Background: Approximately 39,000 HPV-associated cancers are diagnosed annually in the US. Oncogenic HPV-infections are associated with virtually all cases of cervical, 95% of anal, 73% of oropharyngeal, 65% of vaginal, 50% of vulvar, and 35% of penile cancers. Cancer survivors are at increased risk of a second primary malignancy (SPM). We assessed the risk of developing a SPM after an index potentially-HPV-associated cancer (P-HPV-AC). Methods: This was population-based cohort study of patients with P-HPV-AC in the Surveillance, Epidemiology, and End Results registry (2000-2014). Only patients with invasive P-HPV-AC [cervical, vagina, vulva, penile, anal canal, and oropharynx] per International Classification of Diseases for Oncology, 3^rd edition, were included. SPM was defined as the first subsequent primary cancer occurring at least 2 months after first cancer diagnosis. Excess SPM risk was quantified using standardized incidence ratios (SIRs) stratify by gender. Results: A total of 100,960 patients with an index P-HPV-AC were identified, and 7.37% developed a SPM overall. In all P-HPV-AC patients, the overall SIR was 1.72 (95% CI: 1.68–1.76). All index P-HPV-AC sites presented with a statistically significant increase in the risk of SPM. Among males, the greatest increase in risk of SPM was observed among patients diagnosed with an index P-HPV-AC oropharynx (SIR = 1.83; 95% CI, 1.76–1.90). Among females, the greatest increase in risk of SPM was observed among patients diagnosed with an index P-HPV-AC oropharynx (SIR = 2.47; 95% CI, 2.29–2.65, Table). Conclusions: HPV cancer survivors experience significantly excess risk of SPM; thereby calling for a more effective program for surveillance of patients with HPV-associated cancers.