Data related to the impact of human papillomavirus (HPV) infection status and the outcome of perioperative treatments in patients with lymph node-involved penile squamous-cell carcinoma (PSCC) are lacking. We aimed to analyze the benefit from perioperative radiotherapy (RT) according to HPV infection status.
Within an international, multicenter database of 1,254 patients (pts) with PSCC who received inguinal lymph node dissection (ILND) from Europe, United States, Brazil, United Kingdom and China, 507 had suitable clinical information. Kaplan-Meier and restricted mean survival time (RMST) examined the overall survival (OS) differences among HPV+ and HPV- patients according to the use of perioperative RT to involved regional lymph nodes. The analyses were also made after propensity score-matching (PSM; N=136). Multivariable Cox regression analyses for OS were also done. Finally, we looked at the genomic alterations landscape of PSCC from the Foundation Medicine database (N=199) to characterize HPV+ PSCC.
Pts with HPV+ PSCC exhibited a lower clinical N-stage (p<0.001) and ILNM density (p<0.001). HPV+ patients had similar median OS (p=0.1) but longer RMST than HPV- patients at different time-points. Nevertheless, HPV+ patients treated with perioperative RT exhibited longer median OS (p=0.015) and longer RMST compared to HPV- pts. These findings were not confirmed with perioperative chemotherapy (p=0.19). In the PSM cohorts, HPV+ status remained significantly associated with longer OS after RT. In multivariable Cox regression analyses, pts with HPV+ PSCC exhibited a significantly improved OS compared with those with HPV- PSCC (HR: 0.12, 95%CI: 0.03-0.48; p=0.003). Among the several different genomic alterations frequencies, the top-altered genes (>20%) in HPV+ cases were PI3KCA (38.7%) and KMT2D(25.8%), whereas in HPV- cases these were TP53 (75.2%), CDKN2A (65%) and TERT (promoter region, 60.2%).
Perioperative RT was more effective in the subgroup of HPV+ PSCC. Reasons for enhanced RTsensitivity may also be related to the different landscape of genomic alterations. These results should be considered as hypothesis-generating and may inspire future prospective trials.
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All authors have declared no conflicts of interest.