Unveiling the rare: p16 expression and real-world management of penile cancer in Bolivia—Insights from a country with high HPV and penile cancer prevalence.

6 Background: Penile squamous cell carcinoma (PSCC) is rare but a major challenge in regions with high human papillomavirus (HPV) prevalence. Bolivia ranks among South American countries with the highest HPV infection and penile cancer rates, yet no molecular or outcome data have been published. This study presents the first Bolivian real-world cohort evaluating p16 expression, clinicopathologic features, and outcomes. Methods: Cross-sectional, ambispective (retrospective–prospective) observational study of patients with PSCC treated at the Instituto Oncológico del Oriente Boliviano (2018–2025). Fifty-three patients were included. Demographic, clinical, and histologic data (Cubilla prognostic index, p16 IHC) were reviewed, as well as treatments and responses. Results: Median age was 59 years. Phimosis occurred in 18.9%, and 22.7% had premalignant lesions. p16 positivity was found in 43.4%. No HIV-positive patients were identified. The glans was the predominant site (47.2%), followed by glans–prepuce (22.6%). Grades were mainly G2 (66%) and G1 (32.1%). Subtypes included keratinizing (24.5%) and conventional squamous (28.3%). Lymphovascular invasion appeared in 39.6%, perineural in 21%, and lymphocytic infiltrate in 28%. According to Cubilla index, 71.7% were high-risk. Stage IV disease predominated (37.7%). Surgery was performed in 51 patients: 22.6% total penectomy with bilateral lymphadenectomy, 7.5% penectomy alone, and 5.7% with orchiectomy. Complications were rare (infection 3.8%). Neoadjuvant chemotherapy was given only to 9.4%, adjuvant to 28.3%, and radiotherapy to 21%. Conclusions: This first national series shows high HPV-related (p16+) penile cancer prevalence (43.4%), comparable to Brazilian/Paraguayan data (40–50%), slightly higher than Argentinian reports (~35%), and well above North American and European data (20–30%). Most patients presented with locally advanced disease, reflecting diagnostic delay. These data supported the 2024 introduction of male HPV vaccination in Bolivia and the creation of the IOOB Uro-Oncology Tumor Board (2023), which standardized neoadjuvant chemotherapy use. Findings underscore the need to improve genital hygiene education, expand HPV vaccination, and train physicians for early detection of premalignant lesions and malignant tumors in this high-incidence region.