Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Feb;9(2):135-41.
doi: 10.1158/1940-6207.CAPR-15-0299. Epub 2015 Dec 23.

Serum Antibodies to HPV16 Early Proteins Warrant Investigation as Potential Biomarkers for Risk Stratification and Recurrence of HPV-Associated Oropharyngeal Cancer

Carole Fakhry  1 , Jesse R Qualliotine  2 , Zhe Zhang  3 , Nishant Agrawal  2 , Daria A Gaykalova  2 , Justin A Bishop  4 , Rathan M Subramaniam  5 , Wayne M Koch  2 , Christine H Chung  3 , David W Eisele  2 , Joseph Califano  2 , Raphael P Viscidi  6
Affiliations

Serum Antibodies to HPV16 Early Proteins Warrant Investigation as Potential Biomarkers for Risk Stratification and Recurrence of HPV-Associated Oropharyngeal Cancer

Carole Fakhry et al. Cancer Prev Res (Phila). 2016 Feb.

Abstract

Human papillomavirus (HPV) is responsible for increasing incidence of oropharyngeal cancer. At present, there are no biomarkers in the surveillance algorithm for HPV-positive oropharyngeal cancer (HPV-OPC). HPV16 E6 antibody precedes oropharyngeal cancer diagnosis. If HPV16 E6 indeed precedes primary diagnosis, it is similarly expected to precede disease recurrence and may have a potential role as a biomarker for surveillance of HPV-OPC. 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. Trends in pretreatment, early (≤6 months after treatment), and late posttreatment (>6 months after treatment) HPV16 antibody titers were examined. 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 (Ptrend = 0.001) and E7 (Ptrend < 0.001). Six disease recurrences were observed during the follow-up period (median, 4.4 years). In univariate analysis, a log-unit increase in pretreatment E6 titer was significantly associated with increased risk of disease recurrence (HR, 5.42; 95% CI, 1.1-25.7; P = 0.03). Therefore, 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.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest disclosures: None

Figures

Figure 1
Figure 1. Antibody levels by treatment period
The length of the box is the inter-quartile range and represents the middle 50% of antibody levels. The horizontal line inside the box depicts the median. The lower and upper hinges of the box represent the 25th and 75th percentiles, respectively. The vertical dashed lines extend from the box to the upper and lower 1.5 inter-quartile values from the upper and lower hinges. The filled circles represent the actual antibody levels. Significant change from pre-treatment (P<0.05) is indicated by asterisk (*).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gillison M, Chaturvedi A, Anderson W, Fakhry C. The epidemiology of HPV-positive head and neck squamous cell carcinoma. Journal Clinical Oncology. 2015;33:3235–42. - PMC - PubMed
    1. Fakhry C, Andersen KK, Eisele DW, Gillison ML. Oropharyngeal cancer survivorship in Denmark, 1977–2012. Oral oncology. 2015;51:982–984. - PubMed
    1. Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. Journal of Clinical Oncology. 2008;26:612–619. - PubMed
    1. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. Journal of clinical oncology. 2011;29:4294–4301. - PMC - PubMed
    1. Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. Journal of the National Cancer Institute. 2008;100:261–269. - PubMed

Publication types

MeSH terms