HPV is an essential driver in recurrence of cervical cancer

Introduction: High-risk human papillomavirus (HPV) has been detected in distant metastases from cervical cancer (CC) patients, suggesting a role of HPV. Material and methods: Here, we included 26 patients with recurrence of CC (2019-2023). With next generation sequencing (NGS) and immunohistochemical staining, primary and recurrent tissues were analyzed for HPV DNA and HPV RNA, p16 INK4a expression, and somatic TP53 and RB1 mutations. Results: All primary and corresponding recurrent tissues were HPV DNA and HPV RNA positive. Within the same tissue, we found complete DNA/RNA agreement in 25/26 (96.2 %) primary and 25/25 (100 %) recurrent tissues, and partial agreement in the remaining sample. There was complete agreement between primary and recurrent tissue in 23/26 (88.5 %) and 23/25 (92.0 %) patients on DNA and RNA, respectively, whereas the remaining showed partial agreement with two genotypes detected in primary and only one of these in recurrent tissue. Except for one sample, all samples from high-risk HPV-positive patients were p16 INK4a positive. The low-risk HPV11-positive patient was p16 INK4a negative and had a pathogenic TP53 mutation, while the remaining samples were TP53/RB1 mutation negative. Conclusion: In high-risk HPV-positive CC patients, HPV seems to play a role in recurrent disease. Our findings support ongoing research on targeting HPV oncogenes in CC, also in metastatic disease.