Assessment of human papillomavirus and Epstein-Barr virus in lung adenocarcinoma

Abstract

Abstract. The association of human papillomavirus (HPV) and Epstein-Barr virus (EBV) infection with non-small cell lung cancer is controversial. HPV and EBV prevalence in a uniform population of lung adenocarcinoma was investigated, hypothesizing that there would be differences seen between smokers and non-smokers and between sexes. Patients involved in this study were selected from a single institution database of lung cancer. In total 497 patients with adenocarcinoma were identified and 110 patients had sufficient tissue for analysis with an in situ hybridization method that probed for high-risk and low-risk HPV and EBV. There were 65 males and 45 females, 78 patients with stage I-IIIA disease and 32 patients with stage IIIB-IV disease. There were similar number of smokers and non-smokers. Across all stages HPV and EBV staining was absent from all tissues examined. It is unlikely that HPV or EBV is an important etiological agent in adenocarcinoma of the lung, even among the neversmokers. IntroductionCigarette smoke is strongly associated with the development of lung cancer (1). While the epidemic of smoking has reduced through public health awareness programs and education, the incidence of lung cancer remains unabated. There has been a demographic change in the global pandemic with a global realignment of histological subtypes. Adenocarcinoma incidence is rising globally among both smokers and nonsmokers. Up to 30% of all diagnosed non-small cell lung cancer (NSCLC) among various Asian countries, including Singapore, do not have a history of exposure to cigarette smoking. These patients tend to be predominantly female and have adenocarcinoma (2). This has given rise to different postulates as to the possible etiologies of NSCLC in this distinct of patients, ranging from exposure to cooking oil fumes (3,4), as well as diet and cancer susceptibility genotypes among Asians (5-7). Human papillomavirus (HPV) and Epstein-Barr virus (EBV) have been variously described to be associated and causative with several cancers. HPV is likely to be causal in cervical carcinoma and head and neck squamous cell carcinoma (HNSCC), and EBV in nasopharyngeal carcinoma. There have been various reports of association between HPV and EBV with lung cancer but results have not been conclusive (8). Leveraging on the excess of non-tobacco related lung cancer in our patients we investigated HPV and EBV prevalence in a uniform population of adenocarcinoma of the lung, hypothesizing that there would be differences seen between smokers and nonsmokers and between sexes. Patients and methodsPatients. Patients involved in this study were selected from a database of NSCLC patients, diagnosed in a single institution (SGH) from 1999 to 2002. The study had the approval of the Institutional Review Board of National Cancer Centre Singapore. The main selection criterion was a diagnosis of adenocarcinoma. Four hundred and ninety-seven patients were identified and among them, 110 patients had sufficient tissue blocks available for our analysis using in ...

HPV Analysis in Distinguishing Second Primary Tumors From Lung Metastases in Patients With Head and Neck Squamous Cell Carcinoma

“…Results based on in situ hybridization suggest that PCR-based analysis may vastly overestimate the frequency and relevance of HPV in primary lung cancers. Lim et al were unable to detect any HPV-positivity among 110 primary lung adenocarcinomas,(26) and we did not detect HPV among a broader range of primary lung carcinomas types including SqCCs with the basaloid phenotype – a phenotype that is commonly associated with HPV infection in non-pulmonary sites including the oropharynx, vulva, penis and anus. (6,11,13,21)…”

Epstein–Barr virus microRNAs and lung cancer

“…Two previous serologic studies found a higher seroprevalence of several EBV antibodies in lung cancer cases compared with healthy controls (Desgranges and de-The, 1979; Roy et al , 1994). Among tissue-based studies, some studies have found 5–10% positivity by EBER ISH or EBV nuclear antigen IHC (Kasai et al , 1994; Wong et al , 1995; Grinstein et al , 2002), whereas others have found no positivity by EBER ISH (Conway et al , 1996; Kijima et al , 2001; Hayakawa et al , 2003; Chu et al , 2004; Lim et al , 2009) and generally low or no positivity by other markers (Chu et al , 2004). Although EBER ISH is considered the gold standard for detecting EBV-associated cancers because of its high abundance in latently EBV-infected cells, it is not a perfect measure (Delecluse et al , 2007).…”

“…It has also been implicated in ∼10% of gastric cancers (Young and Rickinson, 2004). Although lung cancer cases in serological studies had higher EBV seropositivity than healthy controls (Desgranges and de-The, 1979; Roy et al , 1994), previous studies of EBV in lung tumour tissue have generally produced negative results, except in rare cases of lymphoepithelioma-like carcinomas (LELCs) (Chu et al , 2004; Lim et al , 2009). However, previous studies largely tested for expression of EBV-encoded small RNA ( EBER ), which is generally abundantly expressed in cells with latent EBV infection but occasionally may be absent or heterogeneously expressed in EBV DNA-positive tumours (Iwakiri and Takada, 2010).…”

Second primary esophageal or lung cancer in patients with head and neck carcinoma in Taiwan: incidence and risk in relation to primary index tumor site

“…In Taiwan, EBV is the most important etiological factor for NPC; circulating EBV DNA levels are positively correlated with disease stage and prognosis (Lin et al 2001;Lin et al 2004). On the other hand, EBV is not an etiological agent in lung or esophageal cancer (Lim et al 2009;Sunpaweravong et al 2005;Yanai et al 2003). The exclusive role of EBV in the pathogenesis might explain the distinct patterns of second primaries in NPC (Chen et al 2008).…”