Etiologic Heterogeneity for Cervical Carcinoma by Histopathologic Type, Using Comparative Age-Period-Cohort Models

Abstract

Cervical carcinomas comprise two main histopathologic types, squamous cell carcinomas and adenocarcinomas. Human papillomavirus (HPV) infections are causative for both types but the respective tumors may have different carcinogenic pathways. To assess potential etiologic heterogeneity of cervical cancer by histopathologic type, we examined invasive squamous cell carcinomas and adenocarcinoma cervical cancer incidence rates in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. We complemented standard descriptive epidemiology with comparative age-period-cohort (APC) models fitted to each histopathologic type. Squamous cell tumors (n=25,219) were nearly 5-fold more common than adenocarcinomas (n=5,451). Age-adjusted incidence trends decreased for squamous cell carcinomas but increased for adenocarcinomas. Cross-sectional age-specific incidence rates increased more rapidly for squamous cell carcinomas than adenocarcinomas in adolescents and young adults then leveled off for both types. APC models confirmed that secular trends and age-specific rates differed for the two types (P=0 for the null hypothesis of no difference). For squamous cell carcinoma, the APC "fitted" age-at-onset rate curve peaked before age 40 years then declined; for adenocarcinoma, the fitted curve increased rapidly until age 40 years then rose more slowly. Despite the necessary role of HPV infection in both squamous cell carcinomas and adenocarcinomas of the cervix, secular trends and age-related natural histories differed for the two tumor types, consistent with etiologic heterogeneity. Future analytic and clinical studies should consider the interaction (effect modification) of HPV infection and other cervical carcinoma risk factors by histopathologic type, time, and age.