Herpetic reactivation during radiotherapy treatment for gynaecological cancers-a retrospective observational study

Herpes simplex virus (HSV) and varicella zoster virus (VZV) remain latent in sensory ganglia and can reactivate under immunosuppressive states such as cancer therapy. Radiotherapy-induced local immune suppression may increase the risk of herpes reactivation, leading to treatment interruptions and suboptimal outcomes. Evidence on the incidence and determinants of herpes reactivation among gynaecologic cancer patients undergoing radiotherapy remains limited.

A retrospective observational study was conducted at St. John's Medical College Hospital, including women ≥ 18 years with histologically confirmed gynaecologic malignancies treated with definitive or adjuvant radiotherapy between January 2016 and October 2025. Demographic, clinical, treatment-related characteristics, and comorbidities were analyzed. The study aimed to determine the incidence of HSV/VZV reactivation during radiotherapy, evaluate associated risk factors.

Among 391 patients analyzed, herpes reactivation occurred in 5.6% (22 patients). All reactivations occurred in patients with carcinoma of uterine cervix (7.6% (22/291); p = 0.018), with no HRA in other gynaecologic cancers. Higher EBRT dose (p = 0.020), use of VMAT/IMRT techniques (p = 0.008), concurrent chemotherapy (8.1% vs 0%, p = 0.002) and presence of STIs (Sexually Transmitted Infections) (27.8% (5/18) versus 4.6% (17/373); p < 0.001) were associated with significantly increased risk. Interestingly, the patients treated post COVID 19 pandemic were more likely to develop reactivation that those treated before pandemic (8.8% vs 1.7%; p = 0.002). 53.3% of the treatment interruptions were attributable to HRAs.

Herpes virus reactivation during radiotherapy for gynecologic cancers is a significant cause of treatment interruption. Carcinoma uterine cervix and presence of other STIs are significant risk factors. There is higher incidence of reactivations in the post COVID era.