# Does a Transcriptionally Active HPV Infection Affect the Invasiveness of Pituitary Neuroendocrine Tumors? A Case Series Study of 60 Patients in Krakow, Poland

## TL;DR

This study explores whether active HPV infections in pituitary tumors are linked to reduced tumor invasiveness in 60 patients from Krakow.

## Contribution

The study is the first to investigate the association between transcriptionally active HPV infections and pituitary tumor invasiveness.

## Key findings

- Transcriptionally active HPV was detected in 18.3% of pituitary tumors.
- HPV-positive tumors showed significantly lower invasiveness on Knosp and Hardy scales.
- Further research is needed to confirm the role of HPV in tumor behavior.

## Abstract

Invasiveness of pituitary neuroendocrine tumors (PITNETs) is a major cause of recurrence and the risk of reoperation. Therefore, identification of specific biomarkers for the diagnosis and effective treatment of invasive PITNETs is of a great clinical importance. The aim of our retrospective study was to assess the potential of transcriptionally active HPV infection as a prognostic factor for PITNET invasiveness expressed in Knosp and Hardy scales. Among 60 PITNETs, a transcriptionally active high-risk HPV infection was detected in 11 tumors (18.3%). This infection was associated with a significantly lower probability of tumor invasiveness, measured on the Knosp and Hardy scales. Our results suggest that this transcriptionally active HPV infection may influence the invasiveness of pituitary adenomas; however, further studies are needed to confirm these results.

Background/Objective: Pituitary neuroendocrine tumors (PITNETs) often show a tendency towards invasive behavior, i.e., an invasion towards the cavernous sinuses or destruction of the sella turcica. In the present study, we analyzed whether a transcriptionally active HPV infection affects the invasiveness of pituitary tumors. Methods: Sixty patients with different phenotypes of PITNETs who underwent neurosurgery were studied. The obtained postoperative material was analyzed histopathologically. For each patient, formalin-fixed paraffin-embedded blocks were cut into ultra-thin slices and two to three of them were designated for DNA extraction, while one was used for histological slides. Based on the isolated DNA, the presence of DNA from individual HPV types was determined by the real-time detection polymerase chain reaction using the REALQUALITY RQ-Multi HPV Detection reagent kit (AB ANALITICA, Italy). P16 protein expression was assessed by immunohistochemical staining on the histological slides. A transcriptionally active infection with individual HPV types was distinguished when HPV DNA and P16 protein overexpression were detected simultaneously for a given tumor. Results: In the group of the 60 analyzed PITNETs, a transcriptionally active high-risk HPV infection was detected in a subset of 11 tumors (18.3%). This infection was associated with a significantly lower probability of tumor invasiveness, measured on both the Knosp (OR = 0.11, 95% CI: 0.02–0.58) and Hardy scales (OR = 0.12 95% CI: 0.024–0.56). Conclusions: Further studies are needed to confirm the prevalence of transcriptionally active HPV infections in pituitary adenomas and the role of these infections in the invasiveness of pituitary tumors.