding role of immunotherapeutic strategies in advanced disease. {{cite web |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-recurrent-or-metastatic-cervical-cancer-disease-progression-or-after-chemotherapy |title=FDA Approves Cemiplimab-rwlc for Recurrent or Metastatic Cervical Cancer with Disease Progression on or after Chemotherapy |publisher=U.S. Food and Drug Administration |date=29 September 2022 |access-date=12 January 2025 |archive-url=https://web.archive.org/web/20230101000000/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-recurrent-or-metastatic-cervical-cancer-disease-progression-or-after-chemotherapy |archive-date=1 January 2023}}

Tisotumab vedotin (Tivdak) was approved for medical use in the United States in September 2021.{{Cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761208s000lbl.pdf|title=Enforcement Reports|access-date=21 September 2021|archive-date=21 September 2021|archive-url=https://web.archive.org/web/20210921051657/https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761208s000lbl.pdf}}{{cite web | title=Seagen and Genmab Announce FDA Accelerated Approval for Tivdak (tisotumab vedotin-tftv) in Previously Treated Recurrent or Metastatic Cervical Cancer | publisher=Seagen | via=Business Wire | date=20 September 2021 | url=https://www.businesswire.com/news/home/20210920005921/en/ | access-date=20 September 2021}}

File:Diagram showing the area removed with a posterior exenteration for cancer of the cervix CRUK 288.svg|Diagram showing the area removed with a posterior surgery

File:Diagram showing the area removed with a total exenteration operation for cancer of the cervix CRUK 289.svg|Diagram showing the area removed with a total operation

File:Diagram showing the area removed with an anterior exenteration operation for cancer of the cervix CRUK 290.svg|Diagram showing the area removed with an anterior operation

The prognosis depends on the stage of the cancer. The prognosis for squamous cell carcinoma and adenocarcinoma of the cervix is the same for each given stage. For intraepithelial cervical neoplasms, the prognosis is good.{{cite book | vauthors = Mello V, Sundstrom RK | chapter = Cervical Intraepithelial Neoplasia. | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing | date = January 2022 | pmid = 31335091 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK544371/ }} With treatment, the five-year survival rate for FIGO stage 1 (cancer confined to the cervix) cervical cancer is 85%, and the overall (all stages combined) five-year survival rate is about 66%.{{cite web|url=https://www.cancer.org/cancer/cervical-cancer/detection-diagnosis-staging/survival.html|title=Survival Rates for Cervical Cancer |access-date=27 February 2022 |date=January 3, 2020|publisher=American Cancer Society |archive-url = https://web.archive.org/web/20220227182815/https://www.cancer.org/cancer/cervical-cancer/detection-diagnosis-staging/survival.html|archive-date = 27 February 2022}} Five-year survival in Stage 2 disease (cancer invading beyond upper two-thirds of uterus) is 65%. Stage 3 disease (in which the lower one-third of vagina, pelvic wall is involved or presence of hydronephrosis, pelvic or peri-aortic lymph node involvement) is 35%. Stage 4 disease, in which cancer extends beyond the pelvis, or involves the bladder or rectum, has a 5 year survival rate of 7%.

About 35% of women with invasive cervical cancer have persistent or recurrent disease after treatment.{{cite web | title=Cervical Cancer | work=Cervical Cancer: Pathology, Symptoms and Signs, Diagnosis, Prognosis and Treatment | url=http://www.health.am/cr/cervical-cancer/ | publisher=Armenian Health Network, Health.am | url-status=live | archive-url=https://web.archive.org/web/20070207232901/http://www.health.am/cr/cervical-cancer/ | archive-date=7 February 2007 }}

There is an ethnic disparity in five-year survival in the United States. Average survival rates of the dominant squamous cell carcinoma are 72% for Hispanic and Asian-Pacific women, 68% for White women and 61% for Black women.{{cite journal |last1=Cohen |first1=Camryn M. |last2=Wentzensen |first2=Nicolas |last3=Castle |first3=Philip E. |last4=Schiffman |first4=Mark |last5=Zuna |first5=Rosemary |last6=Arend |first6=Rebecca C. |last7=Clarke |first7=Megan A. |title=Racial and Ethnic Disparities in Cervical Cancer Incidence, Survival, and Mortality by Histologic Subtype |journal=Journal of Clinical Oncology |date=December 1, 2022 |volume=41 |issue=5 |pages=1059–1068 |doi=10.1200/JCO.22.01424 |publisher=ASCO Publications|pmid=36455190 |pmc=9928618 }}

Regular screening has meant that precancerous changes and early-stage cervical cancers have been detected and treated early. Figures suggest that cervical screening is saving 5,000 lives each year in the UK by preventing cervical cancer.{{cite web | title=Cervical cancer statistics and prognosis | url=http://www.cancerhelp.org.uk/help/default.asp?page=9260 | publisher=Cancer Research UK | access-date=24 March 2007 | archive-url=https://web.archive.org/web/20070520092010/http://www.cancerhelp.org.uk/help/default.asp?page=9260 | archive-date=20 May 2007 }}

About 1,000 women per year die of cervical cancer in the UK. All of the Nordic countries have cervical cancer screening programs in place.{{cite journal | vauthors = Nygård M | title = Screening for cervical cancer: when theory meets reality | journal = BMC Cancer | volume = 11 | page = 240 | date = June 2011 | pmid = 21668947 | pmc = 3146446 | doi = 10.1186/1471-2407-11-240 | doi-access = free }} The Pap test was integrated into clinical practice in the Nordic countries in the 1960s.

