Michael G. Hudgens

Extended Human Papillomavirus Genotyping to Predict Progression to High-Grade Cervical Precancer: A Prospective Cohort Study in the Southeastern United States

Abstract Background: High-risk human papillomavirus (hrHPV) testing is utilized in primary cervical cancer screening, generally along with cytology, to triage abnormalities to colposcopy. Most screening-based hrHPV testing involves pooled detection of any hrHPV or of HPV16/18. Cervical neoplasia progression risks based on extended hrHPV genotyping—particularly non-16/18 hrHPV types—are not well characterized. HPV genotype-specific incidence of high-grade cervical intraepithelial neoplasia or more severe (CIN2+) following an abnormal screening result was examined. Methods: We assessed a US-based prospective, multiracial, clinical cohort of 343 colposcopy patients with normal histology (n = 226) or CIN1 (n = 117). Baseline cervical samples underwent HPV DNA genotyping, and participants were followed up to 5 years. Genotype-specific CIN2+ incidence rates (IR) were estimated with accelerated failure time models. Five-year CIN2+ risks were estimated nonparametrically for hierarchical hrHPV risk groups (HPV16; else HPV18/45; else HPV31/33/35/52/58; else HPV39/51/56/59/68). Results: At enrollment, median participant age was 30.1 years; most (63%) were hrHPV-positive. Over follow-up, 24 participants progressed to CIN2+ (7.0%). CIN2+ IR among hrHPV-positive participants was 3.4/1,000 person-months. CIN2+ IRs were highest for HPV16 (8.3), HPV33 (7.8), and HPV58 (4.9). Five-year CIN2+ risk was higher for HPV16 (0.34) compared with HPV18/45 (0.12), HPV31/33/35/52/58 (0.12), and HPV39/51/56/59/68 (0.16) (P = 0.05). Conclusions: Non-16/18 hrHPV types are associated with differential CIN2+ progression rates. HPV16, 33, and 58 exhibited the highest rates over 5 years. HPV risk groups warrant further investigation in diverse US populations. Impact: These novel data assessing extended HPV genotyping in a diverse clinical cohort can inform future directions to improve screening practices in the general population.

Cost-effectiveness of Human Papillomavirus Self-collection Intervention on Cervical Cancer Screening Uptake among Underscreened U.S. Persons with a Cervix

Abstract Background: We evaluate the cost-effectiveness of human papillomavirus (HPV) self-collection (followed by scheduling assistance for those who were HPV+ or inconclusive) compared with scheduling assistance only and usual care among underscreened persons with a cervix (PWAC). Methods: A decision tree analysis was used to estimate the incremental cost-effectiveness ratios (ICER), or the cost per additional PWAC screened, from the Medicaid/state and clinic perspectives. A hypothetical cohort represented 90,807 low-income, underscreened individuals. Costs and health outcomes were derived from the MyBodyMyTest-3 randomized trial except the usual care health outcomes were derived from literature. We performed probabilistic sensitivity analyses (PSA) to evaluate model uncertainty. Results: Screening uptake was highest in the self-collection alternative (n = 65,721), followed by the scheduling assistance alternative (n = 34,003) and usual care (n = 18,161). The self-collection alternative costs less and was more effective than the scheduling assistance alternative from the Medicaid/state perspective. Comparing the self-collection alternative with usual care, the ICERs were $284 per additional PWAC screened from the Medicaid/state perspective and $298 per additional PWAC screened from the clinic perspective. PSAs demonstrated that the self-collection alternative was cost-effective compared with usual care at a willingness-to-pay threshold of $300 per additional PWAC screened in 66% of simulations from the Medicaid/state perspective and 58% of simulations from the clinic perspective. Conclusions: Compared with usual care and scheduling assistance, mailing HPV self-collection kits to underscreened individuals appears to be cost-effective in increasing screening uptake. Impact: This is the first analysis to demonstrate the cost-effectiveness of mailed self-collection in the United States.