HPV-Positive Oropharyngeal Carcinoma: A Systematic Review of Treatment and Prognosis

Otolaryngol Head Neck Surg. 2015 Nov;153(5):758-69. doi: 10.1177/0194599815592157. Epub 2015 Jun 29.


Objective: Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma is increasing in incidence and appears to exhibit improved response to treatment and better survival than that of HPV- head and neck squamous cell carcinoma. The purpose of this systematic review was to examine the current literature regarding treatment and prognosis of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) and identify whether type of treatment (primarily surgery vs primarily radiation) significantly affects survival rates.

Data sources: PubMed and Cochrane Library databases.

Review methods: A computerized search of the PubMed and Cochrane Library databases was performed to identify English-language articles published between January 1, 2000, and October 21, 2014. Studies were included only if they were prospective or retrospective observational series of OPSCC patients that reported HPV status, treatment regimen, and survival outcomes. Outcomes were determined for HPV+ and HPV- OPSCC patients, with subanalyses according to the type of treatment received.

Results: Fifty-six articles were eligible for this review. In the HPV+ analysis, the unadjusted hazard rate ratio (HR) for surgery vs radiation treatment was 1.33 (P = .114). Nine confounders were considered, and HRs were adjusted for each covariate. While HRs were almost all >1 for all covariates, none of the HRs was statistically significant at P < .05. The HR for HPV- OPSCC was higher for radiation than surgery.

Conclusions: HPV+ OPSCC has an improved prognosis and lower rates of adverse events when compared with HPV- OPSCC. HPV- OPSCC had significantly worse outcomes when treated with primary radiation as compared with primary surgery. There was no statistically significant difference in HRs for HPV+ OPSCC with primary radiation vs primary surgery treatment.

Keywords: HPV; head and neck cancer; human papillomavirus; oropharyngeal squamous cell carcinoma; p16; radiation; surgery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Carcinoma, Squamous Cell* / mortality
  • Carcinoma, Squamous Cell* / therapy
  • Carcinoma, Squamous Cell* / virology
  • Combined Modality Therapy
  • DNA, Viral / analysis*
  • Global Health
  • Humans
  • Oropharyngeal Neoplasms* / mortality
  • Oropharyngeal Neoplasms* / therapy
  • Oropharyngeal Neoplasms* / virology
  • Papillomaviridae / genetics*
  • Papillomavirus Infections* / mortality
  • Papillomavirus Infections* / therapy
  • Papillomavirus Infections* / virology
  • Prognosis
  • Registries*
  • Survival Rate / trends


  • DNA, Viral