Correlation of transcriptionally active human papillomavirus status with the clinical and molecular profiles of head and neck squamous cell carcinomas

Head Neck. 2021 Jul;43(7):2032-2044. doi: 10.1002/hed.26676. Epub 2021 Mar 10.

Abstract

Background: To examine the molecular profiles of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinomas (HNSCCs), expression of epidermal growth factor receptor (EGFR), phospho-EGFR dimers, hypoxia markers, and cancer stem cell markers were evaluated.

Methods: HPV-status was confirmed using RNA-ISH. Immunohistochemical data of biomarker expression levels were analyzed using the Mann-Whitney U test. The clinical outcomes and biomarker expression in the HPV-positive (n = 25), matched HPV-negative (n = 49), and p16-positive/HPV-negative (n = 20) subgroups were comparatively analyzed.

Results: HPV was detected in 25 (5.8%) cases and was significantly associated with favorable outcomes. HPV-positive tumors exhibited lower membrane expression of EGFR, pEGFRY1068, pEGFRY1173, CD44, CD44v6, and CD98hc than HPV-negative and p16-positive tumors. The expression of HIF1α, CA9, ALDH1A1, and SOX2 was not significantly associated with HPV-status. The clinical outcomes and biomarker expression levels were similar between the HPV-negative and p16-positive HNSCC.

Conclusion: HPV-positive HNSCC exhibited distinct molecular profile compared to HPV-negative and p16-positive HNSCC. The clinical and molecular profiles were similar between p16-positive and HPV-negative subgroups.

Keywords: EGFR; HNSCC; cancer stem cell markers; human papillomavirus; hypoxia markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus*
  • Carcinoma, Squamous Cell* / genetics
  • Cyclin-Dependent Kinase Inhibitor p16
  • Head and Neck Neoplasms* / genetics
  • Humans
  • Papillomaviridae / genetics
  • Papillomavirus Infections*
  • Squamous Cell Carcinoma of Head and Neck / genetics

Substances

  • Cyclin-Dependent Kinase Inhibitor p16