Risk of subsequent malignant neoplasms after an index potentially-human papillomavirus (HPV)-associated cancers

Cancer Epidemiol. 2020 Feb:64:101649. doi: 10.1016/j.canep.2019.101649. Epub 2019 Dec 6.


Background: Since the number of cancer survivors is increasing, it is imperative that we better understand the long-term consequences of these survivors. We assessed the risk of developing a second primary malignant neoplasm (SPMN) after an index potentially-HPV-associated cancers (P-HPV-AC).

Methods: We constructed a population-based cohort of patients with P-HPV-AC using Surveillance, Epidemiology, and End Results registry data (2000-2015). We limited patients to those with invasive P-HPV-AC [cervical, vagina, vulva, penile, anal, and oropharynx] based on the International Classification of Diseases for Oncology, 3rd edition. Excess SPMN risks were calculated based on standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR).

Results: A total of 105,644 patients with an index P-HPV-AC were identified, and 7.8 % developed a SPMN. In all P-HPV-AC patients, the overall SIR was 1.73 (95 % CI: 1.69-1.77) and EAR of 70.72 per 10,000 PYR. All index P-HPV-AC sites showed statistically significant increases in the risk of SPMN, except for anal cancer among men, compared with the general population. The greatest increase in risk of SPMN was observed among patients diagnosed with an index P-HPV-oropharyngeal cancer (SIR = 1.83; 95 % CI, 1.70-1.82 and SIR = 2.29; 95 % CI, 2.12-2.47 for men and women, respectively). Men developed SPMN mostly in aero-digestive tract whiles women developed SPMN both in aero-digestive tract and other HPV-associated cancer sites.

Conclusions: P-HPV-AC survivors experienced excess risk of SPMN. These findings have the potential to affect future surveillance practices and improve preventive healthcare for survivors of P-HPV-ACs.

Keywords: Cancer survivors; HPV-associated cancers; Human papillomavirus; Risk and burden; SEER; Second cancers; Second primary malignancies.

MeSH terms

  • Adolescent
  • Aged
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neoplasms / etiology*
  • Papillomaviridae / pathogenicity*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / virology
  • SEER Program