Introduction:

Organ-sparing surgery (OSS) for penile squamous cell carcinoma (PSCC) is the preferred treatment option for low-grade/low-stage tumors because despite higher recurrence rates, there is no impact on overall survival. Identifying factors associated with improved recurrence or survival can enhance personalized treatment options and improve outcomes. In this study, we examined the oncological outcomes of HPV-positive compared to HPV-negative PSCC at a single institution.

Methods:

A retrospective analysis of patients with penile cancer (Ta, Tis, T1-3) treated with low-risk OSS from May 2013 to May 2024 was performed. Low-risk OSS was defined as wide local excision, circumcision, Mohs micrographic surgery, laser ablation, cryotherapy, partial glansectomy, and glans resurfacing. Patients who had total glansectomy, partial penectomy, or total penectomy at primary surgery, or who had nodal disease or metastasis at presentation, were excluded. P16 immunostaining and in situ hybridization of resected tissue were primarily used together to determine HPV status, with PCR done in 1 case. 

Baseline characteristics were compared using independent t-test for continuous variables and Chi-square for categorical. HPV status in relation to recurrence and mortality was analyzed using Chi-square and Fisher’s exact test.

Results:

43 patients met study criteria, with the majority being HPV-positive (n=36, 83.7%). A total of 15 local recurrences, 7 regional recurrences, and 5 distant metastatic recurrences were recorded between the two groups. Baseline demographics and clinicopathologic characteristics were statistically insignificant between the two groups except for histologic subtype (Table 1).

HPV-negative patients were noted to have higher rates of local recurrence (71.4% vs 27.8%, P=0.04) and distant metastatic recurrence (42.9% vs 5.6%, P=0.024) compared to HPV-positive patients. No significant difference was noted in overall or regional recurrence based on HPV status. HPV-negative status was associated with higher cancer-specific mortality compared to HPV-positive patients (42.9% vs 2.8%, P=0.01) (Table 2). 

Conclusion:

HPV-positive PSCC is associated with significantly lower rates of both local and distant metastatic recurrence, as well as lower cancer-specific mortality on univariate analysis. Overall recurrences likely weren't statistically significant due to low statistical power. Our data shows that low-risk OSS may have higher efficacy for HPV-positive tumors and suggests the potential for a tailored approach to the management of localized penile cancer that maximizes quality of life without compromising oncological outcomes.

Funding: N/A