The absence of high-risk human papillomavirus in Czech non-small cell lung cancer cases.

Hana Jaworek,Vladimira Koudelakova,Rastislav Slavkovsky,Marian Hajduch,Jiri Drabek

doi:10.5507/bp.2018.079

Hana Jaworek, Vladimira Koudelakova + Show 3 more

Open Access

https://doi.org/10.5507/bp.2018.079

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Abstract

The purpose of our study was to examine the presence of human papillomavirus (HPV) DNA in Czech patients with non-small cell lung cancer (NSCLC). A highly sensitive quantitative polymerase chain reaction (qPCR) detecting the E6 gene of HPV16, 18, 31, and 56 was designed. The limit of detection was assessed using serial dilutions of HPV-positive plasmids. The qPCR was validated on a set of 402 cervical swabs where the qPCR, Cobas, and PapilloCheck methods were tested in parallel. Finally, qPCR was used for HPV detection in a set of 80 patients with primary NSCLC, both from formalin-fixed paraffin-embedded (FFPE) and fresh frozen (FF) tissue samples. The qPCR method was able to reliably detect at least 4 copies of the E6 gene per reaction in HPV16, 18, and 31, and 40 copies per reaction in HPV56. The sensitivity and specificity of the qPCR were 75.6-99.3% and 63.9-100% respectively, depending on the HPV genotype and reference method used. HPV DNA was not detected in the FFPE and FF samples from the set of 80 NSCLC patients. No hrHPV DNA was found in primary NSCLC tumors from a Czech population.

Highlights

Lung cancer is the leading cause of cancer-related mortality worldwide
Plasmids containing human papillomavirus (HPV) DNA Plasmids containing HPV16, HPV18 (HPV18 purified plasmid DNA, ATCC® 45152DTM), and HPV56 (HPV56 clone 2C purified plasmid DNA, ATCC® 40549TM) genomes were purchased from ATCC (Rockville, MD); these plasmids were used to determine the limit of detection (LOD) of the quantitative polymerase chain reaction method developed for this study
Detection limit of the quantitative polymerase chain reaction (qPCR) method The limit of detection (LOD) for the qPCR method was determined using plasmid DNA containing the genomes of HPV16, 18, 31, and 56

Summary

Introduction

Lung cancer is the leading cause of cancer-related mortality worldwide. The pathogenesis of lung cancer is a complex interaction between environmental and genetic factors. The carcinogenic role of high-risk (hr) HPV infection has been demonstrated in almost all cervical carcinomas, and in a subset of oropharyngeal and anogenital (penile, vaginal, vulvar, and anal) cancers[3]. The respiratory tract is located close to the oropharynx, where HPV is a known causal agent of a subset of cancers[4]. Lung tumors have morphological similarities to anogenital cancers caused by HPV (ref.[7,8]). These facts led to the hypothesis that here is an association between HPV infection and lung cancer. Several studies have examined the impact of the HPV infection on lung cancer development, including large meta-analyses, but with conflicting results[9,10,11,12,13]

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