PD-L1 expression, DNA mismatch repair genes, and HPV types in cervical squamous cell carcinoma.

Abstract

5533 Background: Previous studies observed low PD-L1 expression in cervical cancer, and that high PD-L1 expression is associated with deficient DNA mismatch repair genes and poor prognosis. No study has investigated the PD-L1 expression differences among HPV types in cervical cancer. We aim to determine PD-L1 expression in our patient population and its clinical significance. Methods: A total of 198 patients with SCC were identified and 60 had evaluable tumor specimens and clinical data. Immunohistochemistry on MMR genes and PD-L1 expression using tissue microarrays was performed. HPV analysis for 15 high-risk types was done by multiplex PCR and gel electrophoresis. Correlation between PD-L1 expression, MMR status, HPV types and other clinical parameters was analyzed using χ2 or Fisher's exact test. Cumulative 5-year survival was analyzed by Kaplan-Meier curves and log rank test. Results: Of the 60 patients, 90% were black, 55% between ages of 30-55 and 40% older than 55. 33 patients had poorly, 20 moderately, and 7 well-differentiated tumors. At 5-year follow up, 11 had recurrence, 14 patients died of disease and 7 lost to follow up. 93.3% of tumors had positive staining for PD-L1 with 56.7% showing high expression. Patients aged 30-55 showed a higher rate of PD-L1 expression. Majority had intact MMR (91.7%). High-risk HPV DNA was extracted in 41 specimens (68.3%), 11 of these were infected with ≥2 or more types, identifying 6 high-risk types not included in vaccine. Correlation analysis showed that there is significant correlation between age and PD-L1 expression on tumor cells (p = 0.047). No correlation between MMR status and PD-L1 expression. Mean disease free survival (DFS) was 43.7, 36.5, and 6.3 months for high, low and negative PD-L1 expression, respectively (p = 0.002). In patients with stage I-II disease, mean DFS was 52.2, 42.6 and 7.6 months for high, low and negative PD-L1 expression, respectively (p = 0.001). Similar direct relationship is observed with overall survival. Cases with mixed HPV infection are associated with late clinical stage at diagnosis (p = 0.037) and lower PD-L1 expression. Conclusions: Contrary to previous studies, our results showed remarkably high rate of PD-L1 expression in cervical SCC, which is associated with longer DFS and OS, especially in early stage tumors. Mixed HPV infection is associated with late clinical stage at diagnosis and lower PD-L1 expression.