Sections

Medication

Medication Summary

Chemotherapy should be administered in conjunction with radiation therapy to most patients with stage IB (high-risk) to stage IVA cervical cancer. Cisplatin is the agent used most commonly, although 5-fluorouracil also is used frequently. For patients with metastatic disease, cisplatin remains the most active agent. Topotecan, ifosfamide, and paclitaxel also have significant activity in this setting. The combination of topotecan and cisplatin improves overall survival. However, acute toxicities are also increased.

Class Summary

Alkylating chemotherapy agents inhibit cell growth and proliferation. They inhibit DNA synthesis through the formation of DNA cross-links.

Cisplatin (Platinol)

View full drug information

Intrastrand cross-linking of DNA and inhibition of DNA precursors are among the proposed mechanisms of action for cisplatin. This agent is used in combination with radiation therapy.

Ifosfamide (Ifex)

View full drug information

Ifosfamide forms DNA interstrand and intrastrand bonds that interfere with protein synthesis. Although the US Food and Drug Administration (FDA) has approved this agent only for the treatment of testicular cancer, it has several off-label indications, including treatment of cervical cancer.

Class Summary

Antimetabolite antineoplastic agents inhibit cell growth and proliferation. They interfere with DNA synthesis by blocking the methylation of deoxyuridylic acid.

Fluorouracil (Adrucil)

View full drug information

Fluorouracil is a pyrimidine antimetabolite. Several mechanisms of action have been proposed, including inhibition of thymidylate synthase and inhibition of RNA synthesis. This agent is also a potent radiosensitizer.

Class Summary

Antimicrotubular antineoplastic agents prevent cell growth and proliferation. They work by enhancing tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly.

Paclitaxel (Taxol)

View full drug information

The mechanisms of action of paclitaxel are tubulin polymerization and microtubule stabilization. This agent also participates in the breakage of chromosomes and modulation of immune response.

Class Summary

Topoisomerase-inhibiting antineoplastic agents prevent cell growth and proliferation. They work by binding to topoisomerase and causing single-strand DNA breaks.

Topotecan (Hycamtin)

View full drug information

Topotecan inhibits topoisomerase I, inhibiting DNA replication. It acts in the S phase of the cell cycle. Patients who have received prior chemotherapy should be given a lower dose initially.

Class Summary

Vascular endothelial growth factor (VEGF) is crucial to angiogenesis. VEGF inhibitors directly bind to the VEGF protein to disrupt angiogenesis.

Bevacizumab (Avastin)

View full drug information

Bevacizumab is a recombinant humanized monoclonal antibody to VEGF. It blocks the angiogenic molecule VEGF, thereby inhibiting tumor angiogenesis and starving the tumor of blood and nutrients. It is indicated as part of a combination chemotherapy regimen for persistent, recurrent, or metastatic carcinoma of the cervix.

Class Summary

Monoclonal antibodies that bind the programmed cell death-1 protein (PD-1) ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production.

Pembrolizumab (Keytruda)

View full drug information

Indicated for treatment of recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1 or greater) as determined by an FDA-approved test. Pembrolizumab is also indicated for unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mut/Mb] solid tumors in patients that have progressed following prior treatment and who have no alternative treatment options.

Class Summary

The 9-valent HPV vaccine is indicated for prevention of HPV-associated neoplasias and precancerous genital lesions. The 2-valent and 4-valent vaccines were discontinued from the US market in 2016.

Children and adolescents aged 15 years and younger need two, not three, doses of the HPV vaccine; this ACIP recommendation stems from the vaccine’s enhanced immunogenicity in preteens and adolescents aged 9-14 years. The schedule for older adolescents and young adults aged 15 through 45 years is three inoculations within 6 months.

Human papillomavirus vaccine, nonavalent (Gardasil 9)

View full drug information

Recombinant vaccine that targets 9 HPV types (6, 11, 16, 18, 31, 33, 45, 52, and 58). It is indicated for females aged 9 through 45 years to prevent cervical, vulvar, vaginal, and anal cancer. It is also indicated to prevent genital warts and dysplastic lesions (eg, cervical, vulvar, vaginal, anal). It is also indicated for males aged 9 through 45 years for prevention of neoplasias and dysplasias (eg, anal cancer).

Human papillomavirus vaccine, bivalent (Cervarix)

View full drug information

October 21, 2016: HPV bivalent vaccine discontinued in the United States.

