Background: For the HPV-associated index cancer survivors, persistent HPV infection may remain a risk factor for preventable HPV-associated second primary cancer (HPV-SPC). However, the risk of HPV-SPCs among HPV-associated index cancer patients has not been well documented. Methods: Longitudinal data from 9 cancer registries of the Surveillance, Epidemiology, and End Results (SEER) database were used to identify cases of HPV-associated cancers diagnosed from 1973 to 2014. The HPV-SPC risk was quantified using standard incidence ratios (SIRs) and excess absolute risk (EAR) per 10,000 person-years at risk (PYR). Results: The SIRs for second primary HPV-related cancers after index HPV-related cancers among women and men were 3.3 (95% CI 3.2 to 3.4) and 15.8 (95% CI, 15.0 to 16.7), respectively; the EAR was 6.0 and 51.4 for women and men, respectively. When the same site second primary cancers were excluded, the risk remain significant both among women (SIR = 2.7) and men (SIR = 2.3). The risk of HPV-SPC was highest for oropharyngeal cancer both among women (SIR = 20.6; EAR = 83.8) and men (SIR = 18.8; EAR = 64.3), and lowest for cervical (SIR = 2.0; EAR = 2.4) and penile (SIR = 7.0; EAR = 20.7) cancer. Conclusions: The risk of developing HPV-SPC among HPV-related cancer survivors is significant, implying that HPV might be a cause for developing HPV-SPC. Our findings have the potential to inform surveillance recommendations among HPV-related cancer survivors.