To aid decision making by women and their primary care physicians, we enumerated health-related benefits and potential harms for 4 main screening strategies using cytologic and HPV DNA testing. These strategies pose tradeoffs between minimizing cancer risk (already small with regular screening) and minimizing the risk of false-positive test results and excessive diagnostic procedures. Because women vary in the relative values they place on these trade-offs, providing comparative information for women and their physicians may help them choose among several screening strategies. Although no strategy will eliminate false-positive results and excessive colposcopy referrals, the risk is greater for some strategies than for others.
Although differences in a woman’s lifetime cancer risk associated with alternative screening approaches are small, the difference in colposcopy referrals is 3-fold. Combined screening with 2 tests, cytologic testing and HPV DNA testing, leads to the highest number of false-positive results and excessive referrals across all screening frequencies, even when restricted to women older than 30 years. Although the sensitivity of combined cytologic and HPV testing is highest, expected CIN 2 or 3 diagnoses are similar for all 4 strategies. Combined cytologic and HPV testing also resulted in high numbers of CIN 1 diagnoses. For younger women, nearly half of all colposcopies resulted in a CIN 1 diagnosis regardless of strategy. Because most CIN 1 is likely to regress, this potential overdiagnosis may also be of particular concern, especially if conservative management guidelines are not followed and overtreatment occurs and/or if a woman’s quality of life is compromised by the need for repeated visits and more frequent follow-up screening.
For women who experience short-term anxiety around screening and diagnostic workup, quality of life could be an important criterion for decision making if several screening options associated with similar cancer risk reduction are available. Although HPV testing followed by cytologic triage testing is less likely to result in a colposcopy referral than cytologic testing followed by HPV triage testing, there is a greater likelihood of an initially positive screening test result, especially in younger women, reflecting the significant prevalence of high-risk HPV infection in the second and third decades of life. Using cytologic test–based strategies in younger women minimizes the rate of both excessive diagnostic workups and HPV positive results on the initial screening test. This finding may be particularly important for women who experience additional disutility from the diagnosis of a sexually transmitted disease compared with an abnormal cytologic test result.
We purposefully focused on clinical outcomes and did not consider costs in this analysis. Cost-effectiveness analyses, which include the strategies examined herein, have been conducted with the goal of ascertaining comparative “value for resources” at a population level.14
Our objective is different. Women are generally faced with multiple options deemed acceptable in clinical guidelines and may in fact make choices that differ from those strategies found to be most cost-effective.24
We sought to provide comparative information on a broader range of attributes to allow women and their primary care physicians to select a screening approach reflective of individual preferences (). To make our results most useful in a real-world context, which includes decision makers who consider cost-effectiveness an important criterion or those developing prevention guidelines, we selected strategies that reflect current US practice and recommendations, have been found to be cost-effective, and/or are being evaluated in clinical studies.
Despite our focus on the individual, this analysis has implications at the population level. It has been estimated that 65 million cytologic screening tests are performed in the United States annually.27
Considering the United States as a whole, our analysis shows that, if all women 18 to 70 years old were screened triennially using cytologic testing followed by HPV triage testing per current guidelines, more than 1 million excessive colposcopies would be performed annually. For a strategy of HPV testing followed by cytologic triage testing, 0.7 million excessive colposcopies would be expected; in sharp contrast, with a strategy of combined cytologic and HPV testing, this figure increased to 4 million. Nearly 1.5 million of these excessive diagnostic procedures could be eliminated by substituting a cytologic test–based strategy for women younger than 30 years, emphasizing why the combination strategy is not part of the recommended screening guidelines for this age group. Even for women older than 30 years, combined use of cytologic and HPV testing is associated with nearly 3 times more excessive colposcopies compared with cytologic test–based strategies and more than 5 times more than HPV followed by cytologic triage testing. Because the implications for resource utilization could be substantial, this information might be useful to other decision makers, such as health care organizations responsible for providing care to their insured populations.
For our analysis we used a modeling approach and, as such, formidable limitations are related to the data and assumptions necessary for the model. The natural history of HPV infection and cervical cancer is unobservable. As with any model, unobservable variables were constrained by structural assumptions and fit to epidemiologic data. Our model is biologically plausible and produces results consistent with observational data.15
To establish an upper bound on both the risks and benefits achievable, we assumed 100% adherence to the screening protocol for each strategy. One can infer by the results for other screening frequencies what outcomes would be if women participated less regularly. Finally, we did not address qualitative aspects that affect women’s decision making regarding screening participation (eg, preferences for screening frequency, presentation of numerical results, or peace of mind from diagnostic resolution).
The newly available HPV 16 and 18 vaccine will pose additional challenges to the evaluation of screening policies. If long-term performance of the HPV vaccines is as promising as the short-term performance,7,8
the marginal health benefit from screening will be even smaller, potentially accentuating trade-offs in risks among strategies for some women. Although the effect of widespread use of the vaccine on HPV infection dynamics is as yet unknown and will not be known for several years, the relative performance of cytologic and HPV DNA testing will likely be affected.28
Undoubtedly, in vaccinated women, the ratio of false-positive to true-positive screening test results will increase if screening strategies remain the same. Although we chose to focus on providing information to women making decisions about screening today, these issues will be critical to explore in terms of both empirical data analysis and cost-effectiveness analysis.
There is great promise in the availability of accurate HPV diagnostics, new screening technology, and HPV vaccination for successful cervical cancer prevention in the United States. From both an individual and population perspective, the range of new options for prevention will ideally be assembled in such a way as to improve cancer outcomes, reduce disparities, and minimize the risk of overdetection of abnormalities likely to resolve on their own. As the risk of cervical cancer becomes small, in part owing to an already successful secondary prevention program and the availability of new technologies, women and their primary care physicians may wish to consider their choices in the context of a more fully descriptive range of screening strategy attributes. Existing information, however, about cervical cancer prevention directed toward the lay public has not always presented the benefits and risks from screening in a manner that illustrates all potential consequences.29
We sought to provide insight into the trade-offs associated with a range of cervical cancer screening policies. These results provide an initial step toward a comprehensive set of clinically relevant information highlighting trade-offs among screening policies to ultimately better inform women’s decisions and provide additional dimensions for the construction of clinical guidelines.