Highly sensitive deep panel sequencing of 27 HPV genotypes in prostate cancer biopsies results in very low detection rates and indicates that HPV is not a major etiological driver of this malignancy

Human papillomavirus (HPV) has been proposed to contribute to the carcinogenesis of prostate cancer. However, previous studies have yielded conflicting results. This study aims to add useful information to the ongoing discussion concerning the association between HPV infection and prostate cancer. We used two high-throughput next-generation sequencing (NGS) approaches to detect HPV RNA in malignant and adjacent normal (AN) prostate tissue (cohorts 1 and 2) and HPV DNA from carcinogenic and probably/possibly carcinogenic-classified HPV types (cohort 3) in malignant prostate, AN prostate, and benign prostatic hyperplasia (BPH) tissues. In total, 0% (cohort 1: 0/83, cohort 2: 0/16) of the malignant prostate tissue samples and 0% (cohort 1: 0/23, cohort 2: 0/8) of the AN prostate tissue samples were positive for HPV RNA. A total of 8.3% (1/12) of the BPH samples, 0% (0/28) of the AN samples, and 0.8% (1/132) of the malignant prostate samples were positive for HPV16 DNA. However, the normalized read count of the HPV16-positive malignant sample was close to the cut-off. In addition, no other carcinogenic-classified HPV types were detected in any of the BPH, AN, or malignant prostate tissue samples. Our study does not support HPV infection as a major contributor to the etiology of prostate cancer.