The bivalent recombinant HPV vaccine is prepared from the L1 protein of HPV types 16 and 18. It is indicated for girls and women (ages 9-25 years) to prevent the following diseases caused by oncogenic HPV types 16 and 18:

- Cervical cancer

- CIN grade 2 or higher

- Cervical adenocarcinoma in situ

- CIN grade 1

Questions

Updated Guideline on Cervical Cancer Screening Issued by ACOG. Pap tests less frequent under new guidelines. Medscape Medical News. Available at http://www.medscape.com/viewarticle/773282. December 24, 2015; Accessed: February 25, 2016.
[Guideline] American College of Obstetricians and Gynecologists. Practice Bulletin No. 157: Cervical Cancer Screening and Prevention. Obstet Gynecol. 2016 Jan. 127 (1):e1-e20. [QxMD MEDLINE Link].
[Guideline] Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin. 2012 May-Jun. 62(3):147-72. [QxMD MEDLINE Link].
Moyer VA, U.S. Preventive Services Task Force. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012 Jun 19. 156 (12):880-91, W312. [QxMD MEDLINE Link]. [Full Text].
Immunogenicity and Tolerability of Broad Spectrum Human Papillomavirus (HPV) Vaccine in Adult and Young Adult Women (V503-004) - NCT03158220. ClinicalTrials.gov. March 13, 2018; Accessed: 2018 Oct 11.
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Cervical Cancer Version 1.2016. Available at http://www.nccn.org/professionals/physician_gls/PDF/cervical.pdf. Accessed: January 21, 2016.
[Guideline] American Society for Colposcopy and Cervical Pathology. 2006 Consensus Guidelines. Available at http://www.asccp.org/ConsensusGuidelines/tabid/7436/Default.aspx. Accessed: August 18, 2011.
National Cancer Institute. Oral Contraceptives and Cancer Risk. Available at http://www.cancer.gov/cancertopics/factsheet/Risk/oralcontraceptives. Accessed: April 16, 2012.
Magnusson PK, Sparen P, Gyllensten UB. Genetic link to cervical tumours. Nature. 1999 Jul 1. 400(6739):29-30. [QxMD MEDLINE Link].
Galloway DA. Papillomavirus vaccines in clinical trials. Lancet Infect Dis. 2003 Aug. 3(8):469-75. [QxMD MEDLINE Link].
Ghaderi M, Nikitina L, Peacock CS, et al. Tumor necrosis factor a-11 and DR15-DQ6 (B*0602) haplotype increase the risk for cervical intraepithelial neoplasia in human papillomavirus 16 seropositive women in Northern Sweden. Cancer Epidemiol Biomarkers Prev. 2000 Oct. 9(10):1067-70. [QxMD MEDLINE Link].
Stanczuk GA, Sibanda EN, Tswana SA, Bergstrom S. Polymorphism at the -308-promoter position of the tumor necrosis factor-alpha (TNF-alpha) gene and cervical cancer. Int J Gynecol Cancer. 2003 Mar-Apr. 13(2):148-53. [QxMD MEDLINE Link].
Govan VA, Constant D, Hoffman M, Williamson AL. The allelic distribution of -308 Tumor Necrosis Factor-alpha gene polymorphism in South African women with cervical cancer and control women. BMC Cancer. 2006 Jan 26. 6:24. [QxMD MEDLINE Link]. [Full Text].
Abrahamsson J, Carlsson B, Mellander L. Tumor necrosis factor-alpha in malignant disease. Am J Pediatr Hematol Oncol. 1993 Nov. 15(4):364-9. [QxMD MEDLINE Link].
Yang YC, Chang CL, Chen ML. Effect of p53 polymorphism on the susceptibility of cervical cancer. Gynecol Obstet Invest. 2001. 51(3):197-201. [QxMD MEDLINE Link].
Storey A, Thomas M, Kalita A, et al. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature. 1998 May 21. 393(6682):229-34. [QxMD MEDLINE Link].
Andersson S, Rylander E, Strand A, Sallstrom J, Wilander E. The significance of p53 codon 72 polymorphism for the development of cervical adenocarcinomas. Br J Cancer. 2001 Oct 19. 85(8):1153-6. [QxMD MEDLINE Link]. [Full Text].
