HPV-16-E6 seropositivity is relatively common among people who later develop anal cancer, and less common but still more frequent than normal among people who later develop cervical, penile, vaginal, or vulvar cancer, according to a report published online Feb. 9 in Journal of Clinical Oncology.
Recent research has suggested that HPV-16 E6 seropositivity may indicate a higher risk of developing oropharyngeal cancers, and case-control studies have linked this HPV-16 protein to anogenital cancers as well. To explore this association, investigators analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which examined nutritional and lifestyle factors in more than 521,000 adults across 11 European countries in 1992-2000, said Aimée R. Kreimer, Ph.D., of the National Cancer Institute, Bethesda, Md, and her associates.
Using national cancer registries, Dr. Kreimer and her colleagues identified incident anogenital cancers that developed in study participants during the intervening decade. They then determined HPV-16 E6 seropositivity from blood samples drawn during the EPIC study for 273 patients with cervical cancer, 24 with anal cancer, 67 with vulvar cancer, 12 with vaginal cancer, and 24 with penile cancer, as well as for 718 matched but cancer-free controls. The median time between the blood draw and cancer diagnosis ranged between 7 and 8 years for all cancers except those of the cervix, for which the median lead time was only 3 years.
HPV-16 E6 seropositivity was relatively common only in the patients who developed anal cancer. It occurred in 7 of the 24 (29.2%), compared with only 4 of the control subjects (0.6%), for an odds ratio of 75.9. This means that the rate of anal cancer was 75 times higher among seropositive than seronegative participants. HPV-16 E6 seropositivity also was seen in 3.3% of patients with cervical cancer, 8.3% of those with penile cancer, 8.3% of those with vaginal cancer, and 1.5% of those with vulvar cancer, indicating a significantly elevated risk, but of a much smaller magnitude than found for anal cancer, the investigators said (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.57.8435]).
It is not yet clear why the strength of the associations between HPV-16 E6 and cancer differ by anatomic site, “but the immunobiology and proximity to the lymphatic system (and thus access to antigen-presenting cells) are likely important,” they said.
These results suggest that screening for anal cancer should be considered in the clinical work-up of people who test positive for HPV-16 E6. The main limitation of this study was that even using this large cohort, the number of cancers in every anatomic location except the cervix was quite small, “an inherent issue in studies of rare cancers,” the investigators added.