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HPV Serum Antibodies May Predict Survival and Disease Progression in Patients With HPV-Positive Oropharyngeal Cancer

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Key Points

  • Patients with HPV-16-positive oropharyngeal carcinoma have significantly better survival than patients with HPV-16-negative oropharyngeal carcinoma.
  • The 5-year overall survival estimate for patients positive for E antibodies was 87.4% compared with 42.2% for patients negative for E antibodies. The 5-year progression-free survival estimate was 82.9% for antibody-positive patients compared with 46.1% for antibody-negative patients. Patients with HPV-positive disease who were also positive for NE2, E1, or E6 antibodies had an 80% reduced risk of death and a 70% reduced risk of disease progression.
  • Differential serologic responses in patients may reflect differential biologic processes within the host and tumor and may have prognostic value. 

A study by Dahlstrom et al investigating the usefulness of serum antibodies to human papillomavirus (HPV)-16 DNA antigens as predictors of survival for patients with oropharyngeal carcinoma has found that E1, NE2, and E6 antibody positivity were all strongly associated with improved overall and progression-free survival among patients with HPV-related oropharyngeal cancer. Serum antibodies to HPV-16 DNA antigens, particularly E1, NE2, and E6, have prognostic significance for patients with the cancer, according to the study findings. The study is published in Clinical Cancer Research.

Study Methodology

The researchers used blood samples from 209 patients with newly diagnosed, histopathologically confirmed, and previously untreated oropharyngeal carcinoma who participated in a large prospective epidemiologic study of head and neck cancer at The University of Texas MD Anderson Cancer Center between January 2006 and September 2008. Of the 209 patients, 114 had tumor HPV-16 status available for subgroup analyses; 96 had HPV-16-positive tumors.

The median follow-up time for patients who survived was 62.7 months (range, 3.996.9 months). The median follow-up time for patients with HPV-16-positive tumors who survived was 68.9 months (range, 4.192.5 months). There was no difference with respect to survival between patients who had tumor HPV-16 status available and those who did not (P = .577).

Blood samples were screened for HPV-16 antibodies E1, E4–7, L1, L2, and the N-terminal and C-terminal fragments of E2. The samples were taken as part of the patients’ initial workup, 6 weeks after the end of treatment, and at 6-month intervals for up to 3 years.

Key Findings

Patients who were positive for E1, NE2, and E6 antibodies had improved overall and progression-free survival (P < .05). For both overall and progression-free survival among HPV-positive patients, hazard ratios were 0.2 for NE2, 0.3 for E1, and 0.3 for E6 antibody positivity.

The 5-year overall survival estimate for patients positive for E antibodies was 87.4% compared with 42.2% for patients negative for E antibodies. The 5-year progression-free survival estimate was 82.9% for antibody-positive patients compared with 46.1% for antibody-negative patients.

Patients with HPV-positive disease who were also positive for NE2, E1, or E6 antibodies had an 80% reduced risk of death and a 70% reduced risk of disease progression. No survival advantage was noted for the L antibodies tested in the study.

Study Implications

“We found that patients who were seriologically positive to the E proteins of HPV-16 had a better prognosis than those patients who were seronegative to these antigens,” said Erich M. Sturgis, MD, MPH, a coauthor of the study and Professor in the Department of Head and Neck Surgery at The University of Texas MD Anderson Cancer Center, in a statement. “This seemed particularly true of patients who had tumors that we could confirm were HPV-positive. If this testing became commercially available, it could not only be used as a means of 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.”

He continued, “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-relative cancers.”

Erich M. Sturgis of The University of Texas MD Anderson Cancer Center is the corresponding author of this study.

Karen S. Anderson, MD, PhD, is a consultant/advisory board member for and has ownership interest in Provista Dx; Marshall Posner, MD, is a co-inventor on a patent for the serologic test, which is owned by Arizona State University. The remaining study authors reported no conflicts of interest.

Funding for this study was provided by the National Institutes of Health, The University of Texas MD Anderson Cancer Center, Arizona State University Institutional funds, the National Cancer Institute Early Detection Research Network, and the Stiefel Oropharyngeal Research Fund. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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