Kim JW, Lee CG, Park YG, et al. Combined analysis of germline polymorphisms of p53, GSTM1, GSTT1, CYP1A1, and CYP2E1: relation to the incidence rate of cervical carcinoma. Cancer. 2000 May 1. 88(9):2082-91. [QxMD MEDLINE Link].
Lee SA, Kim JW, Roh JW, et al. Genetic polymorphisms of GSTM1, p21, p53 and HPV infection with cervical cancer in Korean women. Gynecol Oncol. 2004 Apr. 93(1):14-8. [QxMD MEDLINE Link].
Wank R, Meulen JT, Luande J, Eberhardt HC, Pawlita M. Cervical intraepithelial neoplasia, cervical carcinoma, and risk for patients with HLA-DQB1*0602,*301,*0303 alleles. Lancet. 1993 May 8. 341(8854):1215. [QxMD MEDLINE Link].
Engelmark M, Beskow A, Magnusson J, Erlich H, Gyllensten U. Affected sib-pair analysis of the contribution of HLA class I and class II loci to development of cervical cancer. Hum Mol Genet. 2004 Sep 1. 13(17):1951-8. [QxMD MEDLINE Link].
Sastre-Garau X, Cartier I, Jourdan-Da Silva N, De Cremoux P, Lepage V, Charron D. Regression of low-grade cervical intraepithelial neoplasia in patients with HLA-DRB1*13 genotype. Obstet Gynecol. 2004 Oct. 104(4):751-5. [QxMD MEDLINE Link].
Mahmud SM, Robinson K, Richardson H, et al. HLA polymorphisms and cervical human Papillomavirus infection in a cohort of Montreal University students. J Infect Dis. 2007 Jul 1. 196(1):82-90. [QxMD MEDLINE Link].
Chatterjee K, Dandara C, Hoffman M, Williamson AL. CCR2-V64I polymorphism is associated with increased risk of cervical cancer but not with HPV infection or pre-cancerous lesions in African women. BMC Cancer. 2010 Jun 10. 10:278. [QxMD MEDLINE Link]. [Full Text].
Coelho A, Matos A, Catarino R, et al. The influence of chemokine receptor CCR2 genotypes in the route to cervical carcinogenesis. Gynecol Obstet Invest. 2007. 64(4):208-12. [QxMD MEDLINE Link].
Lai HC, Sytwu HK, Sun CA, et al. Single nucleotide polymorphism at Fas promoter is associated with cervical carcinogenesis. Int J Cancer. 2003 Jan 10. 103(2):221-5. [QxMD MEDLINE Link].
Sun T, Gao Y, Tan W, et al. A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers. Nat Genet. 2007 May. 39(5):605-13. [QxMD MEDLINE Link].
Sova P, Feng Q, Geiss G, et al. Discovery of novel methylation biomarkers in cervical carcinoma by global demethylation and microarray analysis. Cancer Epidemiol Biomarkers Prev. 2006 Jan. 15(1):114-23. [QxMD MEDLINE Link].
Feng Q, Balasubramanian A, Hawes SE, et al. Detection of hypermethylated genes in women with and without cervical neoplasia. J Natl Cancer Inst. 2005 Feb 16. 97(4):273-82. [QxMD MEDLINE Link].
de Sanjose S, Quint WG, Alemany L, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010 Nov. 11(11):1048-56. [QxMD MEDLINE Link].
Bouvard V, Baan R, Straif K, et al. A review of human carcinogens--Part B: biological agents. Lancet Oncol. 2009 Apr. 10(4):321-2. [QxMD MEDLINE Link].
HIV Infection and Cancer Risk. National Cancer Institute. Available at http://www.cancer.gov/cancertopics/factsheet/Risk/hiv-infection. Accessed: February 28, 2012.
[Guideline] American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 61, April 2005. Human papillomavirus. Obstet Gynecol. 2005 Apr. 105 (4):905-18. [QxMD MEDLINE Link].
Arends MJ, Wyllie AH, Bird CC. Papillomaviruses and human cancer. Hum Pathol. 1990 Jul. 21(7):686-98. [QxMD MEDLINE Link].
Schiffman MH, Bauer HM, Hoover RN, et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst. 1993 Jun 16. 85(12):958-64. [QxMD MEDLINE Link].
Liebrich C, Brummer O, Von Wasielewski R, et al. Primary cervical cancer truly negative for high-risk human papillomavirus is a rare but distinct entity that can affect virgins and young adolescents. Eur J Gynaecol Oncol. 2009. 30(1):45-8. [QxMD MEDLINE Link].
