Immunomarker Found for Recurring HPV-Linked Oropharyngeal Cancers

Human papilloma virus (HPV) infection antibodies in patients treated for oropharyngeal (mouth and throat) cancers (OPC) linked to HPV infection suggests at least one of the antibodies could be useful in identifying those at risk.

People with HPV-positive tumors of the throat, base of the tongue and tonsils have higher overall survival rates compared to people with similar tumors not caused by HPV, but studies show that more than 25% of HPV-positive cancers recur, usually within the first two years after treatment.

Scientists at the Johns Hopkins University School of Medicine (Baltimore, MD, USA) designed a retrospective study to determine whether HPV16 antibody titers change after treatment. Participants with HPV-OPC and two or greater serology specimens available were eligible. HPV16 tumor status was obtained from previously reported data which included real time polymerase chain reaction (qPCR) for HPV16 genomic DNA (≥0.1 copy per genome) and high risk HPV in situ hybridization. A subset analysis was restricted to participants with clinically available HPV16-positive in situ hybridization tumor status.

Antibodies to HPV16 E1, E2, E6, and E7 were measured by enzyme-linked immunosorbent assay (ELISA) using the glutathione S-transferase (GST) capture method with some modifications. The ELISA optical density (OD) was measured at 405 nm, with a reference wavelength of 490 nm, in an automated microtiter plate reader (Molecular Devices; Sunnyvale, CA, USA). The mean OD in wells with GST alone was subtracted from the mean OD in wells with the GST-HPV protein to give an antigen-specific OD value.

The team analyzed blood serum samples of 60 patients with HPV-positive oropharyngeal cancer and a median age of 56, mostly Caucasian men. There were 43, 34, and 52 subjects with serum samples available for pretreatment, early, and late posttreatment intervals. Mean pretreatment antibody levels were higher than posttreatment antibody levels. Average antibody levels decreased significantly over time for E6 and E7. Among the 60 patients, they identified six cases of recurring cancer within an average of 4.4 years of follow-up after treatment.

Carole Fakhry, MD, MPH, the lead author of the study, said, “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. Potentially, a low-risk patient may need less stringent surveillance while a high-risk patient may require more intense imaging.” The study was published online on December 31, 2015, in the journal Cancer Prevention Research.

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Johns Hopkins University School of Medicine 
Molecular Devices