HPV Screening and Follow-Up Protocol

Universal HPV screening is the goal, regardless of screening method


By Salina Zhang and Pelin Batur, MD


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Is there a best screening protocol?

The USPSTF reviewed large randomized and observational studies to summarize the effectiveness of the three screening strategies and commissioned a decision analysis model to compare the risks, benefits and costs of the three screening algorithms. The guideline statement notes both cotesting and high-risk HPV testing offer similar cancer detection rates: each prevents one additional cancer per 1,000 women screened as opposed to Pap-only testing.19

Also, tests that incorporate high-risk HPV screening may offer better detection of cervical adenocarcinoma (which has a worse prognosis than the more common squamous cell carcinoma type). However, both HPV-based screening strategies are more likely to require additional colposcopies for follow-up than Pap-only screening (1,630 colposcopies required for each cancer prevented with high-risk HPV alone, 1,635 with cotesting). Colposcopy is a simple office procedure that causes minimal discomfort to the patient.

The USPSTF guideline also differs in the recommended frequency of high-risk HPV-only testing; a high-risk HPV result should be repeated every five years if normal (as opposed to every three years as recommended by ACOG and ASCCP).19 The five-year recommendation is based on analysis modeling, which suggests that performing high-risk HPV-only testing more frequently is unlikely to improve detection rates but will increase the number of screening tests and colposcopies.19

No trial has directly compared cotesting with high-risk HPV testing for more than two rounds of screening. The updated USPSTF recommendations are based on modeling estimates and expert opinion, which assesses cost and benefit vs harm in the long term. Also, no high-risk HPV test is currently FDA-approved for every-five-year screening when used by itself.

All three cervical cancer screening methods provide highly effective cancer prevention, so it is important for providers to choose the strategy that best fits their practice. The most critical aspect of screening is getting all women screened, no matter which method is used.


It is critical to remember that the screening intervals are intended for patients without symptoms. Those who have new concerns such as bleeding should have a diagnostic Pap done to evaluate their symptoms.

Follow-up of abnormal results

Regardless of the pathway chosen, appropriate follow-up of any abnormal test result is critical to the early detection of cancer. Established follow-up guidelines exist,22,23 but accessing this information can be difficult for the busy clinician. The ASCCP has a mobile phone application that outlines the action steps corresponding to the patient’s age and results of any combination of Pap or HPV testing. The app also includes the best screening algorithms for a particular patient.24

All guidelines agree that cervical cancer screening should start at age 21, regardless of HPV vaccination status or age of sexual initiation.17,18,25 Screening can be discontinued at age 65 for women with normal screening results in the prior decade (three consecutive negative Pap results or two consecutive negative cotest results).23

For women who have had a total hysterectomy and no history of cervical neoplasia, screening should be stopped immediately after the procedure. However, several high-risk groups of women will need continued screening past the age of 65, or after a hysterectomy.

For a woman with a history of stage two cervical intraepithelial neoplasia or higher grade lesions, routine screening is continued for an additional 20 years, even if she is over age 65. Pap-only testing every three years is acceptable, because the role of HPV testing is unclear after hysterectomy.23 Prior guidelines suggested annual screening in these patients, so the change to every three years is notable. Many gynecologic oncologists will recommend that women with a history of cervical cancer continue annual screening indefinitely.


Within the first two to three years after treatment for high-grade dysplastic changes, annual follow-up is done by the gynecologic oncology team. Providers who offer follow-up during this time frame should keep in communication with the oncology team to ensure appropriate, individualized care. These recommendations are based on expert opinion, so variations in clinical practice may be seen.

Women infected with the human immunodeficiency virus can have Pap-only testing every three years, after a series of three normal annual Pap results.26 But screening does not stop at age 65.23,26 For patients who are immunosuppressed or have a history of diethylstilbestrol exposure, screening should be done annually indefinitely.23


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  3. American Cancer Society. Key statistics for cervical cancer. www.cancer.org/cancer/cervical-cancer/about/key-statistics.html. Accessed February 14, 2019.
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  12. Reagan-Steiner S, Yankey D, Jeyarajah J, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(33):850-858. doi:10.15585/mmwr.mm6533a4
  13. Gilkey MB, Calo WA, Moss JL, Shah PD, Marciniak MW, Brewer NT. Provider communication and HPV vaccination: The impact of recommendation quality. Vaccine. 2016;34(9):1187-1192. doi:10.1016/j.vaccine.2016.01.023
  14. Brewer NT, Hall ME, Malo TL, Gilkey MB, Quinn B, Lathren C. Announcements versus conversations to improve HPV vaccination coverage: a randomized trial. Pediatrics. 2017;139(1):e20161764. doi:10.1542/peds.2016-1764
  15. American Cancer Society. HPV vaccine facts. www.cancer.org/cancer/cancer-causes/infectious-agents/hpv/hpv-vaccine-facts-and-fears.html. Accessed February 14, 2019.
  16. National Cancer Institute; Chasan R, Manrow R. Cervical cancer. https://report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid=76. Accessed February 14, 2019.
  17. The American College of Obstetricians and Gynecologists (ACOG). Frequently asked questions. Cervical cancer screening. www.acog.org/Patients/FAQs/Cervical-Cancer-Screening. Accessed February 14, 2019.
  18. Saslow D, Solomon D, Lawson HW, et al; American Cancer Society; American Society for Colposcopy and Cervical Pathology; American Society for Clinical Pathology. 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. Am J Clin Pathol. 2012;137(4):516-542. doi:10.1309/AJCPTGD94EVRSJCG
  19. US Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(7):674–686. doi:10.1001/jama.2018.10897
  20. Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015;136(2):189-197. doi:10.1016/j.ygyno.2014.11.076
  21. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstet Gynecol. 2015;125(2):330-337. doi:10.1097/AOG.0000000000000669
  22. Massad LS, Einstein MH, Huh WK, et al; 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):829-846. doi:10.1097/AOG.0b013e3182883a34
  23. Committee on Practice Bulletins—Gynecology. Practice Bulletin No. 168: cervical cancer screening and prevention. Obstet Gynecol. 2016;128(4):e111-e130. doi:10.1097/AOG.0000000000001708
  24. ASCCP. Mobile app. http://www.asccp.org/store-detail2/asccp-mobile-app. Accessed February 14, 2019.
  25. USPSTF. Draft recommendation: cervical cancer: screening. www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/cervical-cancer-screening2. Accessed February 14, 2019.
  26. Masur H, Brooks JT, Benson CA, Holmes KK, Pau AK, Kaplan JE; National Institutes of Health; Centers for Disease Control and Prevention; HIV Medicine Association of the Infectious Diseases Society of America. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58(9):1308-1311. doi:10.1093/cid/ciu094

Note: This article was originally published in the Cleveland Clinic Journal of Medicine.

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