Cervical cancer screening and prevention 2016

December 16, 2016

Expert commentary on Practice Bulletin No. 157: Cervical Cancer Screening and Prevention

COMMITTEE ON PRACTICE BULLETINS-Gynecology Practice Bulletin #157: Cervical Cancer Screening and Prevention (Replaces Practice Bulletin Number 131, November 2012). American College of Obstetricians and Gynecologists. Obstet Gynecol. 2016;127:e1–20. Full text of Practice Bulletin #168, an interim update of #157, is available to ACOG members at http://www.acog.org/Resources%20And%20Publications/Practice%20Bulletins/Committee%20on%20Practice%20Bulletins%20Gynecology/Cervical%20Cancer%20Screening%20and%20Prevention.aspx

Cervical Cancer Screening and Prevention
The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (1). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (2). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (3). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed (4, 5).New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk–benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (6), as did the U.S. Preventive Services Task Force (USPSTF) (7). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (8). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer.

Used with permission. Copyright the American College of Obstetricians and Gynecologists.


Cervical cancer screening and prevention 2016


By Ilana Cass, MD

Dr Cass is Vice Chair, Associate Clinical Professor, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California. She is also a member of the Contemporary OB/GYN editorial board.


Practice Bulletin #157, published in January 2016, replaces Practice Bulletin #131 from November 2012. (Practice Bulletin #168 [October 2016] is an interim update of #157.) Practice Bulletin #157 summarized the Bethesda 2014 Classification system for reporting cervical cytology and corresponding consensus management guidelines, expanded upon recent data regarding HPV testing, both as an adjunct to conventional cervical cytology and as primary cervical cancer screening alone, and compared efficacy of the 3 available HPV vaccines. Level A evidence provides support for lengthening screening intervals based upon the powerful negative predictive value of HPV testing and the natural history of HPV infection.
Practice Bulletin #157 reflects the ongoing efforts to balance the benefits and harms of cervical cancer screening to identify the optimal screening tools and intervals for women.

Screening evolution

The 2001 Bethesda system for reporting cervical cytology results and the seminal findings from the National Cancer Institute (NCI) ALTS trial for the triage of ASCUS and LSIL cytology paved the way for the creation of a standard management approach for women with abnormal cervical cytology. The American Society for Colposcopy and Cervical Pathology (ASCCP) developed evidence-based guidelines aligned with the Bethesda classification system to manage women with abnormal cervical cytology.1
In 2012, organizations including the American Cancer Society, the ASCCP, and the US Preventative Services Taskforce endorsed longer intervals between cervical cancer screening and delaying the onset of cervical cancer screening to age 21 for average-risk women. Cervical cancer screening further evolved with widespread adoption of co-testing as an alternative to cytology alone.2 A large clinical database at the Kaiser Permanente Medical Group Northern California provided evidence to guide management of abnormal cervical cancer screening tests including cytology and HPV co-testing.3,4 More than 900,000 women aged 30 to 64 were screened with co-testing between 2006 and 2010.
Analysis of data for 5-year CIN 3+ and cancer risks based upon HPV and cytology results are presented in the bulletin. The authors concluded that HPV status was a better predictor of CIN 3+ and cancer risk than cytology alone. Using the principle that women with similar risks of cervical neoplasia should be managed in similar ways, current consensus guidelines reflect estimated risks of CIN 3+ and cancer based upon patient age, cytology diagnosis, and HPV status, specifically infection with HPV-16 or 18.3,5 Co-testing in women over age 30 has led to the recommendation to further extend intervals between screening for low-risk women (HPV- and cytology-negative) and simplified surveillance for women who are HPV-positive but have normal cytology.


Primary HPV screening

Data from more recent studies have examined the role of HPV testing as a primary screen based upon the increased sensitivity and earlier detection of CIN 3+ compared to cervical cytology alone. Several countries including Australia and the Netherlands have adopted primary HPV screening to reduce the costs and complexities of co-testing.6 Concerns regarding poor specificity and uncertainty regarding triage of HPV-positive women, with potential overuse of diagnostic evaluation, has limited the adoption of primary HPV screening in the United States. In 2015, the ATHENA trial compared performance of primary HPV screening to cytology alone or co-testing in 42,209 women aged 25 or older. In the HPV primary screening strategy, HPV-negative women were re-screened in 3 years, HPV 16/18-positive women were triaged to colposcopy, and the presence of non-HPV16/18 oncogenic subtypes triggered reflex cytology with colposcopy for a cytology > ASCUS.