Hoover RN, Hyer M, Pfeiffer RM, et al. Adverse health outcomes in women exposed in utero to diethylstilbestrol. N Engl J Med. 2011 Oct 6. 365(14):1304-14. [QxMD MEDLINE Link].
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr. 61(2):69-90. [QxMD MEDLINE Link].
American Cancer Society. Cancer Facts & Figures 2012. Available at http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2012. Accessed: February 28, 2012.
Solomon D, Breen N, McNeel T. Cervical cancer screening rates in the United States and the potential impact of implementation of screening guidelines. CA Cancer J Clin. 2007 Mar-Apr. 57(2):105-11. [QxMD MEDLINE Link].
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan. 72 (1):7-33. [QxMD MEDLINE Link]. [Full Text].
World Health Organization. WHO/ICO information centre on human papilloma virus (HPV) and cervical cancer. Available at http://www.who.int/hpvcentre/statistics/en. Accessed: February 28, 2012.
Forouzanfar MH, Foreman KJ, Delossantos AM, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet. 2011 Oct 22. 378(9801):1461-84. [QxMD MEDLINE Link].
Henley SJ, King JB, German RR, Richardson LC, Plescia M. Surveillance of screening-detected cancers (colon and rectum, breast, and cervix) - United States, 2004-2006. MMWR Surveill Summ. 2010 Nov 26. 59(9):1-25. [QxMD MEDLINE Link].
Vinh-Hung V, Bourgain C, Vlastos G, et al. Prognostic value of histopathology and trends in cervical cancer: a SEER population study. BMC Cancer. 2007 Aug 23. 7:164. [QxMD MEDLINE Link]. [Full Text].
Vinokurova S, Wentzensen N, Kraus I, et al. Type-dependent integration frequency of human papillomavirus genomes in cervical lesions. Cancer Res. 2008 Jan 1. 68(1):307-13. [QxMD MEDLINE Link].
Porras C, Rodriguez AC, Hildesheim A, et al. Human papillomavirus types by age in cervical cancer precursors: predominance of human papillomavirus 16 in young women. Cancer Epidemiol Biomarkers Prev. 2009 Mar. 18(3):863-5. [QxMD MEDLINE Link]. [Full Text].
Surveillance Epidemiology and End Results. SEER Stat Fact Sheets: Cervix Uteri. National Cancer Institute. Available at http://seer.cancer.gov/statfacts/html/cervix.html. Accessed: April 16, 2012.
Everett T, Bryant A, Griffin MF, Martin-Hirsch PP, Forbes CA, Jepson RG. Interventions targeted at women to encourage the uptake of cervical screening. Cochrane Database Syst Rev. 2011 May 11. CD002834. [QxMD MEDLINE Link].
Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet. 2009 May. 105(2):107-8. [QxMD MEDLINE Link].
[Guideline] Qaseem A, Humphrey LL, Harris R, Starkey M, Denberg TD. Screening pelvic examination in adult women: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014 Jul 1. 161(1):67-72. [QxMD MEDLINE Link]. [Full Text].
Bankhead C. ACP: no need for routine pelvic exams. MedPage Today. June 30, 2014. [Full Text].
Bloomfield HE, Olson A, Greer N, et al. Screening pelvic examinations in asymptomatic, average-risk adult women: an evidence report for a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014 Jul 1. 161(1):46-53. [QxMD MEDLINE Link]. [Full Text].
Sawaya GF, Kulasingam S, Denberg TD, Qaseem A, Clinical Guidelines Committee of American College of Physicians. Cervical Cancer Screening in Average-Risk Women: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015 Jun 16. 162 (12):851-9. [QxMD MEDLINE Link].
U.S. Preventive Services Task Force. Cervical Cancer: Screening. U.S. Preventive Services Task Force Draft Recommendation Statement. Available at https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/cervical-cancer-screening2. September 2017; Accessed: January 25, 2018.
