Significance of HPV status on tumor response and treatment outcomes in endocervical adenocarcinoma treated with definitive chemoradiotherapy: a retrospective study

Objective: We aimed to compare tumor response and treatment outcomes between human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) endocervical adenocarcinomas (ADCs) treated with definitive concurrent chemoradiotherapy (CCRT) and to identify prognostic factors. Methods: We conducted a retrospective review of 40 patients with endocervical ADCs treated with definitive CCRT (stages I–IVA) between 2011 and 2022. Based on pathological review the cases were categorized as HPVA or HPVI ADCs. Statistical analyses were performed to compare the characteristics, complete response (CR) rates, and survival outcomes. Results: Of 40 patients, 22 (55.0%) had HPVA and 18 (45.0%) had HPVI ADCs. HPVI patients had significantly higher rates of parametrial invasion (94.4% vs. 45.5%, p=0.001). CR was achieved in 57.5% of patients and was significantly more common in the HPVA group (81.8% vs. 27.8%, p=0.001). Patients with HPVI had higher recurrence rates (88.9% vs. 50.0%, p=0.016) and lower 3-year progression-free survival (PFS, 16.7% vs. 49.8%, p=0.001), distant metastasis-free survival (DMFS, 38.1% vs. 80.8%, p=0.001), and overall survival (OS, 42.3% vs. 90.7%, p=0.002) rates. HPVA remained a significant factor for PFS (hazard ratio [HR]=3.44; 95% confidence interval [CI]=1.09–10.81; p=0.035) and OS rates (HR=6.83; 95% CI=1.17–39.80; p=0.033) in multivariate analysis. Conclusion: HPVI ADC was associated with a lower response to definitive CCRT and worse prognosis than HPVA ADC. These findings suggest the need for tailored treatment strategies based on the HPV status.