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HPV serum antibodies predict OS, PFS rates in oropharyngeal cancer
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HPV16-specific antibodies improved OS and PFS in patients with HPV-positive oropharyngeal squamous cell carcinoma, according to study results.
HPV-positive oropharyngeal carcinoma rates have greatly increased in recent years, according to study background. Oropharyngeal carcinoma positive for HPV16 has a significantly better prognosis than HPV-negative oropharyngeal cancer.
Erich M. Sturgis, MD, MPH, associate professor of head and neck cancer and epidemiology at The University of Texas MD Anderson Cancer Center, and colleagues investigated the biologic and prognostic relevance of serum antibodies related to HPV16 for patients with HPV-positive oropharyngeal cancer.
The analysis included 209 patients with previously untreated oropharyngeal carcinoma (median age, 55 years; 88% men). Researchers used a custom programmable enzyme-linked assay to screen serum samples from the patients for the immunoglobulin antibodies to the HPV16 antigens E1, E4-7, L1, L2 and the N- and C-terminal fragments of E2 (NE2, CE2).
Ninety-six patients had HPV-positive disease. Thirty-seven percent of patients reported 10 or more pack-years of smoking.
The researchers obtained samples at baseline, 6 weeks following the end of treatment and at 6-month intervals for up to 3 years. Overall, 90% of patients had any E antibody, 15.8% had any L antibody, 82.8% had NE2 and 48.3% had CE2 at baseline.
Median follow-up was 62.7 months (range, 3.9-96.9) for all surviving patients and 68.9 months (range, 4.1-92.5) for surviving patients with HPV16-positive tumors.
A greater proportion of patients positive for any E antibodies achieved 5-year OS (87.4% vs. 42.2%) and 5-year PFS (82.9% vs. 46.1%) than patients negative for E antibodies (P < .001 for both).
In a multivariable analysis, testing positive for any E antibodies conferred an 80% reduction in the risk for death (HR = 0.2; 95% CI, 0.1-0.4) and progression (HR = 0.2; 95% CI, 0.1-0.5).
Further, NE2 positivity, E1 positivity and E6 possibility reduced the risk for death by 80% and progression by 70%.
Among 130 patients with 10 or fewer pack years, E-positive antibodies reduced the risk for death (HR = 0.1; 95% CI, 0-0.7) and progression (HR = 0.1; 95% CI, 0-1). However, the researchers did not observe the strong associations between individual antibodies in this patient subset compared with the entire cohort.
The researchers found that E antibody positivity served as a better predictor for OS and PFS (P < .001 for both) than HPV positivity (OS, P = .031; PFS, P = .016). However, in a multivariable analysis, both factors conferred an 80% reduction in the risk for death and a strong association with improved PFS.
L antibodies did not exhibit an association with survival advantage, according to the researchers.
Researchers identified the large proportion of patients with HPV-negative tumors as a limitation to these findings. Further, a large subset of patients with HPV-positive tumors tested negative for E antibodies, suggesting potential misclassification.
“If this testing became commercially available it could not only be used as a means for identifying people who are at risk for oropharyngeal and other HPV cancers, but may also allow identification of HPV-related oropharyngeal cancer patients at greater or lower risk for cancer recurrence and death,” Sturgis said in a press release. “These data further suggest that if we can modify patient immunity and increase a patient’s E antibody response, we might be able to affect cancer outcomes. Clinical trials are now testing whether vaccines that can stimulate these antibodies have clinical utility in HPV-related cancers.” – by Cameron Kelsall
Disclosure: Sturgis reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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