title: A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening.
abstract: New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer/cancer using shared random-effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer/cancer. The model was fit to data on 9,553 HPV-positive/Pap-negative women undergoing cervical cancer screening at Kaiser Permanente Northern California, data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model to those from population-average marginal models of precancer/cancer risk. In particular, after 2 years the marginal population-average precancer/cancer risk was 5%, suggesting a 2-year interval to controlpopulation-averagerisk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to controlindividualrisk at 5%. The example suggests that sophisticated risk models capable of predicting individual risk may have different implications than population-average risk models that are currently used for informing medical guideline development.
authors.affiliation: Division of Cancer Epidemilogy and Genetics, US National Cancer Institute, NIH, Bethesda MD, USA.
authors.forename: Hormuzd A
authors.initials: HA
authors.lastname: Katki
authors.affiliation: Infomation Management Services, Inc., Calverton MD, USA.
authors.forename: Li C
authors.initials: LC
authors.lastname: Cheung
authors.affiliation: Kaiser Permanente Northern California, Berkeley CA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Fetterman
authors.affiliation: Albert Einstein College of Medicine, The Bronx NY, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.affiliation: Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville MD, USA.
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sundaram
keywords: HPV; cancer screening; joint modeling of longitudinal; medical guidelines; risk modeling; survival data