In our recently published article,10 we reported results of a multi-institutional database on PSCC patients who underwent inguinal lymph node dissection (ILND), evaluating whether the presence of HPV infection could be a predictor of response to perioperative RT. Patients with HPV+ PSCC had a lower burden of inguinal lymph node metastases (ILNM), identified both as pathologic N stage (p < 0.001) and ILNM density (p < 0.001), as compared to HPV-negative patients. Moreover, despite we found a similar overall survival (OS) rate between HPV+ and HPV– patients regardless of adjuvant treatment used, the restricted mean survival time (RMST) analyses showed an OS benefit for HPV+ patients at 3 yr (3.5 mo, 95% confidence interval [CI] 1.6–5.3; p < 0.001), 5 yr (7.2 mo, 95% CI 3.0–11.4; p = 0.001), and 7 yr (9.7 mo, 95% CI 2.1–16.6; p = 0.006), without significant differences at 10 yr (8.3 mo, 95% CI –3.7 to 20.2; p = 0.2). Conversely, when considering only patients treated with perioperative RT, HPV+ status was associated with longer median OS (p = 0.015) and longer RMST at 3 yr (9.5 mo, 95% CI 5.7– 13.2; p < 0.001), 5 yr (23.3 mo, 95% CI 15.5–31.1; p < 0.001), 7 yr (32.3 mo, 95% CI 17.8–46.9; p < 0.001), and 10 yr (39.1 mo, 95% CI 11.8–66.4; p = 0.005) of follow-up. In order to understand the biology underlying these different responses a comprehensive genomic profiling (CGP) assay on tumor tissues was carried out. Particularly, PI3KCA was the most common altered gene in HPV+ patients (38.7% vs. 17%) followed by KMT2D (25.8% vs 3%), while TP53 (75.2% vs. 15%), CDKN2A (65% vs 1%), and TERT (promoter region; 60.2% vs 9%) were mostly altered in HPV-negative tumor. Moreover, the median tumor mutation burden (TMB) was higher in HPV+ than in HPV– tumors (5.2 mutations/Mb vs. 3.2 mutations/Mb).
Despite we were unable to separately analyze the impact of preoperative and postoperative treatments and the lack of information regarding the use and type of adjuvant chemo-sensitizing agents used as well as the fields for RT treatment, we identified a novel tumor-related factor for the selection of the most suitable candidates for multidisciplinary treatment after surgery. Particularly, we provided results suggesting that the higher TMB and the lower TP53 mutation frequency for HPV+ tumors could have a role in PSCC sensitivity to perioperative RT. Finally, the latter feature could be introduced as a tool to stratify patients in randomized clinical trials.
Written by: Giuseppe Basile,1 Marco Bandini,1 Philippe E. Spiess2 and Andrea Necchi1,3
- San Raffaele Hospital and Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy;
- Moffitt Cancer Center and Research Institute, Tampa, FL, USA
- Fondazione IRCCS Istituto Nazionale dei Tumori
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