Approximately one-third of cases of oropharyngeal cancer carried antibodies to one of the driver proteins from HPV16, and those antibodies could be detected more than 10 years prior to the diagnosis of the cancer.
Ruth C. Travis
Approximately one-third of cases of oropharyngeal cancer carried antibodies to one of the driver proteins from human papillomavirus type 16 (HPV16), and those antibodies could be detected more than 10 years prior to the diagnosis of the cancer.
The findings were published in the Journal of Clinical Oncology.
Almost all cases of cervical cancer can be linked to HPV16, but the link between that specific strain of the virus and head and neck cancer is less clear. However, the virus has been associated with a rapid increase in the incidence of oropharynx cancer in many places around the world—including the United States where it has been linked to more than 50% of cases.
To draw a clearer association between the virus and oropharynx cancer, researchers focused on antibodies against HPV oncogene 6. The protein E6 from the HPV16 virus disables p53 and its ability to prevent DNA damage and the development of cancer.
In this study, 638 patients with head and neck cancers (including 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers were compared with 1599 control patients, with all patient data coming from the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples were collected from patients at an average of 6 years prior to diagnosis. These samples were analyzed for antibodies against multiple HPV16 proteins as well as other strains of the virus.
The researchers found that HPV16 E6 seropositivity was present in prediagnostic samples in 34.8% of patients with oropharyngeal cancer compared with 0.6% of controls (odds ratio [OR] = 274; 95% CI, 110-681). However, this seropositivity was not associated with any of the other cancer types in this study. An increased risk of oropharyngeal cancer among those with E6 seropositivity was independent of time between blood collection and diagnosis. Furthermore, this seropositivity was observed more than 10 years before diagnosis. Compared with seronegative patients, the all-cause mortality among patients with oropharyngeal cancer who were HPV16 E6 seropositive was 0.30 (95% CI, 0.13-0.67).
“These striking results provide some evidence that HPV16 infection may be a significant cause of oropharyngeal cancer,” said Ruth C. Travis, a postdoctoral research scientist at Cancer Research UK and the University of Oxford and one of the coauthors of the study, in a statement.
The link between HPV16 and oropharyngeal cancer might signal an increased incidence, but cases of the cancer with this specific strain of the virus were associated with better outcomes. The researchers found that the 5-year survival for patients who were seropositive was 84% compared with 58% of patients who were seronegative.
Two vaccines (Gardasil and Cervarix) have been approved by the FDA for the prevention of some cancers caused by HPV, including cervical, vulvar, and vaginal cancers, but more research is needed to determine its effectiveness in other tumor types. “If the HPV vaccine can also prevent against oral HPV infections and cancers, then it could have a broader potential effect,” noted Sara Hiom, a spokesperson for Cancer Research UK.
Kraimer AR, Johansson M, Waterboer T, et al. Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. J Clin Oncol. 2013;31(21):2708-2715.