Development of Glioblastoma Multiforme in Patients With Human Papillomavirus-Positive Oropharyngeal Squamous Cell...

Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPC) patients typically exhibit reduced rates of second primary malignancies (SPMs) compared to HPV-negative head and neck cancer patients. While HPV+ OPC patients may be predisposed to SPMs in HPV-associated anatomical sites, the metachronous presentation of an HPV+ OPC and subsequent glioblastoma multiforme (GBM) has not been previously documented.

We present two cases of HPV+ OPC patients who developed GBMs within a short period after definitive therapy.

Comprehensive whole exome sequencing (WES) was performed on paired GBM, oropharyngeal, and matched normal tissues from two HPV+ OPC patients who developed GBMs within a short period after definitive therapy, with the goal of identifying shared somatic and germline variants. Bioinformatic analyses included variant calling, annotation, and pathway enrichment.

WES revealed a shared CEP104 missense mutation among both oropharyngeal tumors as well as a potential KIR2DL4 germline variant in the second patient, suggesting a possible role for disrupted NK cell immunity in driving these cancers.

Although these cases were likely random events, they illustrate the diagnostic and therapeutic challenges of GBM following HPV+ OPC and underscore the importance of personalized genomic assessment in HPV+ OPC survivors, who may develop non-head and neck SPMs unrelated to field cancerization.