Assessment of human papilloma virus in non-small cell lung cancer in never-smokers: A study from a prospective registry of never-smokers.

Abstract

e18126 Background: Driver mutations have been identified in most non-small cell lung cancers (NSCLC) from never-smokers. However, a small percentage of the tumors still have no its mutations detected. Human papillomavirus (HPV) has been hypothesized to contribute to lung carcinogenesis in East Asia. Methods: We started a prospective registry of never-smokers with NSCLC at the Kinki-chuo Chest Medical Center, Japan, in 2008. We consecutively enrolled all the never-smokers after obtaining written informed consent. Among these, we selected the 114 patients treated with surgery to obtain a large amount of DNA. After exclusion of samples with suboptimal quality, DNA was extracted from 93 formalin-fixed paraffin-embedded surgical tissues. HPV genotyping was performed using a PCR-based microarray system for detecting 23 HPV types, including high-risk (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk or risk-unknown types (HPV types 6, 11, 30, 34, 40, 42, 53, 54, 61, and 66). Epidermal growth factor receptor (EGFR) and KRAS mutations were examined with real time PCR (genotyping), and EML4-ALK rearrangements were detected using immunohistochemical staining and fluorescence in-situ hybridization. Results: There were 80 female (86.0%) and 13 male patients (14.0%), with a median age of 67 years (range 29-83). Almost all cases were of the adenocarcinoma histological subtype (92.5%). Molecular analysis of these 93 patients detected 59 EGFR mutations (63.4%), 5 K-ras mutations ( 5.4% ) and 4 EML4-ALK rearrangements (4.3%). These abnormalities were mutually exclusive except for one case who had both EGFR and KRAS mutations. HPV 6 was detected in only one case (1.1%), a 49-year-old female who had an EGFR mutation with wild type KRAS and ALK. No others examined were positive for any HPV type. Conclusions: The three driver mutations accounted for 72.0% of NSCLC in never-smokers. Although a low-risk HPV type was evident in one case, no high-risk HPV types were detected in the tumors with or without the mutations. Our results suggest that HPV does not play a major role as the driving oncogenic event in adenocarcinoma in never-smokers in Osaka, the central area of Japan.