High human papillomavirus viral load and local immune dysregulation are associated with poor clinical outcomes in patients with cervical cancer

Objective Human papillomavirus (HPV) infection is the primary cause of cervical cancer. Higher viral load, i.e. a greater abundance of HPV DNA in a tumor, has been associated with poorer clinical outcomes, and may play a role more accurate prediction of (non-) responders to treatment. In this study, we investigated the correlation between HPV viral load, clinical outcomes, and immune parameters related to HPV infection. Methods HPV viral load was quantified using qPCR on biopsies from a prospective cohort of women diagnosed with cervical cancer. Patients were categorized into two HPV viral load groups based on the optimal fit of a non-linear piecewise regression model. Immunohistochemical staining was used to measure tumor cell characteristics (Ki67, p16 INK4a , Pan-CK), as well as local tumor immune parameters (CD3, CD4, CD8, FOXP3), and immune checkpoint expression (PD-1, PD-L1). Kaplan-Meier curves were generated to compare recurrence-free and overall survival. Results Of the 44 women included in our study, high HPV viral load was significantly associated with shorter overall and recurrence-free survival ( p =0.045 and p =0.046, respectively; two-sided), and positively correlated with an increased risk of both lymph node and distant metastasis. In addition, a high HPV viral load was linked to lower percentages of tumor-infiltrating lymphocytes, and reduced expression levels of PD-1 and PD-L1. Conclusion The viral load of HPV in cervical cancer correlates positively to metastasis and recurrence, and negatively to survival rates, potentially due to local immune suppression. These results might indicate a lower response to ICI in the high viral load group, and that other treatment options should still be explored.