Barclay L. Cervical screening guidelines updated. Medscape Medical News from WebMD. March 21, 2013. Available at http://www.medscape.com/viewarticle/781190. Accessed: April 5, 2013.
Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis. 2013 Apr. 17(5 Suppl 1):S1-S27. [QxMD MEDLINE Link].
Castle PE, Kinney WK, Xue X, Cheung LC, Gage JC, Zhao FH, et al. Effect of Several Negative Rounds of Human Papillomavirus and Cytology Co-testing on Safety Against Cervical Cancer: An Observational Cohort Study. Ann Intern Med. 2018 Jan 2. 168 (1):20-29. [QxMD MEDLINE Link].
Siebers AG, Klinkhamer PJ, Vedder JE, Arbyn M, Bulten J. Causes and relevance of unsatisfactory and satisfactory but limited smears of liquid-based compared with conventional cervical cytology. Arch Pathol Lab Med. 2012 Jan. 136(1):76-83. [QxMD MEDLINE Link].
Chen YB, Hu CM, Chen GL, Hu D, Liao J. Staging of uterine cervical carcinoma: whole-body diffusion-weighted magnetic resonance imaging. Abdom Imaging. 2011 Oct. 36(5):619-26. [QxMD MEDLINE Link].
Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002 Apr 24. 287(16):2114-9. [QxMD MEDLINE Link].
Wang J, Andrae B, Sundström K, Ström P, Ploner A, Elfström KM, et al. Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study. BMJ. 2016 Feb 11. 352:i276. [QxMD MEDLINE Link].
American Joint Committee on Cancer. Cervix uteri. Greene FL, Page DL, Fleming ID, et al, eds. AJCC Cancer Staging Manual. 6th ed. New York: Springer; 2002. 259-65.
Rahangdale L, Lippmann QK, Garcia K, Budwit D, Smith JS, van Le L. Topical 5-fluorouracil for treatment of cervical intraepithelial neoplasia 2: a randomized controlled trial. Am J Obstet Gynecol. 2014 Apr. 210(4):314.e1-8. [QxMD MEDLINE Link].
Brown T. 5-fluorouracil effective treatment for CIN 2 in small trial. Medscape Medical News from WebMD. Jaunary 9, 2014. Available at http://www.medscape.com/viewarticle/818985. Accessed: January 19, 2014.
Speiser D, Mangler M, Kohler C, et al. Fertility outcome after radical vaginal trachelectomy: a prospective study of 212 patients. Int J Gynecol Cancer. 2011 Dec. 21(9):1635-9. [QxMD MEDLINE Link].
Lakhman Y, Akin O, Park KJ, et al. Stage IB1 cervical cancer: role of preoperative MR imaging in selection of patients for fertility-sparing radical trachelectomy. Radiology. 2013 Oct. 269(1):149-58. [QxMD MEDLINE Link].
Beiner ME, Hauspy J, Rosen B, et al. Radical vaginal trachelectomy vs. radical hysterectomy for small early stage cervical cancer: a matched case-control study. Gynecol Oncol. 2008 Aug. 110(2):168-71. [QxMD MEDLINE Link].
Lowe MP, Chamberlain DH, Kamelle SA, Johnson PR, Tillmanns TD. A multi-institutional experience with robotic-assisted radical hysterectomy for early stage cervical cancer. Gynecol Oncol. 2009 May. 113(2):191-4. [QxMD MEDLINE Link].
Nezhat FR, Datta MS, Liu C, Chuang L, Zakashansky K. Robotic radical hysterectomy versus total laparoscopic radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. JSLS. 2008 Jul-Sep. 12(3):227-37. [QxMD MEDLINE Link]. [Full Text].
Cantrell LA, Mendivil A, Gehrig PA, Boggess JF. Survival outcomes for women undergoing type III robotic radical hysterectomy for cervical cancer: a 3-year experience. Gynecol Oncol. 2010 May. 117(2):260-5. [QxMD MEDLINE Link].
Shah M, Lewin SN, Deutsch I, et al. Therapeutic role of lymphadenectomy for cervical cancer. Cancer. 2011 Jan 15. 117(2):310-7. [QxMD MEDLINE Link].
Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study. Gynecol Oncol. 1999 May. 73(2):177-83. [QxMD MEDLINE Link].
Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr. 18(8):1606-13. [QxMD MEDLINE Link].
Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15. 340(15):1137-43. [QxMD MEDLINE Link].
Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15. 340(15):1144-53. [QxMD MEDLINE Link].
Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15. 340(15):1154-61. [QxMD MEDLINE Link].
ACOG practice bulletin. Diagnosis and treatment of cervical carcinomas. Number 35, May 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002 Jul. 78(1):79-91. [QxMD MEDLINE Link].
Long HJ 3rd, Bundy BN, Grendys EC Jr, et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005 Jul 20. 23(21):4626-33. [QxMD MEDLINE Link].
Monk BJ, Sill MW, McMeekin DS, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009 Oct 1. 27(28):4649-55. [QxMD MEDLINE Link]. [Full Text].
Berek JS, Howe C, Lagasse LD, Hacker NF. Pelvic exenteration for recurrent gynecologic malignancy: survival and morbidity analysis of the 45-year experience at UCLA. Gynecol Oncol. 2005 Oct. 99(1):153-9. [QxMD MEDLINE Link].
Goldberg GL, Sukumvanich P, Einstein MH, Smith HO, Anderson PS, Fields AL. Total pelvic exenteration: the Albert Einstein College of Medicine/Montefiore Medical Center Experience (1987 to 2003). Gynecol Oncol. 2006 May. 101(2):261-8. [QxMD MEDLINE Link].
Moore DH. Chemotherapy for advanced, recurrent, and metastatic cervical cancer. J Natl Compr Canc Netw. 2008 Jan. 6(1):53-7. [QxMD MEDLINE Link].
Moore DH, Blessing JA, McQuellon RP, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1. 22(15):3113-9. [QxMD MEDLINE Link].
Moore KN, Herzog TJ, Lewin S, et al. A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer. Gynecol Oncol. 2007 May. 105(2):299-303. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA approves Avastin to treat patients with aggressive and late-stage cervical cancer [news release]. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm410121.htm. Accessed: August 15, 2014.
Lowes R. FDA OKs bevacizumab (Avastin) for late-stage cervical cancer. Medscape Medical News from WebMD. August 14, 2014. Available at http://www.medscape.com/viewarticle/829985. Accessed: August 20, 2014.
Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20. 370(8):734-43. [QxMD MEDLINE Link].
Mulcahy N. Bevacizumab changes practice in advanced cervical cancer. Medscape Medical News from WebMD. February 19, 2014. Available at http://www.medscape.com/viewarticle/820815. Accessed: February 25, 2014.
Chustecka Z. Bevacizumab prolongs survival in advanced cervical cancer. Medscape Medical News from WebMD. June 2, 2013. Available at http://www.medscape.com/viewarticle/805172. Accessed: June 24, 2013.
Tewari KS, Sill M, Long HJ, et al. Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: A phase III randomized trial of the Gynecologic Oncology Group. Asco University. Available at http://meetinglibrary.asco.org/content/116712-132. Accessed: June 24, 2013.
Keytruda (pembrolizumab) [package insert]. Whitehouse Station, NJ: Merck and Co, Inc. 2018 June. Available at [Full Text].
Keytruda (pembrolizumab) [package insert]. Whitehouse Station, NJ: Merck & Co, Inc. June 2020. Available at [Full Text].
Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003 Feb 1. 157(3):218-26. [QxMD MEDLINE Link].
Repp KK, Nielson CM, Fu R, et al. Male human papillomavirus prevalence and association with condom use in Brazil, Mexico, and the United States. J Infect Dis. 2012 Apr. 205(8):1287-93. [QxMD MEDLINE Link]. [Full Text].
Roberts JN, Buck CB, Thompson CD, et al. Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan. Nat Med. 2007 Jul. 13(7):857-61. [QxMD MEDLINE Link].
Munoz N, Kjaer SK, Sigurdsson K, et al. Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women. J Natl Cancer Inst. 2010 Mar 3. 102(5):325-39. [QxMD MEDLINE Link].
