Another prognostic tool may be in the offing for clinicians to use in evaluating patients with oropharyngeal cancers, new research suggests.
The presence in serum of three antibodies to human papillomavirus type 16 (HPV16) was predictive of better progression-free and overall survival in these patients, according to Kristina R. Dahlstrom, PhD, from the University of Texas MD Anderson Cancer Center, in Houston, and colleagues.
Patients whose serum was positive for the presence of three specific antibodies to “early” (E) proteins involved in replication and growth of HPV16 had dramatically better rates of overall survival (OS) and progression-free survival (PFS) compared with patients whose serum was negative for the antibodies, they reported online June 15 in Clinical Cancer Research.
Specifically, for those patients whose serum was positive for any E antibodies, 5-year estimated OS was 87.4%, compared with 42.2% for patients whose sereum was negative for all E antibodies (P < .001). The respective 5-year PFS rates were 82.9% and 46.1% (P < .001).
“These results hint at a prognostic stratification of patients with HPV-related oropharynx cancer reflecting humoral immune response to HPV type 16 E proteins and thus may help in choosing immunotherapy approaches for such patients in future,” said senior author Erich M. Sturgis, MD, MPH, a surgeon at MD Anderson, in comments to Medscape Medical News.
Currently, the serology results are not strong enough to be used as clinical decision tools for choosing current therapies, she added.
Their findings also suggest that vaccine-based immunotherapy targeted against HPV16 E-antigens combined with other immunotherapies such as checkpoint inhibitors might be effective against recurrent or metastatic HPV16-positive cancers of the oral cavity and pharynx, said Dr Sturgis.
The findings appear to further illuminate what is going on immunologically in these patients, said an expert not involved with the research.
“This is certainly an interesting study that builds upon our early understanding of the role of the host’s immune response in determining outcomes in HPV-associated oropharynx cancers,” commented Lori J Wirth, MD, a head and neck cancer specialist at the Massachusetts General Hospital Cancer Center, in Boston.
“We know from responses experienced by HPV-positive oropharyngeal squamous cell carcinoma patients enrolled in early clinical trials investigating checkpoint inhibitors that the host immune system can be exploited for a therapeutic end. The more we know about the host immune response to this virally mediated cancer, the better we’ll get at taking advantage of it,” she told Medscape Medical News.
More Cancers, Better Outcomes
Earlier studies have shown that although the incidence of HPV-related head and neck cancers is rising, patients with oropharyngeal squamous cell carcinomas positive for HPV16 have significantly better prognoses than patients with the same cancers not related to HPV infections.
To see whether they could identify prognostic biomarkers in patients with HPV-related oropharyngeal cancers, the investigators used enzyme-linked immunosorbent assasy to quantify immunoglobulin G antibodies to both early antigens (E1 and E4-E7) to the viral capsid proteins L1 and L2, and to the N-terminal and C-terminal fragments of E2 (NE2, CE2).
Among serum samples taken from 209 patients with oropharyngeal cancers at diagnosis, at the end of treatment, and during follow-up, PFS was significantly better for patients testing positive for any E antigen (P < .001), but not for patients testing positive for any L antigen. Therefore, for all subsequent analyses, the investigators focused only on patients testing positive for E antigens.
In multivariable models adjusted for age, smoking status, and treatment, the hazard ratio (HR) for death for patients with any E antibodies was 0.20 (95% confidence interval [CI], 0.1 – 0.4).
The HR for progression for those with any E antibodies was 0.20; (95% CI, 0.1 – 0.5).
The investigators also found that serum positivity for NE2, E1, and E6 were were all strongly associated with better OS and PFS, with respective HRs of 0.20, 0.30, and 0.30 (all significant, as shown by 95% CI).
“Specific antibody status has the potential to be a useful prognostic indicator that may identify subsets of patients diagnosed with HPV16-positive tumors who may benefit from altered monitoring and/or treatments. In addition, the suggestion that immune response to HPV16 antigens is important to cancer outcomes suggests the potential of augmenting immune responses to improve treatment of patients with HPV-driven oropharyngeal carcinoma,” the investigators write.
The study was supported by grants from the National Institutes of Health. Dr Sturgis and Dr Wirth have reported no relevant financial relationships.
Clin Cancer Res. 2015:21:2861-2869. Abstract
*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.