Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus–related oropharyngeal cancer

• Published in: Cancer Vol. 123; no. 24; pp. 4886 - 4894
• Main Authors: Dahlstrom, Kristina R., Anderson, Karen S., Field, Matthew S., Chowell, Diego, Ning, Jing, Li, Nan, Wei, Qingyi, Li, Guojun, Sturgis, Erich M.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.12.2017
• Subjects: Academic Medical Centers; Adult; Age Distribution; Aged; Antibodies; Antibodies, Viral - blood; Antigens; Biopsy, Needle; Cancer; Case-Control Studies; Clinical trials; Confidence intervals; Control methods; Diagnostic systems; Enzyme-Linked Immunosorbent Assay; Epidemics; Female; Head; Head & neck cancer; head and neck neoplasms; Health risk assessment; Health risks; Human papillomavirus; Human papillomavirus 16 - genetics; Human papillomavirus 16 - isolation & purification; Humans; Immunoglobulins; Immunohistochemistry; In Situ Hybridization; Incidence; Logistic Models; Male; Medical diagnosis; Middle Aged; Oncology; Oropharyngeal cancer; Oropharyngeal Neoplasms - diagnosis; Oropharyngeal Neoplasms - epidemiology; Oropharyngeal Neoplasms - virology; Papillomavirus Infections - complications; Papillomavirus Infections - diagnosis; papillomavirus oncogene proteins; Patients; Prognosis; Reference Values; Regression analysis; Regression models; Risk; Risk Assessment; Screening; Sensitivity; Sensitivity and Specificity; Serology; serum antibodies; Sex Distribution; Statistical analysis; Texas; Throat cancer; head and neck neoplasms; papillomavirus oncogene proteins; oropharyngeal cancer; serum antibodies; human papillomavirus
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.30955

BACKGROUND Because of the current epidemic of human papillomavirus (HPV)–related oropharyngeal cancer (OPC), a screening strategy is urgently needed. The presence of serum antibodies to HPV‐16 early (E) antigens is associated with an increased risk for OPC. The purpose of this study was to evaluate the diagnostic accuracy of antibodies to a panel of HPV‐16 E antigens in screening for OPC. METHODS This case‐control study included 378 patients with OPC, 153 patients with nonoropharyngeal head and neck cancer (non‐OPC), and 782 healthy control subjects. The tumor HPV status was determined with p16 immunohistochemistry and HPV in situ hybridization. HPV‐16 E antibody levels in serum were identified with an enzyme‐linked immunosorbent assay. A trained binary logistic regression model based on the combination of all E antigens was predefined and applied to the data set. The sensitivity and specificity of the assay for distinguishing HPV‐related OPC from controls were calculated. Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals for the association of head and neck cancer with the antibody status. RESULTS Of the 378 patients with OPC, 348 had p16‐positive OPC. HPV‐16 E antibody levels were significantly higher among patients with p16‐positive OPC but not among patients with non‐OPC or among controls. Serology showed high sensitivity and specificity for HPV‐related OPC (binary classifier: 83% sensitivity and 99% specificity for p16‐positive OPC). CONCLUSIONS A trained binary classification algorithm that incorporates information about multiple E antibodies has high sensitivity and specificity and may be advantageous for risk stratification in future screening trials. Cancer 2017;123:4886‐94. © 2017 American Cancer Society. The presence of serum antibodies to human papillomavirus 16 early antigens may be used to identify at‐risk individuals who would benefit from further screening. A trained algorithm that incorporates information about multiple early antibodies shows high sensitivity and specificity and may be advantageous for risk stratification in future screening trials.