In Africa, outcomes are often worse as diagnosis is frequently at a later stage of the disease.{{cite journal | vauthors = Muliira RS, Salas AS, O'Brien B | title = Quality of Life among Female Cancer Survivors in Africa: An Integrative Literature Review | journal = Asia-Pacific Journal of Oncology Nursing | volume = 4 | issue = 1 | pages = 6–17 | date = 2016 | pmid = 28217724 | pmc = 5297234 | doi = 10.4103/2347-5625.199078 | doi-access = free }} In a scoping review of publicly-available cervical cancer prevention and control plans from African countries, plans tended to emphasize survivorship rather than early HPV diagnosis and prevention.{{Cite journal| vauthors = Dutta T, Meyerson B, Agley J |date=2018|title=African cervical cancer prevention and control plans: A scoping review|journal=Journal of Cancer Policy|volume=16|pages=73–81|doi=10.1016/j.jcpo.2018.05.002|s2cid=81552501}}

Chemotherapy works by attacking cells that rapidly divide. This kills cancer cells, but can also impact normal cells leading to adverse side effects. Common chemotherapy side effects include; hair loss, mouth sores, loss of appetite, diarrhea, nausea and vomiting, premature menopause, infertility, and damage to the blood-forming cells within bone marrow. Most acute side effects are temporary, dissipating when treatment ceases, but some can be long-lasting or permanent. Long-term chemotherapy side effects include changes in the menstrual cycle, neuropathy, and nephrotoxicity.{{cite web |title=Chemotherapy for Cervical Cancer |url=https://www.cancer.org/cancer/types/cervical-cancer/treating/chemotherapy.html |website=www.cancer.org |publisher=American Cancer Society |access-date=24 October 2024 |date=June 28, 2024}}

Radiation therapy (RT) adverse effects; for a complete side effect list see {{Main|Radiation therapy#Side effects}}

Curative cervical radiation therapy may affect unintended tissues located within the delivery pathway(s) or adjacent to the target lesion, each tissue with a unique sensitivity and response to radiation injury. Common acute RT effects involve the gastrointestinal system, e.g., diarrhea and constipation; urinary tract, e.g., frequent urination; and may cause cervicitis. Common late RT complications include: infertility or premature ovarian failure; vaginal stenosis; lower motor neuron syndrome; telangiectasias, and subsequent hemorrhage; and progressive myelopathy, which may result in irreversible neurologic deficits ranging from minor sensory symptoms to complete paraplegia.{{cite book |last1=Majeed |first1=Hafsa |last2=Gupta |first2=Vikas |title=Adverse Effects of Radiation Therapy |date=August 14, 2023 |publisher=StatPearls Publishing LLC. |url=https://www.ncbi.nlm.nih.gov/books/NBK563259/ |pmid=33085406 |id=NBK563259 |access-date=24 October 2024}} Radiotherapy late effects (with occurrence rates) include osteonecrosis (8-20%), bladder ulceration (<3%), vaginal stenosis (>2.5%){{cite journal |last1=Schmitt |first1=Luiza G. |last2=Amarnath |first2=Sudha R. |title=Late Effects of Pelvic Radiation Therapy in the Female Patient: A Comprehensive Review |journal=Applied Radiation Oncology |date=September 1, 2023 |volume=2023 |issue=3 |pages=13–24 |doi=10.37549/ARO-D-23-00016 |url=https://www.appliedradiationoncology.com/articles/late-effects-of-pelvic-radiation-therapy-in-the-female-patient-a-comprehensive-review |access-date=16 October 2024|url-access=subscription }} and chronic pelvic radiation disease (1-10%), e.g., irreversible lumbosacral plexopathy.{{cite journal |last1=Huh |first1=Jung Wook |last2=Tanksley |first2=Jarred |last3=Chino |first3=Junzo |last4=Willett |first4=Christopher G. |last5=Dewhirst |first5=Mark W. |title=Long-term Consequences of Pelvic Irradiation: Toxicities, Challenges, and Therapeutic Opportunities with Pharmacologic Mitigators |journal=Clinical Cancer Research |date=July 1, 2020 |volume=26 |issue=13 |pages=3079–3090 |doi=10.1158/1078-0432.CCR-19-2744 |pmid=32098770 |url=https://aacrjournals.org/clincancerres/article/26/13/3079/82622/Long-term-Consequences-of-Pelvic-Irradiation |access-date=24 October 2024 |issn=1078-0432}}

Pelvic radiation also induces secondary malignancies such as leukemia, lymphoma, bladder cancer, pelvic malignancy, colorectal cancer, bone, and soft-tissue sarcoma with occurrence rates between 0.2 and 1.0% per year for each.