Lehtinen M, Paavonen J, Wheeler CM, et al. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012 Jan. 13(1):89-99. [QxMD MEDLINE Link].
Wheeler CM, Castellsague X, Garland SM, et al. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012 Jan. 13(1):100-10. [QxMD MEDLINE Link].
FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm426485.htm. December. 10, 2014; Accessed: February 25, 2016.
U.S. Food and Drug Administration. FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old. FDA News Release. 2018 Oct 05. Available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622715.htm.
Centers for Disease Control and Prevention. ACIP Recommendations. Available at http://www.cdc.gov/vaccines/pubs/ACIP-list.htm#hpv. Accessed: April 17, 2012.
Catch-Up Immunization Schedule for Persons Aged 4 Months Through 18 Years Who Start Late or Who Are More Than 1 Month Behind. Centers for Disease Control and Prevention (CDC). Available at https://www.cdc.gov/vaccines/schedules/hcp/imz/catchup.html. 2018 Feb 06;
Brooks M. One HPV shot may be enough to protect against cervical cancer. Medscape Medical News from WebMD. November 4, 2013. Available at http://www.medscape.com/viewarticle/813780. Accessed: November 13, 2013.
Safaeian M, Porras C, Pan Y, et al. Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica vaccine trial. Cancer Prev Res (Phila). 2013 Nov. 6(11):1242-50. [QxMD MEDLINE Link].
Roteli-Martins CM, Naud P, De Borba P, et al. Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother. 2012 Mar. 8(3):390-7. [QxMD MEDLINE Link].
Slade BA, Leidel L, Vellozzi C, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA. 2009 Aug 19. 302(7):750-7. [QxMD MEDLINE Link].
Huh WK, Ault KA, Chelmow D, Davey DD, Goulart RA, Garcia FA, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. J Low Genit Tract Dis. 2015 Apr. 19 (2):91-6. [QxMD MEDLINE Link].
US Preventive Services Task Force. Screening for Cervical Cancer US Preventive Services Task Force Recommendation Statement. JAMA. 2018. 320(7):674-686.
[Guideline] American College of Obstetricians and Gynecologists. Practice Bulletin No. 140: management of abnormal cervical cancer screening test results and cervical cancer precursors. Obstet Gynecol. 2013 Dec. 122 (6):1338-67. [QxMD MEDLINE Link].
[Guideline] Petrosky E, Bocchini JA Jr, Hariri S, Chesson H, Curtis CR, Saraiya M, et al. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2015 Mar 27. 64 (11):300-4. [QxMD MEDLINE Link]. [Full Text].
Koh WJ, Abu-Rustum NR, Bean S, et al. Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019 Jan. 17 (1):64-84. [QxMD MEDLINE Link].
[Guideline] Colombo N, Carinelli S, Colombo A, Marini C, Rollo D, Sessa C, et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012 Oct. 23 Suppl 7:vii27-32. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013 Jul 1. 31 (19):2500-10. [QxMD MEDLINE Link].
Chuang LT, Temin S, Camacho R, et al. Management and Care of Women With Invasive Cervical Cancer Resource-Stratified Guideline. American Society of Clinical Oncology. Available at http://www.asco.org/practice-guidelines/quality-guidelines/guidelines/gynecologic-cancer#/11801. May 25, 2016; Accessed: May 31, 2016.
Nelson R. ASCO Issues First Ever Practice Guideline for Cervical Cancer. Medscape Medical News. Available at http://www.medscape.com/viewarticle/863794. May 25, 2016; Accessed: May 31, 2016.
Gardasil. U.S. Food and Drug Administration. Available at http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM094042. Accessed: February 28, 2012.
FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2010 May 28. 59(20):626-9. [QxMD MEDLINE Link].

