Human papillomavirus infection in metastatic lung adenocarcinoma is associated with better outcomes with immune checkpoint inhibitor treatment.

Abstract

e21569 Background: Human papilloma virus (HPV) is associated with the development of several primary tumors. Recent studies have shown that HPV-positive tumors tend to be sensitive to immune checkpoint inhibitors (ICI), owing to the presence of xenobiotic genomes in cancer cells. The objective of this study was to explore this relationship in patients with lung adenocarcinoma. Methods: A retrospective cohort analysis in patients with advanced lung adenocarcinoma treated in a reference center in Bogota, Colombia was conducted. Demographic as well as treatment variables were collected between January 2018 and December 2019. Besides clinical outcomes, HPV infection status was determined by PCR amplification and reverse line hybridization directly on formalin-fixed paraffin-embedded tumor samples. Statistical analyses included stratified survival analysis based on HPV status and response. Results: A total of 133 patients were included. Male predominance (51.1%) with Karnofsky performance scores (KPS) greater than 80, and 19% of prior cigarette exposure (26 patients) was identified in the cohort. HPV positivity was identified in 25.6% of patients (33 cases, [95%CI 17.5-32.2%]), in addition to 29.8% EGFR mutation positivity (29 cases [[95%CI 14.8-28.8%]), 6% ALK positivity (8 cases [95%CI 1.9-10]) and positive PD-L1 expression in 49 samples (36.8% [95%CI 28.6-45%]). In immune checkpoint inhibitor (ICI) exposed patients, HPV+ patients had significantly higher PD-L1 expression compared with HPV- individuals (p < 0.001). In terms of overall survival, ICI treated patients achieved an OS of 27.1 months (95%CI 22.1-NA) and a PFS of 19.4 months (95%CI 18-24.5 months). HPV infection status was associated with prolonged OS (median OS not reached, [95%CI 27.7 months – no reached], p = 0.0089) and better response to ICI (p < 0.001). Conclusions: HPV infection is prevalent in patients with lung adenocarcinoma and is associated with better response to ICIs as well as better survival outcomes. Its identification could serve as a prognostic marker, especially in female non-smoker patients.