File:Cervix uteri cancer world map - Death - WHO2004.svg death from cervical cancer per 100,000 inhabitants in 2004{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |publisher=World Health Organization |access-date=11 November 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=11 November 2009 }}

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Worldwide, cervical cancer is both the fourth-most common type of cancer and the fourth-most common cause of death from cancer in women, with over 660,000 new cases and around 350,000 deaths in 2022. It is the second-most common cause of female-specific cancer after breast cancer, accounting for around 8% of both total cancer cases and total cancer deaths in women. 88% (2020 figure) of cervical cancers and 90% of deaths occur in low- and middle-income countries (LMICs) and 2% (2020 figure) in high-income countries (HICs).{{rp|p=650}}{{cite journal | vauthors = Kent A | title = HPV Vaccination and Testing | journal = Reviews in Obstetrics & Gynecology | volume = 3 | issue = 1 | pages = 33–34 | date = Winter 2010 | pmid = 20508781 | pmc = 2876324 }} It is the most frequently detected cancer during pregnancy, with an occurrence of 1.5 to 12 for every 100,000 pregnancies.{{cite journal | vauthors = Cordeiro CN, Gemignani ML | title = Gynecologic Malignancies in Pregnancy: Balancing Fetal Risks With Oncologic Safety | journal = Obstetrical & Gynecological Survey | volume = 72 | issue = 3 | pages = 184–193 | date = March 2017 | pmid = 28304416 | pmc = 5358514 | doi = 10.1097/OGX.0000000000000407 }}

The large majority of cervical cancer cases in 2020 (88%) occurred in LMICs, where they account for 17% of all cancers in women, compared with only 2% in high-income countries (HICs). In sub-Saharan Africa, the region with the highest rates of young women living with HIV (WLWH), approximately 20% of cervical cancer cases occur in WLWH. HPV infection is more likely to persist and to progress to cancer in WLWH. Mortality rates vary 50-fold between countries, ranging from <2 per 100 000 women in some HICs to >40 per 100 000 in some countries of sub-Saharan Africa.{{rp|p=650}}

Of the 20 hardest hit countries by cervical cancer, 19 are in Africa.

Australia is on target to eliminate cervical cancer. It anticipates to achieve this in the next 10 years.

In 2022, it is estimated that 942 new cases of cervical cancer will be diagnosed in Australia. In 2022, it is estimated that a female has a 1 in 180 (or 0.56%) risk of being diagnosed with cervical cancer by the age of 85.{{Cite web |date=18 August 2022 |title=Cervical cancer in Australia statistics |url=https://www.canceraustralia.gov.au/cancer-types/cervical-cancer/statistics |access-date=21 January 2023 |website=Australian Government- Cancer Australia}}

In 2020, there were 165 women aged 25–74 who died from cervical cancer, which is a mortality rate of 2 deaths per 100,000 women in the population. Over the 5 years 2016–2020, there were 62 Aboriginal and Torres Strait Islander women aged 25–74 who died from cervical cancer, which is a mortality rate of 7 deaths per 100,000 Indigenous women in the population. Over the 5 years 2016–2020, the age-standardised mortality rate among Aboriginal and Torres Strait Islander women was 3.8 times the rate of non-Indigenous Australians.{{Cite web |title=National Cervical Screening Program monitoring report 2022, Summary |url=https://www.aihw.gov.au/reports/cancer-screening/ncsp-monitoring-2022/summary |access-date=2023-01-21 |website=Australian Institute of Health and Welfare |date=December 2022 |language=en-AU}}

The number of women diagnosed with cervical cancer has dropped on average by 4.5% each year since organised screening began in 1991 (1991–2005).{{cite web|url= http://www.papscreen.org.au/browse.asp?ContainerID=c15|title= Incidence and mortality rates|date= January 1900|url-status= live|archive-url= https://web.archive.org/web/20090912091409/http://www.papscreen.org.au/browse.asp?ContainerID=c15|archive-date=12 September 2009}} Regular twice-yearly Pap tests [this is out of date] can reduce the incidence of cervical cancer up to 90% in Australia, and save 1,200 Australian women from dying from the disease each year.{{cite web |url=http://www.papscreen.org.au/ |title = Papscreen Victoria |access-date=7 March 2011 |url-status=live |archive-url=https://web.archive.org/web/20110314211744/http://www.papscreen.org.au/ |archive-date=14 March 2011 }} It is predicted that because of the success of the primary HPV testing programme there will be fewer than four new cases per 100 000 women annually by 2028.{{cite journal | vauthors = Hall MT, Simms KT, Lew JB, Smith MA, Brotherton JM, Saville M, Frazer IH, Canfell K | title = The projected timeframe until cervical cancer elimination in Australia: a modelling study | journal = The Lancet. Public Health | volume = 4 | issue = 1 | pages = e19–e27 | date = January 2019 | pmid = 30291040 | doi = 10.1016/S2468-2667(18)30183-X | s2cid = 52924713 | doi-access = free }}

An estimated 1,450 Canadians will be diagnosed with cervical cancer in 2022. An estimated 380 will die from it.{{Cite web |date=May 2022 |title=Cervical Cancer statistics |url=https://cancer.ca/en/cancer-information/cancer-types/cervical/statistics |access-date=21 January 2023 |website=Canadian Cancer Society}}

