Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma

Cancer. 2001 Aug 15;92(4):805-13. doi: 10.1002/1097-0142(20010815)92:4<805::aid-cncr1386>;2-9.


Background: Epidemiologic evidence points to a connection between viral infection by the human papillomavirus (HPV) and a subgroup of squamous cell carcinoma of the oropharynx. To assess the impact of HPV infection on the response of these tumors toward radiotherapy, the authors retrospectively determined the presence of the virus and the integrity of the viral E2 gene in tumors of patients who have undergone curative irradiation.

Methods: Paraffin embedded biopsies from 99 patients were analyzed for HPV infection and E2 gene integrity by multiplex PCR. The experimental findings were correlated with clinical characteristics, known risk factors, and treatment outcome.

Results: Fourteen of 99 tumors were HPV positive (11 HPV16, 1 HPV33, 1 HPV35, and 1 HPV45). Human papillomavirus positivity was closely linked to female gender (odds ratio [OR], 5.75; P = 0.004), age older than 56 years (OR, 7.42; P = 0.012), nonsmokers (OR, 21.33; P = 0.00001), and alcohol abstainers (OR, 5.35; P = 0.012). There was an inverse association with p53 nuclear immunoreactivity (OR, 0.06; P = 0.008). The Kaplan-Meier survival estimates showed a better local control (P = 0.050, log-rank) and a better overall survival (P = 0.046, log-rank) for patients with HPV positive tumors. In the multivariate analysis, HPV positivity remained to be associated with a lower risk of local failure (risk ratio [RR], 0.31; P = 0.048). Four of 11 HPV16 positive tumors had a disrupted E2 gene. Only tumors with a disrupted E2 gene manifested local treatment failure.

Conclusions: Human papillomavirus positivity designates a specific subgroup of oropharyngeal squamous cell carcinomas of the oropharynx that arise preferentially among individuals with no consumption of tobacco and alcohol and that have a favorable outcome attributable to an increased sensitivity toward radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / virology*
  • Female
  • Genome, Viral
  • Humans
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / radiotherapy
  • Oropharyngeal Neoplasms / virology*
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / diagnosis*
  • Polymerase Chain Reaction
  • Proportional Hazards Models
  • Retrospective Studies
  • Survival Analysis
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Virus Infections / diagnosis*


  • Tumor Suppressor Protein p53