Discrepancy in p16 expression in patients with HPV-associated head and neck squamous cell carcinoma in Thailand: clinical characteristics and survival outcomes

BMC Cancer. 2021 May 6;21(1):504. doi: 10.1186/s12885-021-08213-9.

Abstract

Background: Lower prevalence HPV infection has been previously reported in Thai population when compared with Western countries. p16 expression indicates HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but not non-OPSCC. We therefore evaluated the characteristic and association of p16 and HPV in Thai patients with HNSCC.

Methods: We used immunohistochemistry and qPCR, respectively, to detect p16 and HPV DNA in archrival formalin-fixed paraffin-embedded HNSCC tissues. Patient characteristics and survival were analyzed.

Results: p16 expression was detected in tumors of 72 of 662 (10.9%) patients with HNSCC and was significantly associated with higher-grade histology, advanced nodal stage, and oropharynx. p16 was expressed in 28 and 6.5% of patients with OPSCC or non-OPSCC, respectively, and HPV DNA was detected in 15.6 and 1% of patients, respectively. Using p16 as a surrogate for HPV status, sensitivities were 80 and 25% in OPSCC and non-OPSCC, respectively. Positive and negative predictive rates of OPSCC were 38 and 95%. Discordance rates between HPV and p16 were 23 and 7% in OPSCC and non-OPSCC, respectively. Overall survival (OS) were significantly longer in both p16-positive OPSCC (p = 0.049), and non-OPSCC (p = 0.003).

Conclusions: Low prevalence of p16 and HPV associated OPSCC and non-OPSCC were confirmed in Thai patients. High discordance and low positive predictive rates of p16 were observed in HPV-associated OPSCC. p16 was a significant prognostic factor for OS for patients with OPSCC or non-OPSCC. Therefore, HPV testing should be performed to assess the association of HPV with HNSCC regardless of p16 expression.

Keywords: HPV; Head and neck squamous cell carcinoma; OPSCC; Oropharyngeal squamous cell carcinoma; p16.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alphapapillomavirus / isolation & purification*
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • DNA, Viral / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / chemistry*
  • Oropharyngeal Neoplasms / mortality
  • Oropharyngeal Neoplasms / virology
  • Papillomavirus Infections / complications*
  • Squamous Cell Carcinoma of Head and Neck / chemistry*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / virology
  • Young Adult

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral