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Risk factors and survival by HPV‐16 E6 and E7 antibody status in human papillomavirus positive head and neck cancer
Authors:Elaine M. Smith  Michael Pawlita  Linda M. Rubenstein  Thomas H. Haugen  Eva Hamsikova  Lubomir P. Turek
Affiliation:1. Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IATel: 319‐384‐5014, Fax: 319‐384‐5031;2. Department of Genomic Modification and Carcinogenesis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany;3. Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA;4. Veterans Affairs Medical Center and Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA;5. Department of Experimental Virology, Institute of Hematology and Blood Transfusion, U nemocnice 1, Prague, Czech Republic
Abstract:High‐risk human papillomavirus types (HPV‐HR) are associated with head and neck cancer (HNC) risk and better survival. Most patients with HPV‐HR DNA‐positive tumors develop anti‐HPV E6/E7 antibodies; however, it is unclear whether those who mount an immune response have similar risk factors or clinical outcomes as those who do not. HPV‐16 DNA tumor‐positive HNC cases were evaluated for HPV‐16 E6 and E7 antibodies using a GST capture ELISA system. Among 57 HPV‐16 DNA tumor‐positive HNC cases, 67% were detected with HPV‐16 E6 and/or E7 antibodies. Male gender (76% vs. 42%, p = 0.02), younger age (63% vs. 16%, p = 0.001) but not tobacco or alcohol were associated with E6 and/or E7 seropositivity. Seropositivity was associated more often with late stage (76%), poor grade (65%), positive nodes (82%). and in the oropharynx (82%), Median disease‐specific and recurrence‐free survival were longer in E6 and/or E7 seropositive compared to E6/E7‐negative cases (2.2 years vs. 1.4 years, both outcomes), although results were not statistically significant. When examined jointly with p16 expression, E6 and/or E7‐positive/p16‐positive cases had better disease‐specific (2.1 years vs. 1.1 years, p = 0.06) and recurrence‐free (2.3 years vs. 1.1 years, p = 0.03) survival compared to E6‐/E7‐/p16‐ cases. These findings suggest there are 2 distinct HNC patient groups with HPV DNA‐positive tumors, distinguishable by E6 and/or E7 antibody status. Differences in antibody status are associated with distinct risk factors and clinical outcomes. This information can be available as a simple blood test at initial presentation, before the removal of tissue through biopsy or surgery.
Keywords:head and neck cancer  HPV‐16 E6  E7 antibodies  HPV  survival  risk factors
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