Prevalence and Genotype Distribution of Human Papillomavirus in Primary Lung Cancer in Eastern India

Lung cancer is the leading cause of cancer-associated mortality globally, with approximately 2.5 million new cases and 1.8 million deaths. It accounts for approximately one in five cancer-related deaths worldwide. While tobacco smoking is the main cause of lung cancer, many cases occur in never-smokers, indicating that other environmental, genetic, and infectious contributors may play a role. High-risk human papillomavirus (HPV), particularly HPV-16 and -18, is a known etiologic agent in cervical, anogenital, and oropharyngeal malignancies. The pathogenic role of HPV in lung cancer remains controversial, mainly due to significant geographical variation in prevalence and inconsistent detection rates, despite increasing molecular evidence of HPV DNA in primary lung tumors. Information about HPV-related lung cancer in India is scarce.

This study aims to determine the prevalence of high-risk HPV types 16 and 18 in primary lung cancer tissue samples and to evaluate their potential associations with clinicodemographic characteristics.

A retrospective cross-sectional study was conducted using samples collected between January 2023 and October 2025 at a tertiary care teaching hospital in eastern India. A total of 95 archival formalin-fixed paraffin-embedded (FFPE) tissue specimens from histopathologically confirmed primary lung neoplasms were included in the study. DNA was extracted from FFPE tissues and subjected to real-time polymerase chain reaction for HPV-16 and HPV-18. We compared clinicodemographic variables between HPV-positive and HPV-negative patients.

HPV-16 DNA was detected in 29 of 95 (30.5%) lung cancer specimens, whereas HPV-18 was not detected in any case. Squamous cell carcinoma showed a higher HPV-16 positivity rate than adenocarcinoma (42.1% vs. 26.8%), although the difference was not statistically significant. HPV-positive patients had a mean age of 64 years and were predominantly male. Smoking was significantly associated with HPV positivity (p = 0.035). Most HPV-positive tumors involved the right lung and occurred among rural residents.

Of primary lung cancers in this cohort, one third were HPV-16 positive, and none were HPV-18 positive. These findings suggest a possible association between HPV-16 infection and pulmonary carcinoma, particularly among smokers. Future larger multicenter studies may clarify the biological relevance of HPV in lung carcinogenesis by incorporating detailed viral oncogene expression and genotyping.