No Causal Association Identified for Human Papillomavirus Infections in Lung Cancer

Abstract

Human papillomavirus (HPV) infections have been implicated in lung carcinogenesis, but causal associations remain uncertain. We evaluated a potential causal role for HPV infections in lung cancer through an analysis involving serology, tumor DNA, RNA, and p16 protein expression. Association between type-specific HPV antibodies and risk of lung cancer was examined among 3,083 cases and 4,328 controls in two case-control studies (retrospective) and one nested case-control study (prospective design). Three hundred and thirty-four available tumors were subjected to pathologic evaluation and subsequent HPV genotyping following stringent conditions to detect all high-risk and two low-risk HPV types. All HPV DNA-positive tumors were further tested for the expression of p16 protein and type-specific HPV mRNA. On the basis of the consistency of the results, although HPV11 and HPV31 E6 antibodies were associated with lung cancer risk in the retrospective study, no association was observed in the prospective design. Presence of type-specific antibodies correlated poorly with the presence of the corresponding HPV DNA in the tumor. Although nearly 10% of the lung tumors were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes. No association was observed between HPV antibodies or DNA and lung cancer survival. In conclusion, we found no supportive evidence for the hypothesized causal association between HPV infections and lung cancer. Cancer Res; 74(13); 3525-34. Ó2014 AACR.

Human papillomavirus infection as a prognostic marker for lung adenocarcinoma: a systematic review and meta-analysis

“…Eleven of these 19 articles were subsequently excluded for various reasons, including two reviews, eight that did not provide HR s and one that was not based on lung cancer. Finally, eight eligible articles were included in this systematic review and meta-analysis [15–22]. …”

“…Among these articles, five studies were conducted in China [16–18, 21, 22], two in Japan [19, 20] and one in Russia [15]. Of all the selected articles, three evaluated HR s [15, 16, 21], while in the other five articles [17–20, 22], HR s were absent, and needed to be calculated from the survival curves. Three articles did not give accurate data for follow-up [16, 19, 20].…”

Up-Regulation of FOXM1 by E6 Oncoprotein through the MZF1/NKX2-1 Axis Is Required for Human Papillomavirus–Associated Tumorigenesis

“…Therefore, we suggest that FOXM1 might be potentially targeted to suppress tumor progression and metastasis and, in turn, to improve outcomes in patients with HPV 16/18 infection. The association of HPV infection with cervical and oral cavity cancers has been documented [1], [2], [3], [4]; however, the association between HPV infection and lung cancer is still debated [25], [26], [27]. The involvement of HPV infection in Taiwanese lung tumorigenesis has been extensively studied [5], [6], [7], although the negative correlation between HPV infection and lung cancer has been reported elsewhere [25], [26], [27].…”

The most important questions in cancer research and clinical oncology

“…These results indicate that HPV antibodies are substantially increased in lung cancer patients compared with hospital-based controls, none of whom reported a previous cancer history or any tobacco-related disease. They subsequently reported that “although nearly 10% of the lung tumours were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes” [32]. It should however be noted that all these studies were performed in Europe.…”