Loss of p16 expression is a risk factor for recurrence in sinonasal inverted papilloma

Rhinology. 2022 Dec 1;60(6):453-461. doi: 10.4193/Rhin22.143.

Abstract

Background: The purpose of this study was to evaluate p16, p53, EGFR, pEGFR protein expression and HPV infection as possible markers of tumor progression in a series of sinonasal inverted papilloma (SNIP) and sinonasal squamous cell carcinoma (SNSCC).

Methods: A series of 49 SNIP, 11 SNSCC associated with SNIP (SNIP-SNSCC) and 52 SNSCC not associated with SNIP were analyzed for p16, p53, EGFR, and phosphorylated EGFR (pEGFR) expression by immunohistochemistry. Human papillomavirus (HPV) infection status was evaluated by DNA-PCR. Results were correlated to clinical and follow-up data.

Results: Reduced or loss of p16 expression was observed in 18% SNIP, 64% SNIP-SNSCC and 87% of SNSCC. Reduced or loss p16 staining in SNIP correlated with shorter recurrent SNIP-free follow-up. In contrast, p16 expression was not predictive of recurrent SNSCC in cases with SNIP-SNSCC and SNSCC. P53, EGFR, and pEGFR expression did not differ between the tumor groups, nor were they related to recurrent SNIP-free follow-up or recurrent SNSCC. Oncogenic HPV types 16 and 18 were detected in 5% of SNIP and 18% of SNIP-SNSCC, but not in SNSCC. There was no correlation between HPV infection and >70% p16 immunostaining.

Conclusions: HPV infection appears to play a minor role in SNIP and SNSCC and p16 immunostaining does not appear a valid surrogate marker for HPV. However, reduced or loss p16 expression may have prognostic value as a risk marker for recurrent SNIP.

MeSH terms

  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / virology
  • Cyclin-Dependent Kinase Inhibitor p16* / genetics
  • ErbB Receptors / metabolism
  • Humans
  • Neoplasm Recurrence, Local
  • Papilloma, Inverted* / genetics
  • Papilloma, Inverted* / virology
  • Papillomavirus Infections* / complications
  • Paranasal Sinus Neoplasms* / genetics
  • Paranasal Sinus Neoplasms* / virology
  • Risk Factors
  • Tumor Suppressor Protein p53

Substances

  • ErbB Receptors
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase Inhibitor p16
  • CDKN2A protein, human