Human Papillomavirus and Human Cytomegalovirus Infection and Association with Prognosis in Patients with Primary Glioblastoma in Pakistan

Abstract

Objective: Glioblastoma multiforme (GBM) is the most common adult primary brain tumor. Human cytomegalovirus (HCMV) has been studied for the past decade, and conflicting results have been reported with no conclusive role established yet. Human papillomavirus (HPV) is involved in the pathogenesis of many cancers and has a high prevalence in patients with cervical and oral cancer in Pakistan. The objective of our study was to identify the prevalence of HCMV and HPV in Pakistani patients with primary GBM. Methods: In total, 112 primary GBM biopsies were analyzed. HCMV and HPV infection was investigated using nested and conventional polymerase chain reaction, respectively. Positive HPV samples were further confirmed through sequencing. HPV status was correlated with histology and expression of other frequently mutated GBM molecular markers. Results: Our study comprised of 68% male and 32% female patients. HCMV was detected in only 1 patient whereas HPV infection was present in 28% of patients with no cases of HPV and HCMV coinfection. We report for the first time that a majority of HPV-positive patients with GBM harbored types 16 and 18 both. Among them, 16% were HPV-type 16 and 20% were HPV-type 18. Patients infected with HPV had longer survival times, but this was not statistically significant. The most commonly overexpressed molecular marker in HPV-positive patients was cyclo-oxygenase-2, and no histologic changes were seen in HPV-positive GBM cases. Conclusions: The presence of a single HCMV positive is intriguing. In addition, we discovered a substantially high 28% prevalence of HPV in GBM patients. The role of viruses in gliomagenesis warrants further investigation.