NEW YORK (360Dx) — Antibodies to human papillomavirus type 16 (HPV16) can be detected in the blood up to 28 years before diagnosis of throat cancer caused by the virus, indicating that they potentially could serve as a new biomarker for identifying people at high risk for the malignancy, according to a new study released today.
While throat cancer — or oropharyngeal squamous cell carcinoma (OPSCC) — can be caused by smoking and alcohol consumption, roughly 70 percent of cases in the US are attributable to HPV16 infection. It has been shown that antibodies against HPV16's cancer-causing E6 protein can be found in the blood of OPSCC patients, but the exact timing of seroconversion is unknown.
To better understand this issue, members of the international HPV Cancer Cohort Consortium measured HPV16-E6 antibodies in blood samples taken from 743 OPSCC patients before their cancer diagnosis — including 111 individuals who provided multiple samples — and 5,814 controls from North America, Europe, and Australia. The median time between first blood collection and diagnosis was about 11 years, with some patients providing samples as much as 40 years before their disease was detected.
The team found that HPV16-E6 antibodies could be detected in only in .4 percent of control group individuals, but in 26.2 percent of OPSCC patients. Notably, the antibodies were found in 27.2 percent of whi-te patients before their cancer diagnosis, but only in 7.7 percent of black patients. According to the study, which appears in the Annals of Oncology, this means that HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold in whites and 17.2-fold in blacks.
"This finding suggests that OPSCC is substantially more often driven by HPV16 in United States white patients than in black patients," the study's authors wrote. "Because HPV-related OPSCC generally has better survival than HPV-negative OPSCC, this observation may at least partly explain the survival disparity in OPSCC by race."
The investigators also found higher HPV16-E6 seroprevalence in people diagnosed in more recent calendar years — a finding that is consistent with the growing incidence of HPV16-linked throat cancer. Seroconversion was estimated to occur between six and 28 years before diagnosis, with the median age of seroconversion at 52 years. The median age of OPSCC diagnosis was 62 years.
Although the findings suggest that HPV16-E6 antibodies could be used to screen for people at increased risk of OPSCC, much work remains to be done, the researchers stated.
"Specifically, if an HPV16-E6 screening program were in place, one would expect screen-positive individuals to require years of continued evaluation before clinically actionable disease may occur, leading to potential psychosocial harms including anxiety," they wrote. Further, there are no evidence-based actionable interventions for those who screen positive, and translating the E6 biomarker will likely require identification and description of an as-of-yet identified oropharyngeal cancer precursor.
The authors also noted that their study was limited by the inherent heterogeneity between the participating cohorts. For example, most cases with long lead times came from a single cohort in Norway, making it difficult to determine whether the observed HPV16-E6 seroprevalence in the longer lead times is attributed to the lead time specifically, or to being in that cohort. "Unfortunately, there are few large cohort studies with both serial blood draws and very long follow-up, which are both required to understand HPV16-E6 seroconversion many years before OPSCC diagnosis," they wrote.
"Future studies will focus on the most appropriate way to follow up individuals who test positive for HPV16 antibodies and whether there is a way to identify premalignant lesions, as well as alternative ways of reducing the risk of eventually developing OPSCC," Mattias Johansson, a researcher at the International Agency for Research on Cancer in France and senior author of the study, said in a statement. "In other words, there is a long way to go before this biomarker can be used in clinical practice."