Abstract 4824: Little evidence of human papillomavirus in lung tumor tissue

Abstract

Abstract Background: Lung cancer kills over one million people worldwide each year. Human papillomavirus (HPV) has been proposed as a potential cause. Over 50 studies have evaluated HPV in lung tumor tissue over the last 20 years with mixed findings, but most were severely underpowered or had other methodological limitations. While several HPV-associated cancers have been identified (e.g., cervical, tonsillar), the role of HPV in lung carcinogenesis remains controversial. Methods: We tested 450 lung cancer cases in the Environment And Genetics in Lung cancer Etiology (EAGLE) Italian population-based, case control study for HPV DNA. DNA was extracted from ethanol or formalin-fixed, paraffin-embedded tumor tissue under strict PCR clean conditions and was evaluated for HPV16 and 18 by type-specific, real-time PCR targeted to the E6 or E7 gene. The number of cell equivalents evaluable in these reactions was estimated by real-time PCR targeted to the human ERV3 gene. DNA purity was assessed by standard spectrophotometry (260/280 ratio). Results: 79.6% (n=358) of the 450 cases were male, 48.9% (n=220) were current smokers, 44.0% (n=198) were former smokers, 6.7% (n=30) were never smokers, and 0.4% (n=2) had unknown smoking status. 399 of 450 cases (88.67%) met quality indices for DNA quantity (at least 100 evaluable cell equivalents) and quality (260/280 ratio of 1.5 to 2.2). Of these, 398 (99.75%, 95% confidence interval: 98.61%-99.99%) were negative for HPV16 and 18. One case, a female former smoker with adenocarcinoma, was positive for HPV16 at low copy number (0.4 per 1000 cell equivalents). We are currently evaluating a subset of cases (n=100) for a broad spectrum of HPV types by PCR with SPF10 primers and a cocktail of conservative probes recognizing at least 54 mucosal HPV genotypes in a microtiter plate format (DEIA). To date no HPV has been detected in the 30 cases tested. Conclusions: Using extensive laboratory efforts to avoid DNA contamination and sensitive HPV DNA detection assays, we found no evidence to support a role for HPV in lung cancer in a representative Western population. Our results provide the strongest evidence to date to rule out a role for HPV in lung carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4824.