p16 Overexpression in Sinonasal Squamous Cell Carcinoma: Association with Human Papillomavirus and Prediction of Survival Outcomes

Author:

Hirakawa Hitoshi1,Ikegami Taro1ORCID,Touyama Masatomo1,Ooshiro Yurika1,Higa Tomoyo1,Higa Teruyuki1,Agena Shinya1,Kinjyo Hidetoshi1,Kondo Shunsuke1,Kise Norimoto1,Tanaka Katsunori1,Maeda Hiroyuki1,Tamaki Tomoko2,Wada Naoki2,Suzuki Mikio1ORCID

Affiliation:

1. Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan

2. Department of Pathology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan

Abstract

p16 overexpression is often used as a surrogate marker for human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma but remains an uncertain diagnostic tool for HPV-related sinonasal squamous cell carcinoma (SNSCC). Our study involved 79 consecutive SNSCC patients who were treated at a tertiary referral university hospital during 2006–2021. We retrospectively examined their clinical characteristics and conducted p16 immunohistochemistry and HPV detection. We found that 12.7% of the patients exhibited p16 overexpression, which was significantly more common in the nasal cavity and increased from 2015 onward. The HPV was a high-risk type and viral loads ranged from 4.2 to 1.6 × 106 copies/ng DNA with genome integration. Five-year overall survival (OS) and five-year relapse-free survival (RFS) rates were 74.6% and 69.9%, respectively. Our multivariate analysis showed that T category (T1–4a) and hemoglobin levels (≥13.7) were significant favorable prognostic factors for OS, while T category, performance status, and p16 overexpression were significantly associated with RFS. In patients with p16 overexpression, OS was 100% and RFS was 90%. Our findings suggest that p16 overexpression is a reliable surrogate marker for transcriptionally active HPV infection and predicts a favorable prognosis.

Funder

Grants-in-Aid for Scientific Research

Publisher

MDPI AG

Subject

General Medicine

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