Among women aged 25 years or older, primary HPV screening detected more CIN 3+ than cytology or co-testing albeit with more colposcopies than co-testing, but a similar number of colposcopies per case of CIN 3+.6 One HPV test has been FDA-approved for women older than 25. Interim consensus guidelines from the Society of Gynecologic Oncologists, ASCCP, and other expert opinion advised that primary HPV screening using this approved platform may be considered an alternative to current cervical cancer screening strategies in women aged 25 years and older. Cytology alone and cotesting remain the options specifically recommended in current major society guidelines.
Further study is needed to optimize the detection of CIN 3+ among screen-detected HPV-positive women.7



HPV vaccination

Three HPV vaccines are available to prevent HPV infection. They target the most common oncogenic HPV subtypes including 6, 11, 16, and 18. The newest nonavalent vaccine protects against an additional 15% of cervical cancers attributed to 5 HPV subtypes: 31, 33, 45, 52, and 58, extending protection against 80% of all cervical cancer. To examine the public health impact of replacing the bi- or quadrivalent vaccine with the nonavalent (targeting 9 serotypes) vaccine, studies have modeled data based upon current HPV vaccination rates, sexual behavior, and cervical cancer progression. Switching to the nonavalent compared to the bi- or quadrivalent vaccine, if current vaccination rates in the United States were maintained, would decrease the incidence of cervical cancer by 73% versus 63%, respectively, and reduce cervical cancer-associated mortality by 49% versus 43%.8 The nonavalent vaccine is also cost-effective, resulting in the same health benefit, at current rates of vaccination, as covering an additional 11% of women with the bi- or quadrivalent vaccine with a projected savings of $2.7 billion.
Estimates indicate that 60% of girls in the United States start HPV vaccination but only half complete the series, resulting in a nationwide vaccination rate of approximately 33%.9 Parental obstacles to HPV vaccination include lack of information about the vaccine, perception that it is unnecessary, concern about side effects, and lack of doctor recommendation.10
Education coupled with the October 19, 2016 Advisory Committee on Immunization Practice recommendation to the CDC that only 2 HPV vaccinations, at least 6 months apart, confer adequate immunization for young adolescents (ages 9–14) may improve vaccination rates in the United States.11 Data from Victoria, Australia, which has achieved an 80% 3-dose HPV coverage rate through a nationally funded, school-based vaccination program, have demonstrated a decreased incidence of high-grade cervical lesions by 0.38% in girls younger than 18, proving that an ounce of prevention is worth a pound of cure.12

Abstract references

1. Howlader N, Noone AM, Krapcho M, et al, eds. SEER cancer statistics review, 1975-2012. Bethesda (MD): National Cancer Institute; 2015. Available at: http://seer.cancer.gov/csr/ 1975_2012.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5–29.
3. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available at: http://globocan.iarc.fr.
4. Gustafsson L, Ponten J, Bergstrom R, Adami HO. International incidence rates of invasive cervical cancer before cytological screening. Int J Cancer 1997;71:159–65.
5. Gustafsson L, Ponten J, Zack M, Adami HO. International incidence rates of invasive cervical cancer after introduction of cytological screening. Cancer Causes Control 1997;8:755–63.
6. 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. ACS-ASCCP-ASCP Cervical Cancer Guideline Committee. CA Cancer J Clin 2012;62:147–72.
7. Moyer VA. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. U.S. Preventive Services Task Force [erratum in Ann Intern Med 2013;158:852]. Ann Intern Med 2012;156:880–91, W312.
8. 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;125:330–7.

Commentary references

1. Wright TC, Cox JT, Massad LS, Twiggs LB, Wilkinston EJ. 2001 Consensus guidelines for the management women with cervical cytological abnormalities and cervical cancer precursors: Part 1. Cytological abnormalities. JAMA. 2002;287:2120-9.
2. 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;17:S1-27.
3. Katki HA, Schiffman M, Castle PE, et al. Five years of CIN 3+ and cervical cancer among women with HPV testing of ASCUS Pap results. J Low Genit Tract Dis. 2013;17:S36-42.
4. Katki HA, Schiffman M, Castle PE, et al. Five year risk of CIN 3+ and cancer for women who test Pap-negative, but are HPV-positive. J Low Genit Tract Dis. 2013;17:S56-63.
5. Sawaya GF. New guidelines. It’s complicated. Obstet Gynecol. 2013;121(4):703-4.
6. Wright TC, Stoler MH, Behrens CM, et al. 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;136:189-97.
7. Huh WK, Ault KA, Chemlow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim guidance. Obstet Gyecol. 2015;125:330-7.
8. Durham DP, Ndeffo-Mbah M, Skrip LA, et al.  National and state level impact and cost-effectiveness of nonavalent HPV vaccination in the United States. PNAS. 2016;113(18):5107-12.
9. CDC. HPV Vaccine Coverage Maps-Infographic. https://www.cdc.gov/hpv/infographics/vacc-coverage.html.
10. Holman DM, Benard V, Roland KB, Watson M, Liddon N, Stokley S. Barriers to human papillomavirus vaccination among US adolescents. A systematic review of the literature JAMA Peds. 2014;168(1):76-82.
11. CDC. CDC recommends only two HPV shots for younger adolescents. http://www.cdc.gov/media/releases/2016/p1020-hpv-shots.html.
12. Brotherton JL, Fridman M, May CL, et al. Early effect of the HPV vaccination program on cervical abnormalities in Victoria, Australia: an ecological study. Lancet. 2011;377:2085-2092.