In India, the number of people with cervical cancer is rising, but overall the age-adjusted rates are decreasing.National Cancer Registry Programme under Indian Council of Medical Research Reports{{Cite web|url=https://www.plunes.com/|title=Plunes HealthCare - Surgery Experience Made Easy | Upto 50% Off|website=www.plunes.com}} Usage of condoms in the female population has improved the survival of women with cancers of the cervix.{{cite journal | vauthors = Krishnatreya M, Kataki AC, Sharma JD, Nandy P, Gogoi G | title = Association of educational levels with survival in Indian patients with cancer of the uterine cervix | journal = Asian Pacific Journal of Cancer Prevention | volume = 16 | issue = 8 | pages = 3121–3123 | date = 2015 | pmid = 25921107 | doi = 10.7314/apjcp.2015.16.8.3121 | doi-access = free }}

As of 2022, the World Health Organization announced that "each year in the WHO European Region more than 66 000 women are newly diagnosed with cervical cancer and more than 30 000 die from this preventable disease."{{Cite web |title=The cancer we can eliminate – WHO/Europe urges Member States to consign cervical cancer to history |url=https://www.who.int/europe/news/item/12-09-2022-the-cancer-we-can-eliminate---who-europe-urges-member-states-to-consign-cervical-cancer-to-history |access-date=2023-01-21 |website=www.who.int |language=en}}

{{update section|date=September 2021}}

Cervical cancer is the 12th-most common cancer in women in the UK (around 3,100 women were diagnosed with the disease in 2011) and accounts for 1% of cancer deaths (around 920 died in 2012).{{cite web|title=Cervical cancer statistics |url=http://www.cancerresearchuk.org/cancer-info/cancerstats/types/cervix/|website=Cancer Research UK|access-date=27 October 2014|url-status=live|archive-url=https://web.archive.org/web/20141007131242/http://www.cancerresearchuk.org/cancer-info/cancerstats/types/cervix/ |archive-date=7 October 2014}} With a 42% reduction from 1988 to 1997, the NHS-implemented screening programme has been highly successful, screening the highest-risk age group (25–49 years) every 3 years, and those ages 50–64 every 5 years.{{citation needed|date=May 2021}}

{{update section|date=September 2021}}

An estimated 13,170 new cervical cancers and 4,250 cervical cancer deaths will occur in the United States in 2019.{{Cite web|url=https://seer.cancer.gov/statfacts/html/cervix.html|title=Cancer Stat Facts: Cervical Cancer|website=National Cancer Institute SEER Program|access-date=4 June 2019}} The median age at diagnosis is 50. The rate of new cases in the United States was 7.3 per 100,000 women, based on rates from 2012 to 2016. Cervical cancer deaths decreased by approximately 74% in the last 50 years, largely due to widespread Pap test screening.{{cite journal | vauthors = Armstrong EP | title = Prophylaxis of cervical cancer and related cervical disease: a review of the cost-effectiveness of vaccination against oncogenic HPV types | journal = Journal of Managed Care Pharmacy | volume = 16 | issue = 3 | pages = 217–230 | date = April 2010 | pmid = 20331326 | doi = 10.18553/jmcp.2010.16.3.217 | pmc = 10437588 | s2cid = 14373353 }} The annual direct medical cost of cervical cancer prevention and treatment before the introduction of the HPV vaccine was estimated at $6 billion.

The Nigerian Institute of Medical Research (NIMR) reports that 28 Nigerian women lose their lives daily due to this disease. This alarming statistic underscores the pressing need for better awareness, prevention, and treatment efforts nationally. Numerous Nigerian women lack access to these preventive measures. In many regions of the country, screening tests such as Pap tests and HPV tests are not easily accessible or affordable{{Cite web |date=2023-04-04 |title=Eliminating Cervical Cancer in Nigeria: How Awareness, Infrastructure, and Government Support Can Make a Difference - My Daily News Usa |url=https://mydailynewsusa.com/eliminating-cervical-cancer-in-nigeria-how-awareness-infrastructure-and-government-support-can-make-a-difference/ |access-date=2023-04-15 |language=en-US |archive-date=15 April 2023 |archive-url=https://web.archive.org/web/20230415025948/https://mydailynewsusa.com/eliminating-cervical-cancer-in-nigeria-how-awareness-infrastructure-and-government-support-can-make-a-difference/ |url-status=dead }}{{Cite web |vauthors=Sahana DU |date=2023-04-04 |title=Eliminating Cervical Cancer in Nigeria: How Awareness, Infrastructure, and Government Support Can Make a Difference |url=https://mydailynewsusa.com/eliminating-cervical-cancer-in-nigeria-how-awareness-infrastructure-and-government-support-can-make-a-difference/ |access-date=2023-04-15 |website=My Daily News Usa |archive-date=15 April 2023 |archive-url=https://web.archive.org/web/20230415025948/https://mydailynewsusa.com/eliminating-cervical-cancer-in-nigeria-how-awareness-infrastructure-and-government-support-can-make-a-difference/ |url-status=dead }}

