(Published June 2009)
Screening for HPV-Related Cancer: Cytology
Although human papillomavirus (HPV) is now known to play a role in a number of different cancers, national screening guidelines exist only for cervical cancer. This chapter will focus on the current methods used for cytology-based screening for cervical cancer, with brief mention of emerging recommendations on screening for anal cancer.
Screening for Cervical Cancer: Conventional versus Liquid-Based Cytology Methods
Both conventional Papanicolaou tests and liquid-based cytology are acceptable screening methods. Recent well-controlled clinical trials have found little difference in performance of the two methods for identifying high-grade disease.1-3 An advantage of the liquid-based cytology is that the technique facilitates “reflex” HPV testing, as well as testing for other sexually transmitted infections (STIs).
Age to Initiate Screening
If used, aggressive screening of young women would result in the evaluation of many minor cytological abnormalities because of the high prevalence HPV infection. This practice would be expensive, cause considerable anxiety, and result in unnecessary treatment. For this reason, the recommended age for initiation of cervical cancer screening is based on two opposing factors:
- HPV infections are very common in young women and frequently result in abnormal Pap test results.
- The incidence of CIN-3 and invasive cancer increases with age.
Within the United States, expert committees from American Cancer Society (ACS), American College of Obstetricians and Gynecologists (ACOG), and United States Preventive Services Task Force (USPSTF) recommend starting cervical cancer screening 3 years after initiation of sexual intercourse or no later than 21 years old.4-6
Age to Stop Screening
American Cancer Society guidelines specify that screening for cervical cancer can be stopped in women age 70 or older who have three documented, consecutive normal Pap test results within the preceding 10 years (with the exception of women with exposure to Diethylstilberstrol [DES], cervical cancer, or immunosuppression).4 In contrast, ACOG guidelines do not specify an age at which cervical cancer screening can be stopped, although they note that risk of cancer is low among older women who have adequate previous screening.5 USPSTF guidelines do not specify an age at which to stop screening but recommend against routine screening for women over age 65 who have had adequate recent screening and are not otherwise at high risk.6
The recommended frequency for cervical cancer screening varies by expert group but is in the range of every 2 to 3 years. ACS recommends annual screening if conventional Pap testing is used and screening every 2 years for liquid-based testing.4 The frequency of screening can be reduced to every 2 to 3 years at age 30 for women who have three normal consecutive Pap test results (unless there is a history of DES exposure or immunosuppression). Notice that recommendations on screening interval do not vary based on the number of sexual partners or other markers of sexual activity.
ACOG recommends annual screening for women who are less than 30 years old.5 The frequency of screening can be reduced to every 2 to 3 years at age 30 for women with three normal consecutive Pap tests (unless there is a history of DES exposure or immunosuppression). The ACOG guidelines also recommend that Pap testing with or without HPV testing can be used for screening for women age 30 or older. At age 30 if HPV and Pap test results are both negative, the screening interval can be changed to no more frequently than every 3 years.
The USPSTF guidelines state that cervical cancer screening should be conducted at least every 3 years.6 The guidelines note that there is no direct evidence to support the clinical utility of more frequent screening.
Screening After Hysterectomy
Recognizing that high-grade neoplasia is uncommon in women who have had a hysterectomy, ACS, ACOG, and USPSTF all recommend against routine screening of women who have had a hysterectomy for benign disease.4-7
Screening for Anal Cancer
Anal cancer is associated with infection with high-risk HPV types. As with cervical cancer, HPV type 16 is most common, followed by type 18.8 In fact, HPV DNA is detected in 88 percent to 94 percent of anal cancers.8 Risk factors for developing anal cancer include:9-10
- 15 or more lifetime sexual partners
- Receptive anal intercourse
- Current smoking
- In women, history of CIN, VIN, or VAIN
- HIV infection
Many anal cancers appear to arise from high-grade precursor lesions called anal intraepithelial neoplasia (AIN). The prevalence of anal HPV infections and AIN is quite high in certain populations including men who have sex with men (MSM) and HIV-infected individuals. In one study, 95 percent of 357 gay males had anal HPV and 50 percent had high-grade AIN.11 The role of routine screening for AIN and anal cancer in high-risk individuals is controversial.
Advocates for screening believe that cytology is as effective for detecting anal disease as it is for cervical disease, but opponents point out that treatments for AIN often fail and there are no data suggesting that AIN treatment prevents cancer.12 Currently, national expert groups, including the Centers for Disease Control and Prevention, USPSTF, ACS, and the Infectious Diseases Society of America, do NOT recommend routine anal cytology screening. Similarly, the National Guidelines Clearinghouse maintains no guidelines for anal cytology screening. However, some local entities, such as the New York State Department of Health, recommend anal cytology for certain populations (in this case, HIV-infected individuals who are MSM, individuals who have had genital warts, or women who have had CIN or VIN).13
- Davey E, Barratt A, Irwig L, Chan SF, Macaskill P, Mannes P, et al. Effect of study design and quality on unsatisfactory rates, cytology classifications, and accuracy in liquid-based versus conventional cervical cytology: a systematic review. Lancet. 2006;367(9505):122-32.
- Ronco G, Segnan N, Giorgi-Rossi P, Zappa M, Casadei CP, Carozzi F, et al. Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial. J Natl Cancer Inst. 2006;98(11):765-74.
- Taylor S, Kuhn L, Dupree W, Denny L, De Souza M, Wright TC, Jr. Direct comparison of liquid-based and conventional cytology in a South African screening trial. Int J Cancer. 2006;118(4):957-62.
- Saslow D, Runowicz CD , Solomon D, Moscicki AB, Smith RA, Eyre HJ, et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin. 2002;52;342-62.
- ACOG Committee on Practice Bulletins. ACOG Practice Bulletin: clinical management guidelines for obstetrician-gynecologists. Number 45, August 2003. Cervical cytology screening (replaces committee opinion 152, March 1995). Obstet Gynecol. 2003;102(2):417-27.
- United States Preventive Services Task Force. Screening for Cervical Cancer: Recommendations and Rationale. Rockville, MD: Agency for Healthcare Research and Quality. Publ. No. 03-515A. 2003.
- Pearce KF, Haefner HK, Sarwar SF, Nolan TE. Cytopathological findings on vaginal Papanicolaou smears after hysterectomy for benign gynecologic disease. N Engl J Med. 1996;335(21):1559-62.
- Munoz N, Castellsague X, de Gonzalez AB, Gissmann L. HPV in the etiology of human cancer. Vaccine. 2006; 24 (Suppl 3):S3/1-S3/10.
- Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA, et al. Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer. 2004;101(2):270-80.
- Frisch M, Smith E, Grulich A, Johansen C. Cancer in a population-based cohort of men and women in registered homosexual partnerships. Am J Epidemiol. 2003;157(11):966-72.
- Palefsky JM, Holly EA, Efirdc JT, Da Costa M, Jay N, Berry JM, et al. Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men. AIDS. 2005;19(13):1407-14.
- Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among HIV-infected persons—2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep. 2002;51(RR-8):1-52.
- New York State Department of Health AIDS Institute. Neoplastic complications of HIV disease. Available at: www.hivguidelines.org. Accessed September 24, 2007.