Evaluation of high-risk human papillomavirus in sinonasal papillomas and squamous cell carcinomas

Virchows Arch. 2023 Sep;483(3):381-392. doi: 10.1007/s00428-023-03601-x. Epub 2023 Jul 15.

Abstract

The sinonasal tract is considered a second hotspot for human papillomavirus (HPV)-related tumors in the head and neck, with HPV being identified in up to 62% of squamous cell carcinomas (SCCs) and 38% of papillomas. There is limited data from geographical regions with low prevalence of high-risk (HR)-HPV on the association of HR-HPV in sinonasal neoplasms and on utility of p16 as a surrogate marker. p16 immunohistochemistry, HR-HPV mRNA ISH and quantitative real-time PCR (qPCR) were performed on a retrospective cohort of sinonasal papillomas and SCCs. KRAS mutation analysis was done in oncocytic papillomas. p16 positivity was present in 22/142 cases (15.5%) including eight inverted papillomas, one oncocytic papilloma (OP), and 13 SCC. Among these, mRNA ISH showed HR-HPV in the OP and two SCC, while another SCC was found to harbour HPV18 by qPCR. Two HPV-associated SCCs had foci of OP. mRNA ISH was negative in all p16 negative cases. p16 immunohistochemistry showed 68% concordance with mRNA ISH, and had sensitivity and negative predictive value of 100%; specificity was 67%, and positive predictive value was 14.3%. Association with HR-HPV in sinonasal papillomas and SCC is rare, and may be seen in cases demonstrating oncocytic morphology. p16 immunohistochemistry has low specificity and positive predictive value in low-prevalence populations; thus, reflex direct HR-HPV testing should be performed in p16 immunopositive cases. This two-step approach is viable in resource-limited settings, as the proportion of p16 positive cases is small.

Keywords: Human papillomavirus; Oncocytic papilloma; Sinonasal carcinoma; Sinonasal papilloma; mRNA in situ hybridization; p16 immunohistochemistry.

MeSH terms

  • Carcinoma, Squamous Cell* / diagnosis
  • Carcinoma, Squamous Cell* / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Head and Neck Neoplasms*
  • Human Papillomavirus Viruses
  • Humans
  • In Situ Hybridization
  • Papilloma, Inverted* / pathology
  • Papillomaviridae / genetics
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / genetics
  • RNA, Messenger / genetics
  • Retrospective Studies

Substances

  • RNA, Messenger
  • Cyclin-Dependent Kinase Inhibitor p16