• 400 BCE: Hippocrates noted that cervical cancer was incurable.
• 1925: Hinselmann invented the colposcope.
• 1928: Papanicolaou developed the Papanicolaou technique.
• 1941: Papanicolaou and Traut: Pap test screening began.
• 1946: Aylesbury spatula was developed to scrape the cervix, collecting the sample for the Pap test.
• 1951: First successful in-vitro cell line, HeLa, derived from biopsy of cervical cancer of Henrietta Lacks.
• 1976: Harald zur Hausen and Gisam found HPV DNA in cervical cancer and genital warts; Hausen later won the Nobel Prize for his work.{{cite journal |vauthors=zur Hausen H |title=Papillomaviruses and cancer: from basic studies to clinical application |journal=Nature Reviews. Cancer |volume=2 |issue=5 |pages=342–350 |date=May 2002 |pmid=12044010 |doi=10.1038/nrc798 |s2cid=4991177|doi-access=free }}
• 1988: Bethesda System for reporting Pap results was developed.
• 2006: First HPV vaccine was approved by the FDA.
• 2015: HPV vaccine shown to protect against infection at multiple body sites.{{cite journal |vauthors=Beachler DC, Kreimer AR, Schiffman M, Herrero R, Wacholder S, Rodriguez AC, Lowy DR, Porras C, Schiller JT, Quint W, Jimenez S, Safaeian M, Struijk L, Schussler J, Hildesheim A, Gonzalez P |display-authors=6 |title=Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection |journal=Journal of the National Cancer Institute |volume=108 |issue=1 |pages=djv302 |date=January 2016 |pmid=26467666 |pmc=4862406 |doi=10.1093/jnci/djv302}}
• 2018: Evidence for single-dose protection with HPV vaccine.{{cite journal |vauthors = Kreimer AR, Herrero R, Sampson JN, Porras C, Lowy DR, Schiller JT, Schiffman M, Rodriguez AC, Chanock S, Jimenez S, Schussler J, Gail MH, Safaeian M, Kemp TJ, Cortes B, Pinto LA, Hildesheim A, Gonzalez P |display-authors=6 |title=Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies |journal=Vaccine |volume=36 |issue=32 Pt A |pages=4774–4782 |date=August 2018 |pmid=29366703 |pmc=6054558 |doi=10.1016/j.vaccine.2017.12.078 }}

Epidemiologists working in the early 20th century noted that cervical cancer behaved like a sexually transmitted disease. In summary:

1. Cervical cancer was noted to be common in female sex workers.
2. It was rare in nuns, except for those who had been sexually active before entering the convent (Rigoni in 1841).
3. It was more common in the second wives of men whose first wives had died from cervical cancer.
4. It was rare in Jewish women.{{cite journal |vauthors=Menczer J |title=The low incidence of cervical cancer in Jewish women: has the puzzle finally been solved? |journal=The Israel Medical Association Journal |volume=5 |issue=2 |pages=120–123 |date=February 2003 |pmid=12674663 |url=http://www.ima.org.il/IMAJ/ViewArticle.aspx?year=2003&month=02&page=120 |access-date=28 November 2015 |url-status=live |archive-url=https://web.archive.org/web/20151208145603/http://www.ima.org.il/IMAJ/ViewArticle.aspx?year=2003&month=02&page=120 |archive-date=8 December 2015 }}
5. In 1935, Syverton and Berry discovered a relationship between RPV (Rabbit Papillomavirus) and skin cancer in rabbits.{{cite journal |last1=Syverton |first1=J. T. |last2=Berry |first2= G. P. |title=Carcinoma in the Cottontail Rabbit Following Spontaneous Virus Papilloma (Shope) |journal=Experimental Biology and Medicine |date=1935 |volume=33 |issue=3 |pages=399–400 |doi=10.3181/00379727-33-8386P|s2cid=88311393 }} (HPV is species-specific and therefore cannot be transmitted to rabbits).{{cite book |title=Human Papillomaviruses |date=2007 |location=Lyon, France|url=https://www.ncbi.nlm.nih.gov/books/NBK321758/ |chapter=Studies of Animal Papillomaviruses |volume=90 |last=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans |series=IARC Monographs on the Evaluation of Carcinogenic Risks to Humans}}

These historical observations suggested that cervical cancer could be caused by a sexually transmitted agent. Initial research in the 1940s and 1950s attributed cervical cancer to smegma.{{cite journal | vauthors = Heins HC, Dennis EJ, Pratthomas HR | title = The possible role of smegma in carcinoma of the cervix | journal = American Journal of Obstetrics and Gynecology | volume = 76 | issue = 4 | pages = 726–33; discussion 733–5 | date = October 1958 | pmid = 13583012 | doi = 10.1016/0002-9378(58)90004-8 }} During the 1960s and 1970s it was suspected that infection with herpes simplex virus (HSV) was the cause of the disease. In summary, HSV was seen as a likely cause because it is known to survive in the female reproductive tract, and to be transmitted sexually in a way compatible with known risk factors, such as promiscuity and low socioeconomic status.{{cite journal | vauthors = Alexander ER | title = Possible etiologies of cancer of the cervix other than herpesvirus | journal = Cancer Research | volume = 33 | issue = 6 | pages = 1485–1490 | date = June 1973 | pmid = 4352386 }} Herpes viruses were also implicated in other malignant diseases, including Burkitt's lymphoma, Nasopharyngeal carcinoma, Marek's disease and the Lucké renal adenocarcinoma. HSV was recovered from cervical tumour cells.{{citation needed|date=January 2023}}

