Association of P53 and P16 expression with surgical and oncologic outcomes in vulvar squamous cell carcinoma: a retrospective cohort study

The aim of this research is to evaluate the relationship between p53 and p16 expression and various clinicopathologic features, surgical interventions, and oncologic outcomes in patients diagnosed with vulvar squamous cell carcinoma (VSCC). We carried out a retrospective cohort study involving women treated for vulvar squamous cell carcinoma (FIGO stages I–IV) at Hôtel-Dieu de France in Beirut, Lebanon, from 2014 to 2024. Collected data included patient characteristics, surgical management, postoperative complications, pathological features, recurrence, and survival rates. Tumor specimens were analyzed for p53 and p16 expression using immunohistochemistry, and human papillomavirus (HPV) DNA was evaluated by vaginal PCR. Statistical analyses included Chi-square, Fisher’s exact, and Mann–Whitney tests, with significance set at p < 0.05. A cohort of 125 patients was initially included in the analysis, of whom 86 underwent p53/p16 immunohistochemical evaluation: 38 were p53-positive, 15 were p16-positive, 33 were p53/p16-negative,14 out of 86 patients were HPV positive. In the p53-positive group, tumors were more often central, resulting in clitoral excision in all patients in this subgroup ( p = 0.008). P53 positivity was associated with increased rates of inguinal lymph node metastasis ( p < 0.001) and a higher number of metastatic lymph nodes excised ( p = 0.001), and worse baseline Eastern Cooperative Oncology Group (ECOG) performance score ( p = 0.04). Although depth of invasion tended to be greater in p53-positive tumors, this difference was not statistically significant. Postoperative complication rates, recurrence, and survival were comparable across biomarker groups. No significant association was observed between p16 expression, HPV status, or smoking history. In our cohort, p53-positive vulvar squamous cell carcinoma was associated with more aggressive clinicopathologic features, including increased nodal involvement and wider surgical resection due to midline tumor location. However, p53 expression was not associated with higher postoperative complication or recurrence rates. These findings suggest that while p53 may reflect tumor aggressiveness; its role in guiding surgical or prognostic decision-making requires further prospective evaluation.