Risk estimation for the next generation of cervical cancer screening programs
Keywords: Risk modeling, Human Papillomavirus (HPV), pap smear, cervical biopsy, personalized medicine, medical decision making, comparative effectiveness research, HPV vaccine
Cervical cancer prevention based on human papillomavirus (HPV) testing and HPV vaccination is imminent. However, the challenge is to estimate the cost/benefit implications of different strategies for incorporating HPV testing and vaccines into current or new prevention programs. Cost-effective prevention programs must base criteria for intervention on a woman’s absolute risk for developing cervical precancer or cancer, but consensus absolute risk estimates are still lacking. In this talk, I describe the risk tool we are building to estimate absolute risk of cervical precancer or cancer for women based on cytological and virologic screening tests, vaccination, and other determinants of risk. Risk of cervical precancer is a unifying concept to guide clinical management, regardless of which combination of tests a woman has undergone, because risk of cervical precancer boils down a complex battery of test results over time into a single percentage that forms a basis for action. I will explain how our tool could help determine appropriate clinical action for women, and program-wide help determine optimal screening intervals and protocols. For example, if guidelines would handle all women with the same risk of cervical precancer in the subsequent 5 years the same, regardless of which tests provide this assessment, then management could be simplified greatly and applied consistently. Our risk tool has several advantages over current clinical algorithms, among them: (1) As new tests are introduced and as data accrue, risk estimates are readily updated once evidence of effectiveness for those new tests is solid. (2) Current algorithms obscure implicit assumptions about cancer risk; in contrast, the data behind risk estimates are available, with uncertainties presented in confidence intervals. Unlike all other cancers, cervical precancer is predictable with unprecedented accuracy and power because we can test for its necessary cause (HPV), a precancerous lesion has been defined, and we can readily access the cervix for screening and effective treatment. Cervical cancer prevention via risk estimation will be the paradigm for the rational, effective, and cost-effective way to prevent cancer.