A description of human papillomavirus (HPV) by electron microscopy was given in 1949, and HPV-DNA was identified in 1963.{{Cite book|url=https://books.google.com/books?id=IS84In6aguYC&pg=PA6|title=Human Papillomavirus: A Practical Guide for Urologists| vauthors = Rosenblatt A, de Campos Guidi HG |date=6 August 2009|publisher=Springer Science & Business Media|isbn=978-3-540-70974-9}} It was not until the 1980s that HPV was identified in cervical cancer tissue.{{cite journal | vauthors = Dürst M, Gissmann L, Ikenberg H, zur Hausen H | title = A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 12 | pages = 3812–3815 | date = June 1983 | pmid = 6304740 | pmc = 394142 | doi = 10.1073/pnas.80.12.3812 | doi-access = free | bibcode = 1983PNAS...80.3812D }}. It has since been demonstrated that HPV is implicated in virtually all cervical cancers.{{cite journal | vauthors = Lowy DR, Schiller JT | title = Prophylactic human papillomavirus vaccines | journal = The Journal of Clinical Investigation | volume = 116 | issue = 5 | pages = 1167–1173 | date = May 2006 | pmid = 16670757 | pmc = 1451224 | doi = 10.1172/JCI28607 }} Specific viral subtypes implicated are HPV 16, 18, 31, 45 and others.

In work that was initiated in the mid-1980s, the HPV vaccine was developed, in parallel, by researchers at Georgetown University Medical Center, the University of Rochester, the University of Queensland in Australia, and the U.S. National Cancer Institute.{{cite journal |vauthors=McNeil C |title=Who invented the VLP cervical cancer vaccines? |journal=Journal of the National Cancer Institute |volume=98 |issue=7 |page=433 |date=April 2006 |pmid=16595773 |doi=10.1093/jnci/djj144 |doi-access=free}} In 2006, the US Food and Drug Administration (FDA) approved the first preventive HPV vaccine, marketed by Merck & Co. under the trade name Gardasil.{{citation needed|date=January 2023}}

17 November is the Cervical Cancer Elimination Day of Action. The date marks the day in 2020 when WHO launched the Global strategy to accelerate the elimination of cervical cancer as a public health problem, with a resolution passed by 194 countries. In November 2020, the World Health Organization (WHO), under backing from the World Health Assembly, set out a strategy to eliminate cervical cancer by 2050. The strategy involves vaccinating 90% of girls by the age of 15, screening 70% of women by the age of 35 and again by the age of 45, and treating 90% of women identified with cervical disease.{{Cite web |date=16 November 2020 |title=WHO rolls out plan to rid world of cervical cancer, saving millions of lives |url=https://news.un.org/en/story/2020/11/1077752 |access-date=27 November 2020 |website=UN News}} To eliminate cervical cancer, all countries must reach and maintain an incidence rate of below 4 per 100 000 women.

In Australia, Aboriginal women are more than five times more likely to die from cervical cancer than non-Aboriginal women, suggesting that Aboriginal women are less likely to have regular Pap tests.{{cite web | author = Cancer Institute NSW | publisher = NSW Government | archive-url = https://web.archive.org/web/20130411015842/http://www.csp.nsw.gov.au/aboriginal | archive-date = 11 April 2013 | url = http://www.csp.nsw.gov.au/aboriginal | title = Information about cervical screening for Aboriginal women | year = 2013 }} There are several factors that may limit indigenous women from engaging in regular cervical screening practices, including sensitivity in discussing the topic in Aboriginal communities, embarrassment, anxiety and fear about the procedure.{{cite web | vauthors = Romano MA | publisher = Science Network Western Australia | archive-url = https://web.archive.org/web/20130514223512/http://www.sciencewa.net.au/topics/health-a-medicine/item/995-aboriginal-cervical-cancer-rates-parallel-health-inequity.html | archive-date = 14 May 2013 | url = http://www.sciencewa.net.au/topics/health-a-medicine/item/995-aboriginal-cervical-cancer-rates-parallel-health-inequity.html | title = Aboriginal cervical cancer rates parallel health inequity | date = 17 October 2011 }} Difficulty in accessing screening services (for example, transport difficulties) and a lack of female GPs, trained Pap test providers and trained female Aboriginal Health Workers are also issues.

The Australian Cervical Cancer Foundation (ACCF), founded in 2008, promotes 'women's health by eliminating cervical cancer and enabling treatment for women with cervical cancer and related health issues, in Australia and in developing countries.'{{cite web | author = Australian Cervical Cancer Foundation | publisher = Australian Cervical Cancer Foundation | archive-url = https://web.archive.org/web/20130512195946/http://accf.org.au/about/vision.html | archive-date = 12 May 2013 | url = http://accf.org.au/about/vision.html | title = Vision and Mission }} Ian Frazer, one of the developers of the Gardasil cervical cancer vaccine, is the scientific advisor to ACCF.{{cite web | author = Australian Cervical Cancer Foundation | publisher = Australian Cervical Cancer Foundation | archive-url = https://web.archive.org/web/20130512195956/http://accf.org.au/about/ourboard.html | archive-date = 12 May 2013 | url = http://accf.org.au/about/ourboard.html | title = Our People }} Janette Howard, the wife of the then-Prime Minister of Australia, John Howard, was diagnosed with cervical cancer in 1996, and first spoke publicly about the disease in 2006.{{cite web | vauthors = Bradford G | publisher = Australian Broadcasting Corporation | archive-url = https://web.archive.org/web/20121103140141/http://www.abc.net.au/pm/content/2006/s1766104.htm | archive-date = 3 November 2012 | url = http://www.abc.net.au/pm/content/2006/s1766104.htm | date=16 October 2006 | title = Janette Howard speaks on her battle with cervical cancer }}

File:CDC health disparities for cervical cancer PSA.jpg public service announcement about cervical cancer health disparities in the United States.]]

