ESMO Virtual Congress 2020: Association Between Human Papillomavirus Infection and Outcome of Perioperative Nodal Radiotherapy for Penile Carcinoma

( The overall incidence of human papillomavirus (HPV) DNA in penile cancer is 42-70%, which is lower than cervical carcinoma (~100%), and similar to vulvar carcinoma (~50%). HPV prevalence differs by histologic subtype in penile cancer, including 100% of the ‘warty’ subtype, 80% for basaloid, 34.9% for keratinizing squamous cell carcinoma, and 33% of verrucous carcinoma. However, data related to the impact of HPV infection status and the outcome of perioperative treatments in patients with lymph node-involved penile squamous-cell carcinoma are lacking. At the virtual European Society of Medical Oncology – (ESMO) 2020 annual meeting, Dr. Andrea Necchi and colleagues reported results of their study analyzing the benefit of perioperative radiotherapy according to HPV infection status.

Within an international, multicenter database of 1,254 patients with penile squamous-cell carcinoma who received inguinal lymph node dissection from Europe, United States, Brazil, United Kingdom and China, 507 had suitable clinical information:


Kaplan-Meier and restricted mean survival time examined the overall survival differences among HPV+ and HPV- patients according to the use of perioperative radiotherapy to involved regional lymph nodes. The analyses were also made after propensity score-matching (n=136). The authors also looked at the genomic alterations landscape of penile squamous-cell carcinoma from the Foundation Medicine database (N=199) to characterize HPV+ penile squamous cell carcinoma.

In this study, patients with HPV+ penile squamous-cell carcinoma exhibited a lower clinical N-stage (p<0.001) and inguinal lymph node metastasis density (p<0.001). HPV+ patients had similar median overall survival (p=0.1) but longer restricted mean survival time than HPV- patients at different time-points:


Nevertheless, HPV+ patients treated with perioperative radiotherapy exhibited longer median overall survival (p=0.015) and longer restricted mean survival time compared to HPV- patients:


These findings were not confirmed with perioperative chemotherapy (p=0.19). In the propensity-score matched cohorts, HPV+ status remained significantly associated with longer overall survival after radiotherapy. In multivariable Cox regression analyses, patients with HPV+ penile squamous-cell carcinoma exhibited a significantly improved overall compared with those with HPV- penile squamous-cell carcinoma (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%). There was one HPV+ patient with MSI-high status, and the median tumor mutation burden was 5.2 mutations/Mb (IQR 2.7-10.3), with 27% of cases with tumor mutational burden ≥10 mutations/Mb and 13% of cases with ≥20 mutations/Mb. There was one HPV- patient with MSI-high status, and the median tumor mutation burden was 3.2 mutations/Mb (IQR 1.7-5.2), with 10% of cases with tumor mutational burden ≥10 mutations/Mb and 2% of cases with ≥20 mutations/Mb.


Dr. Necchi concluded this presentation with the following summary points:

  • Using two large datasets of clinical and genomic data on patients with penile squamous cell carcinoma, the results suggest a potential role of perioperative radiotherapy for HPV+ penile squamous-cell carcinoma with lymph node involvement, mainly in the adjuvant setting
  • HPV+ tumors had a lower TP53 and CDKN2A mutations compared to HPV- tumors, which may justify in part their radiosensitivity
  • The latter feature may be employed as a stratifying biomarker within prospective randomized clinical trials

Presented by: Andrea Necchi, MD Medical Oncologist, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the European Society for Medical Oncology Virtual Congress, ESMO Virtual Congress 2020 #ESMO20, 18 Sept - 21 Sept 2020 

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