Human papillomavirus genotype and prognosis of invasive cervical cancer: A nationwide cohort study.

Abstract

5525 Background: The role of human papillomavirus (HPV) in development from oncogenic infection to invasive cervical cancer (ICC) has been well established. However, the association of HPV genotypes and prognosis of ICC is controversial. Methods: We identified all ICC diagnosed in Sweden during the years 2002-2011 (4254 confirmed cases after clinical and histo-pathological review), requested all archival formalin-fixed, paraffin-embedded blocks and subjected them to comprehensive HPV genotyping. Twenty out of twenty-five archives agreed to the study, contributing a total of 2845 confirmed cases with valid HPV results. Cases were followed up from date of cancer diagnosis to 31 December, 2015, migration from Sweden, or death; whichever occurred first. Five-year relative survival ratios (RSRs) were calculated and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression. Results: HPV was detected in 2365 tumors (83.1% of all cases). The five-year RSR by tumor HPV status was 0.54 (HPV negative), 0.76 (HPV16 positive), 0.73 (HPV18 positive), 0.72 (other high-risk HPV positive) and 0.56 (low-risk HPV positive) compared to the age-matched general female population. Compared to cases with HPV-negative tumor, a significantly lower excess mortality was seen if the tumor was positive for HPV16 (EHR:0.54, 95% CI 0.44-0.65), other high-risk HPV (EHR:0.47, 95% CI 0.37-0.60), and low-risk HPV (EHR:0.48, 95% CI 0.32-0.74), after adjustment for age, time since cancer diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, educational level and histology. However, the mortality among women with HPV18 positive tumors were not statistically significantly different from cases with HPV-negative tumors. In women with a single HPV infection of either HPV16 or HPV18, those with HPV18-positive tumors had 56% (EHR:1.56, 95% CI: 1.13-1.97) higher excess mortality compared to women with HPV16-positive tumors. Conclusions: HPV genotype in cervical cancer tumor is associated with prognosis of ICC. Single HPV18 positivity indicated a poorer prognosis than single HPV16 positivity. This could add information of value beyond the established clinical prognostic factors for women diagnosed with ICC.