Incidence and Risk Factors of Second Primary Cancer after the Initial Primary Human Papillomavirus Related Neoplasms

Background Human papillomavirus (HPV)-related cancers are nowadays associated with better survival. However, comprehensive studies in second primary cancer (SPC) after the initial primary HPV-related cancer still remain warranted. Therefore, this study was designed to analyse the incidence and risk factors of SPC after HPV-related cancer. Methods We identified 86,790 patients diagnosed with initial primary HPV-related cancer between 1973 and 2010 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) 9 database. Standardized incidence ratio (SIR) and cumulative incidence were calculated to assess the risk of SPC after HPV-related cancer. Subdistribution hazard regression was also conducted to figure out the risk factors. Results SIR of SPC after HPV-related cancer was 1.60 (95% confidence interval [CI] 1.55-1.65) for male and 1.25 (95% CI 1.22-1.28) for female. SIR of second primary HPV-related cancer (7.39 [95% CI 6.26-8.68] male and 4.35 [95% CI 4.04-4.67] female) was obviously higher than that of second primary HPV-unrelated cancer (1.54 [95% CI 1.49-1.60] male and 1.16 [95% CI 1.13-1.19] female). 5-year cumulative incidence of SPC was 7.22% (95% CI 6.89%-7.55%) for male and 3.72% (95% CI 3.58%-3.88%) for female. Risk factors of SPC included being married and initial primary cancer (IPC) diagnosed at earlier stage for both gender, and IPC diagnosed at older age as well as surgery performed for female only. Conclusion Patients diagnosed with HPV-related cancer are more likely to develop another primary cancer, as compared with the age-specific reference population. Patients with the risk factors claimed in this study are suggested to screen for SPC regularly. According to the elevation of SIR of HPV-related SPC, it is suggested that part of the HPV-related SPC cases may be caused by the persistent infection of HPV.