Trade-offs in cervical cancer prevention: balancing benefits and risks

Abstract

Background: New screening and vaccination technologies will provide women with more options for cervical cancer prevention. Because the risk of cervical cancer diminishes with effective routine screening, women may wish to consider additional attributes, such as the likelihood of false-positive results and diagnostic procedures for mild abnormalities likely to resolve without intervention in their screening choices.

Methods: We used an empirically calibrated simulation model of cervical cancer in the United States to assess the benefits and potential risks associated with prevention strategies differing by primary screening test, triage test for abnormal results (cytologic testing, human papillomavirus [HPV] DNA test), and screening frequency. Outcomes included colposcopy referrals, cervical intraepithelial neoplasia (CIN) types 1 and 2 or 3, lifetime cancer risk, and quality-adjusted life expectancy.

Results: Across strategies, colposcopy referrals and diagnostic workups varied 3-fold, although diagnostic rates of CIN 2 or 3 were similar and 95% of positive screening test results were for mild abnormalities likely to resolve on their own. For a representative group of a thousand 20-year-old women undergoing triennial screening for 10 years, we expect 1038 colposcopy referrals (7 CIN 2 or 3 diagnoses) from combined cytologic and HPV DNA testing and fewer than 200 referrals (6-7 CIN 2 or 3 diagnoses) for strategies that use triage testing. Similarly, for a thousand 40-year-old women, combined cytologic and HPV DNA testing led to 489 referrals (9 CIN 2 or 3), whereas alternative strategies resulted in fewer than 150 referrals (7-8 CIN 2 or 3). Using cytologic testing followed by triage testing in younger women minimizes both diagnostic workups and positive HPV test results, whereas in older women diagnostic workups are minimized with HPV DNA testing followed by cytologic triage testing.

Conclusions: Clinically relevant information highlighting trade-offs among cervical cancer prevention strategies allows for inclusion of personal preferences into women's decision making about screening and provides additional dimensions to the construction of clinical guidelines.

Figure 1

Screening strategy A (conventional cytologic testing followed by additional cytologic testing for atypical squamous cells of undetermined significance [ASC-US]) and the follow-up actions subsequent to all possible test results. The strategy assumes standard guidelines for follow-up and management of abnormal results., ASC-H indicates atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesions (HSIL); CIN, cervical intraepithelial neoplasia; LSIL, low-grade squamous intraepithelial lesions.

Figure 2

Screening strategy B (liquid-based cytologic testing followed by human papillomavirus [HPV] triage testing for ASC-US) and the follow-up actions subsequent to all possible test results. The strategy assumes standard guidelines for follow-up and management of abnormal results., Other abbreviations are explained in the legend to Figure 1.

Figure 3

Screening strategy C (liquid-based cytologic testing and human papillomavirus [HPV] DNA testing in combination) and the follow-up actions subsequent to all possible test results. The strategy assumes standard guidelines for follow-up and management of abnormal results., Other abbreviations are explained in the legend to Figure 1.

Figure 4

Screening strategy D (human papillomavirus [HPV] DNA testing followed by cytologic triage testing) and the follow-up actions subsequent to all possible test results. The strategy assumes standard guidelines for follow-up and management of abnormal results., Other abbreviations are explained in the legend to Figure 1.

Figure 5

Expected screening outcomes and lifetime risk. Expected number of colposcopies and diagnoses of cervical intraepithelial neoplasia (CIN) types 1 and 2 or 3 among 1000 patients who undergo triennial screening for 10 years compared with the lifetime risk of invasive cervical cancer. On the left axis, the height of the bar shows the total number of colposcopies; the shaded portion is the number resulting in a diagnosis of CIN 1. The expected diagnoses of CIN 2 or 3, the solid black portion at the top of each bar, represent a small proportion of all colposcopic results (range, 6–7 for 20-year-old and 7–8 for 40-year-old women under all strategies). On the right axis, circles denote the lifetime risk of cervical cancer associated with each screening strategy. For comparison, current US screening patterns resulted in a lifetime risk of cervical cancer ranging from 0.47% to 0.69%. These results represent the population perspective but may be less useful for an individual woman because the outcomes are for a population of women participating in screening at different frequencies. HPV indicates human papillomavirus.