Effect of HPV on head and neck cancer patient survival, by region and tumor site: A comparison of 1362 cases across three continents

Oral Oncol. 2016 Nov:62:20-27. doi: 10.1016/j.oraloncology.2016.09.005. Epub 2016 Sep 26.

Abstract

Objectives: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers.

Methods: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S. (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally tested for p16INK4a and HPV16 DNA (by PCR). Risk of mortality was examined using Cox proportional hazard models.

Results: There were 517 OPSCC and 845 non-OP HNSCC. Cases were primarily male (81%), ever smokers (91%), with median age of 58yearsandmedian follow-up of 3.1years (IQR=1.4-5.9). Among OPSCC, the risk of mortality was significantly lower among 184 HPV-related (i.e., p16+/HPV16+) compared to 333 HPV-unrelated (p16- and/or HPV16-) cases (HR=0.25, 95%CI=0.18-0.34). Mortality was reduced among HPV-related OPSCC cases from the U.S., Europe, and Brazil (each p⩽0.01) and after adjustment, remained significantly reduced (aHR=0.34, 95%CI=0.24-0.49). Among non-OP HNSCC, neither p16 (aHR=0.83, 95%CI=0.60-1.14), HPV16 DNA (aHR=1.20, 95%CI=0.89-1.63), or p16+/HPV16+ (aHR=0.59, 95%CI=0.32-1.08) was a significantly predictor of mortality. When interaction was tested, the effect of HPV16/p16 was significantly different in OPSCC than non-OP HNSCC (p-interaction=0.02).

Conclusion: HPV-related OPSCCs had similar survival benefits across these three regions. Prognostic utility of HPV among non-OP HNSCC is limited so tumor HPV/p16 testing should not be routinely done among non-OP HNSCC.

Keywords: Brazil; Europe; HNSCC; HPV; Non-OP; Oral HPV; P16; Prognostic; Risk factors; Survival.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Alphapapillomavirus / isolation & purification*
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / virology*
  • Female
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / virology*
  • Humans
  • Male
  • Middle Aged
  • Squamous Cell Carcinoma of Head and Neck
  • Survival Analysis