A 2007 survey of American women found 40% had heard of HPV infection and less than half of those knew it causes cervical cancer.{{cite journal | vauthors = Tiro JA, Meissner HI, Kobrin S, Chollette V | title = What do women in the U.S. know about human papillomavirus and cervical cancer? | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 16 | issue = 2 | pages = 288–294 | date = February 2007 | pmid = 17267388 | doi = 10.1158/1055-9965.EPI-06-0756 | doi-access = free }} Over a longitudinal study from 1975 to 2000, it was found that people of lower socioeconomic census brackets had higher rates of late-stage cancer diagnosis and higher morbidity rates. After controlling for stage, there still existed differences in survival rates.{{cite journal | vauthors = Singh GK, Miller BA, Hankey BF, Edwards BK | title = Persistent area socioeconomic disparities in U.S. incidence of cervical cancer, mortality, stage, and survival, 1975–2000 | journal = Cancer | volume = 101 | issue = 5 | pages = 1051–1057 | date = September 2004 | pmid = 15329915 | doi = 10.1002/cncr.20467 | s2cid = 26033629 | doi-access = free }} Women in the US experience stigma around HPV infection, vaccination, and cervical cancer. This is predominantly driven by fear of social judgment and rejection, self-blame, and shame, with notable negative influences from gender and social norms, as both human papillomavirus infection and cervical cancer were stigmatized due to the perception that they arise from reckless behavior such as having multiple sexual partners or neglecting screening.{{cite journal |vauthors=Peterson CE, Silva A, Goben AH, Ongtengco NP, Hu EZ, Khanna D, Nussbaum ER, Jasenof IG, Kim SJ, Dykens JA |date=December 2021 |title=Stigma and cervical cancer prevention: A scoping review of the U.S. literature |url=https://figshare.com/articles/journal_contribution/16926994 |journal=Prev Med |volume=153 |issue= |page=106849 |doi=10.1016/j.ypmed.2021.106849 |pmid=34662598 |s2cid=239027566}}

Transgender men and gender-diverse people who have a cervix (even if partially intact) or have a prior history of cervical cancer or precancerous conditions, and are age 21 or older who have ever had sex with anyone need to get screened for cervical cancer.{{Cite web |title=As a trans man, do I need to get screened for cervical cancer? |url=https://cancer.ca/en/cancer-information/find-cancer-early/screening-in-lgbtq-communities/as-a-trans-man-do-i-need-to-get-screened-for-cervical-cancer |access-date=21 January 2023 |website=Canadian Cancer Society}}{{Cite web |date=2018-06-27 |title=Should trans men have cervical screening tests? |url=https://www.nhs.uk/common-health-questions/sexual-health/should-trans-men-have-cervical-screening-tests/ |access-date=2023-01-21 |website=nhs.uk |language=en}} Transmasculine people are just as likely as cisgender women to have cervical cancer, but are less likely to undergo cervical screening, because of dysphoria, gender disaffirmation or disempowerment of the individual by healthcare providers,{{cite journal | vauthors = Peitzmeier SM, Bernstein IM, McDowell MJ, Pardee DJ, Agénor M, Alizaga NM, Reisner SL, Potter J | display-authors = 6 | title = Enacting power and constructing gender in cervical cancer screening encounters between transmasculine patients and health care providers | journal = Culture, Health & Sexuality | volume = 22 | issue = 12 | pages = 1315–1332 | date = December 2020 | pmid = 31661659 | pmc = 7188565 | doi = 10.1080/13691058.2019.1677942 }} or being misinformed of HPV and cervical cancer risks{{cite journal | vauthors = Potter J, Peitzmeier SM, Bernstein I, Reisner SL, Alizaga NM, Agénor M, Pardee DJ | title = Cervical Cancer Screening for Patients on the Female-to-Male Spectrum: a Narrative Review and Guide for Clinicians | journal = Journal of General Internal Medicine | volume = 30 | issue = 12 | pages = 1857–1864 | date = December 2015 | pmid = 26160483 | pmc = 4636588 | doi = 10.1007/s11606-015-3462-8 }} as well as many healthcare providers perceiving transmasculine individuals to be at low risk of cervical cancer.{{cite journal | vauthors = Agénor M, Peitzmeier SM, Bernstein IM, McDowell M, Alizaga NM, Reisner SL, Pardee DJ, Potter J | display-authors = 6 | title = Perceptions of cervical cancer risk and screening among transmasculine individuals: patient and provider perspectives | journal = Culture, Health & Sexuality | volume = 18 | issue = 10 | pages = 1192–1206 | date = October 2016 | pmid = 27142466 | doi = 10.1080/13691058.2016.1177203 | s2cid = 22036018 }}

Transgender women who have not had bottom surgery have no risk of cervical cancer, as they do not have a cervix. Trans women who have had bottom surgery to create a vagina (vaginoplasty) and possibly a cervix, are at a very small risk to develop cancer in the tissues of their neo-vagina or neo-cervix as these tissues are made up of different cells than a cervix in a cisgender woman{{Cite news |date=2019-10-10 |title=I'm trans or non-binary, does this affect my cancer screening? |url=https://www.cancerresearchuk.org/about-cancer/cancer-symptoms/spot-cancer-early/screening/trans-and-non-binary-cancer-screening |access-date=2023-01-21 |website=Cancer Research UK |language=en}}{{Cite web |title=As a trans woman, do I need to get screened for cervical cancer? |url=https://cancer.ca/en/cancer-information/find-cancer-early/screening-in-lgbtq-communities/as-a-trans-woman-do-i-need-to-get-screened-for-cervical-cancer |access-date=21 January 2023 |website=Canadian Cancer Society}} Cervical cancer screening is not necessary in trans women who have undergone vaginoplasty because they do not have a cervix.{{cite journal | vauthors = Labanca T, Mañero I, Pannunzio M | title = Transgender patients: considerations for routine gynecologic care and cancer screening | journal = International Journal of Gynecological Cancer | volume = 30 | issue = 12 | pages = 1990–1996 | date = December 2020 | pmid = 33109526 | doi = 10.1136/ijgc-2020-001860 | s2cid = 225096075 | doi-access = free }}

Intersex people with a cervix are also able to have cervical cancer.{{Cite web |date=2017-10-20 |title=Causes of cervical cancer |url=https://www.nhs.uk/conditions/cervical-cancer/causes/ |access-date=2023-01-21 |website=nhs.uk |language=en}}

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{{Reflist|30em}}

{{Refbegin}}

• {{Cite journal | vauthors = Arbyn M, Castellsagué X, de Sanjosé S, Bruni L, Saraiya M, Bray F, Ferlay J | title = Worldwide burden of cervical cancer in 2008 | journal = Annals of Oncology | volume = 22 | issue = 12 | pages = 2675–2686 | date = December 2011 | pmid = 21471563 | doi = 10.1093/annonc/mdr015 | doi-access = free }}
• {{Cite journal | vauthors = Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R | title = Cancer of the cervix uteri | journal = International Journal of Gynaecology and Obstetrics | volume = 143 | issue = Suppl 2 | pages = 22–36 | date = October 2018 | pmid = 30306584 | doi = 10.1002/ijgo.12611 | doi-access = free }}
• {{Cite journal | vauthors = Chuang LT, Temin S, Camacho R, Dueñas-Gonzalez A, Feldman S, Gultekin M, Gupta V, Horton S, Jacob G, Kidd EA, Lishimpi K, Nakisige C, Nam JH, Ngan HY, Small W, Thomas G, Berek JS | display-authors = 6 | title = Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline | journal = Journal of Global Oncology | volume = 2 | issue = 5 | pages = 311–340 | date = October 2016 | pmid = 28717717 | pmc = 5493265 | doi = 10.1200/JGO.2016.003954 }}
• {{Cite journal | vauthors = Peto J, Gilham C, Fletcher O, Matthews FE | title = The cervical cancer epidemic that screening has prevented in the UK | journal = Lancet | volume = 364 | issue = 9430 | pages = 249–256 | year = 2004 | pmid = 15262102 | doi = 10.1016/S0140-6736(04)16674-9 | s2cid = 11059712 }}
• {{Cite journal | vauthors = Pimenta JM, Galindo C, Jenkins D, Taylor SM | title = Estimate of the global burden of cervical adenocarcinoma and potential impact of prophylactic human papillomavirus vaccination | journal = BMC Cancer | volume = 13 | issue = 1 | page = 553 | date = November 2013 | pmid = 24261839 | pmc = 3871005 | doi = 10.1186/1471-2407-13-553 | doi-access = free }}

{{Refend}}

{{Commons category}}

• [https://www.who.int/news-room/fact-sheets/detail/cervical-cancer Fact sheet on cervical cancer] by the WHO
• [https://www.cancer.gov/types/cervical Cervical cancer] at the NIH National Cancer Institute
• [https://www.jostrust.org.uk/ Jo's Cervical Cancer Trust], UK cervical cancer charity

{{Medical resources

| DiseasesDB = 2278

| ICD10 = {{ICD10|C|53||c|51}}

| ICD9 = {{ICD9|180}}

| ICDO =

| OMIM = 603956

| MedlinePlus = 000893

| eMedicineSubj = med

| eMedicineTopic = 324

| eMedicine_mult = {{eMedicine2|radio|140}}

| MeshID = D002583

}}

{{Human papillomavirus}}

{{Female genital neoplasia}}

{{Authority control}}

{{DEFAULTSORT:Cervical Cancer}}

Category:Cervical cancer

Category:Gynaecological cancer

Category:Infectious causes of cancer

Category:Papillomavirus-associated diseases

Category:Sexually transmitted diseases and infections

Category:Wikipedia medicine articles ready to translate