Possible Marker for Recurring HPV Linked Oropharyngeal Cancers

        A look-back analysis of HPV infection antibodies in patients treated for oropharyngeal (mouth and throat) cancers linked to HPV infection suggests at least one of the antibodies could be useful in identifying those at risk for a recurrence of the cancer, say scientists at The Johns Hopkins University.

        The National Cancer Institute estimates that HPV now accounts for 80% of the incidence of oropharyngeal cancers in the United   States. While people with HPV-positive tumors of the throat, the base of the tongue, and the tonsils have higher overall survival rates compared to people with similar tumors not caused by HPV, recent data shows that more than 25 percent of HPV-positive cancers recur—usually within the first two years after treatment.

        “There are currently no reliable tests available to detect early recurrence, so we hope to find a biological marker that could help identify those most at risk,” explained lead study author Carole Fakhry, M.D., associate professor of otolaryngology–head and neck surgery at the Johns Hopkins University School of Medicine and Johns Hopkins Kimmel Cancer Center.

        In this new study, the Hopkins researchers focused their attention on the antibodies the body produces to fight HPV-related cancer proteins. Of particular interest to the investigators was the E6 immunoglobulin molecule, which is strongly associated with the diagnosis of HPV-positive oropharyngeal cancer.

        “To determine whether HPV antibody titers have a potential role as early markers of disease recurrence or prognosis, a retrospective pilot study was designed to determine whether HPV16 early antibody titers E6, E7, E1, and E2 decrease after treatment of HPV16-positive OPC (oropharyngeal cancer),” the authors wrote.

        The findings from this study were published recently in Cancer Prevention Research through an article entitled “Serum Antibodies to HPV16 Early Proteins Warrant Investigation as Potential Biomarkers for Risk Stratification and Recurrence of HPV-Associated Oropharyngeal Cancer.”

        The scientists postulated that the levels of the E6 antibody should fall when a patient is treated and cured of their cancer, while conversely an increase in a patient’s E6 levels after treatment could be indicative of a higher risk of the cancer returning.

        The investigators examined the health records and blood serum samples of 60 patients with HPV-positive oropharyngeal cancer and a median age of 56, mostly Caucasian men, who were treated at The Johns Hopkins Hospital. Three of the patients had samples taken before their treatment, 34 had samples collected up to six months after therapy, and 52 had samples taken six months or later after treatment. Among the 60 patients, Dr. Fakhry and her colleagues identified six cases of recurring cancer within an average of 4.4 years of follow-up after treatment.

        Strikingly, the researchers found that patients who had high levels of E6 antibody before their treatment were seven times more likely than those with lower levels to have their cancer return.

        The authors added that the “levels of antibodies to HPV16 early oncoproteins decline after therapy. Higher E6 titers at diagnosis are associated with significant increases in the risk of recurrence. These data support the prospective evaluation of HPV16 antibodies as markers of surveillance and for risk stratification at diagnosis.”

        At the moment, these HPV antibodies are not measured routinely in patients. However, the scientists noted that more research was needed to know whether such tests held value in determining the path of a patient’s follow-up care, such as whether and how often a patient might need imaging or clinical exams to watch for cancer’s possible return.

    “Potentially, a low-risk patient may need less stringent surveillance while a high-risk patient may require more intense imaging,” Dr. Fakhry remarked. “But this is far away from clinical practice, as we would really need to understand whether this hypothetical approach would improve lead time to diagnosis of recurrence and survival outcomes.”