Media Gallery

Cervical carcinoma with adnexa.
Squamous cell cervical carcinoma.
Cervical intraepithelial neoplasia grade I.
Cervical intraepithelial neoplasia grade III.
CT scan of cervical cell carcinoma demonstrates markedly enlarged lymph node at left pelvic sidewall. This is consistent with pelvic lymph node metastasis, which is indicative of stage IIIB disease. Cystic consistency is not unusual for metastatic cervical carcinoma. Primary tumor is well depicted as hypoattenuating circumscribed mass. Cyst is present in anteriorly located left ovary.

of 5

Table 1. Human Papillomavirus Types Associated With Cervical Cancer

HPV Alpha Group	Types	Evidence for Cervical Cancer Causation
1	16	Most carcinogenic HPV type, known to cause cancer at several sites
1	18,31,33,35,39,45,51,52,56,58, 59	Sufficient evidence
2A	68	Limited evidence in humans and strong mechanistic evidence
2B	26,53,66,67,70,73,82	Limited evidence in humans
2B	30,34,69,85,97	Classified by phylogenetic analogy to HPV types with sufficient or limited evidence in humans
3	6,11	Inadequate epidemiological evidence and absence of carcinogenic potential in mechanistic studies
HPV = human papillomavirus.

Table 2. Cervical Cancer Staging: Primary Tumor (T)

TNM Stage	FIGO Stage
TX	-	Primary tumor cannot be assessed
T0	-	No evidence of primary tumor
Tis	0	Carcinoma in situ
T1	I	Cervical carcinoma confined to uterus (extension to corpus should be disregarded)
T1a	IA	Invasive carcinoma diagnosed only by microscopy. All macroscopically visible lesions—even with superficial invasion—are T1b/1B. Stromal invasion with a maximal depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less. Vascular space involvement, venous or lymphatic, does not affect classification.
T1a1	IA1	Measured stromal invasion 3 mm or less in depth and 7 mm or less in lateral spread
T1a2	IA2	Measured stromal invasion more than 3 mm but not more than 5 mm with a horizontal spread 7 mm or less
T1b	IB	Clinically visible lesion confined to the cervix or microscopic lesion greater than IA2
T1b1	IB1	Clinically visible lesion 4 cm or less in greatest dimension
	IB2	Clinically visible lesion more than 4 cm
T2	II	Cervical carcinoma extends beyond the cervix but not to the pelvic sidewall or to the lower third of vagina
T2a	IIA	Tumor without parametrial invasion
T2b	IIB	Tumor with parametrial invasion
T3	III	Tumor extends to the pelvic wall and/or involves the lower third of the vagina and/or causes hydronephrosis or nonfunctioning kidney
T3a	IIIA	Tumor involves lower third of vagina; no extension to pelvic sidewall
T3b	IIIB	Tumor extends to pelvic sidewall and/or causes hydronephrosis or nonfunctioning kidney
-	IV	Cervical carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the bladder mucosa or rectal mucosa. Bullous edema does not qualify as a criteria for stage IV disease.
T4	IVA	Spread to mucosa of adjacent organs (bladder, rectum, or both)
M1	IVB	Distant metastasis

Table 3. UICC/AJCC Staging for Cervical Cancer

Stage	Tumor	Node	Metastasis
0	Tis	N0	M0
IA1	T1a1	N0	M0
IA2	T1a2	N0	M0
IB1	T1b1	N0	M0
IIA	T2a	N0	M0
IIB	T2b	N0	M0
IIIA	T3a	N0	M0
IIIB	T1	N1	M0
-	T2	N1	M0
-	T3a	N1	M0
-	T3b	Any N	M0
IVA	T4	Any N	M0
IVB	Any T	Any N	M1

Table. 1

Patient Status	Recommended Screening Method	Comments
< 21 years old	No screening	Sexual history is not a consideration
21-29 years old	Cytology alone every 3 years
30-65 years old	Preferred: HPV and cytology co-testing every 5 years Acceptable: Cytology alone every 3 years
>65 years old	Screening can be discontinued after either three consecutive negative cytology tests or two negative cytology and HPV tests within 10 years, provided the most recent test was within 5 years	Women with a history of cervical intraepithelial neoplasia (CIN) 2, CIN 3, or adenocarcinoma in situ should continue routine age-based screening for at least 20 years
After total hysterectomy	No screening necessary	Applies to women without a cervix and without a history of CIN 2, CIN 3, adenocarcinoma in situ, or cancer in the past 20 years
After HPV vaccination	Follow the same age-specific recommendations as unvaccinated women

Back to List

Author

Cecelia H Boardman, MD Virginia Gynecologic Oncology

Cecelia H Boardman, MD is a member of the following medical societies: Society of Gynecologic Oncology, American College of Obstetricians and Gynecologists, American College of Surgeons, Minnesota Medical Association

Disclosure: Received salary from Merck for speaking and teaching; Received salary from Glaxo for speaking and teaching; Partner received salary from Depuy for speaking and teaching.

Coauthor(s)

Kirk J Matthews, Jr, MD Resident Physician, Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Jori S Carter, MD, MS Gynecologic Oncologist, Women's Cancer and Wellness Institute

Jori S Carter, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American Society of Clinical Oncology, Association of Women Surgeons, International Society for Magnetic Resonance in Medicine, Society of Gynecologic Oncology

Disclosure: Nothing to disclose.

Chief Editor

Leslie M Randall, MD, MAS, FACS Professor and Director, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Diane Harris Wright Professor of Gynecologic Oncology Research, Massey Cancer Center, Virginia Commonwealth University School of Medicine

Leslie M Randall, MD, MAS, FACS is a member of the following medical societies: Academy for Innovation in Medical Education, American College of Surgeons, American Medical Association, American Society of Clinical Oncology, International Gynecologic Cancer Society, Society of Gynecologic Oncology

Disclosure: Nothing to disclose.

Acknowledgements

A David Barnes, MD, PhD, MPH, FACOG Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, California), Pioneer Valley Hospital (Salt Lake City, Utah), Warren General Hospital (Warren, Pennsylvania), and Mountain West Hospital (Tooele, Utah)

A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association