Purpose: Current guidelines for cervical cancer screening provide women with a range of strategies deemed equally acceptable in reducing cancer risk. As this risk becomes small, other attributes, such as the likelihood of false positive results and risk of referral for diagnostic procedures, may become more salient to women's decision making. We assess the benefits and potential harms associated with cervical cancer screening policies involving cytology and HPV testing, and in the context of an HPV 16,18 vaccine.

Methods: We use a Monte-Carlo computer model of the natural history of cervical cancer to simulate alternative cervical cancer prevention strategies in a representative cohort of U.S. women. The model was empirically-calibrated to epidemiologic data and validated against independent U.S. data. Prevention policies differ by primary screening test, triage test for abnormal results (cytology, HPV DNA), screening frequency, and HPV vaccination. Outcomes include false positive results, colposcopy referrals, cervical intraepithelial neoplasia (CIN 1 and 2,3), lifetime cancer risk, life expectancy, and quality-adjusted life expectancy.

Results: Across strategies, the colposcopy referrals a woman may expect from ten years of screening differ three- to five-fold, although CIN 2,3 diagnoses are similar. Over 95% of tests referred for additional diagnostic workup are in women with no abnormality or with CIN 1 likely to regress. Excessive referrals are highest with combination HPV testing/cytology and lowest with HPV/cytology triage, although the latter has a greater likelihood of an initially positive test than screening with cytology. Restricting HPV/cytology triage to women over age 30 minimizes the referral rate and likelihood of HPV positive results. While vaccination reduced referral rates overall, a greater proportion of referrals are considered “excessive” as the risk for cancer is lower.

Conclusions: As the risk of cervical cancer becomes small, with more sensitive HPV diagnostics and HPV 16,18 vaccination, women may wish to consider their screening choices in the context of other attributes such as the potential for anxiety associated with positive test results and diagnostic workup protocols that can last several months. Our results provide an initial step toward a comprehensive set of clinically relevant information highlighting these tradeoffs between screening policies to ultimately better inform women's decisions, as well as provide additional dimensions to the construction of clinical guidelines.