Detection of Immunoglobulin G against E7 of Human Papillomavirus in Non-Small-Cell Lung Cancer

Background. A significant number of non-small-cell lung cancers (NSCLC) have human papillomavirus (HPV) DNA integrated in their genome. This study sought to further establish HPV’s possible etiologic link to NSCLC by evaluating an immune response to HPV’s oncogene, E7, in patients with NSCLC. Patients and Methods. Antibodies (IgG) in serum against E7 for HPV 16 and 18 in 100 patients with NSCLC were examined by enzyme-linked immunosorbent assay (ELISA). Results. Sixteen NSCLC patients were found to have a high titration of IgG for HPV oncogenic E7 protein. 23.5% of adenocarcinomas (AC,) and 15.4% of squamous cell carcinomas (SCC) were positive for IgG against HPV E7. HPV-18 (11%) had a slightly higher frequency than HPV-16 (6%). Of the six positive cases for HPV-16, 3 were AC, 2 SCC, and 1 NOS (not otherwise specified). For the 11 HPV-18 positives, 7 were AC, and 4 SCC. The one case with IgG against HPV 16 and 18 was AC. One case had high cross-reactive levels against E7 of HPV 16 and 18. Two (28%) of 7 patients who reported never smoking were positive for HPV, and 12 (13.6%) of 88 smokers were HPV positive. Conclusions. The study detected high levels of IgG against E7 in 16% of NSCLC patients. This adds evidence to a potential role of HPV in the pathogenesis of NSCLC. 1. Introduction Lung cancer remains the leading cause of cancer-related deaths worldwide, causing over a million deaths per year worldwide, with an estimated 221,130 new cases and 156,940 deaths in 2011 in the United States [1]. Ten to 20 percent of patients with NSCLC have never smoked [2]. Besides active smoking other etiologic risk factors for NSCLC are known (e.g., toxins, radon, and air pollution); human papilloma virus (HPV) also has been proposed as a potential cause for NSCLC [3]. In his meta-analysis of studies that have looked for detection of HPV in lung cancer, it was noted that HPV detection rates in bronchial carcinomas were found to be highly variable, ranging from 0 percent to 100 percent. On average, of 2,468 bronchial carcinomas, HPV DNA has been reported in 536 (21.7%) of squamous and nonsquamous NSCLC histologies [3]. The genome of HPV is a circular double-stranded DNA molecule of approximately 8000？bp. The open reading frames (ORF) include E1, E2, E4, E5, E6, and E7, which are expressed at different stages during epithelial differentiation. The high-risk HPV E6 and E7 ORF encode the viral oncoproteins that are invariably expressed in HPV-positive human cancers. E6 and E7 joint expression is necessary and sufficient for the immortalization of primary human