Abstract
Anal cancer is a rare malignancy with rising incidence, largely attributed to human papillomavirus (HPV) infection. Transgender women (TGW) are particularly vulnerable to HPV-related cancers due to higher rates of HPV acquisition, and gender-affirming surgeries, such as vaginoplasty, introduce unique anatomical challenges in management. We present the case of a 58-year-old TGW with a history of gender-affirming hormonal therapy and vaginoplasty using a bowel segment, who presented with anal symptoms and was diagnosed with well-differentiated, HPV p16-positive squamous cell carcinoma. Staging revealed a locally advanced tumor without metastasis. She underwent chemoradiation with mitomycin C (MMC) and 5-fluorouracil (5-FU), achieving an initial complete response, but positron emission tomography (PET) imaging a year later detected recurrence. A multidisciplinary team (MDT) recommended abdominoperineal resection (APR); however, intraoperative findings revealed a neovagina composed of sigmoid colon, precluding rectal resection alone, and the surgery was initially aborted. A month later, a combined APR with neovagina resection was performed, and pathology showed complete tumor response. The patient recovered well postoperatively. This case underscores the importance of obtaining detailed surgical histories and thoroughly reviewing preoperative imaging in transgender patients. Clinicians must be prepared for unexpected anatomical variations that require surgical adaptation and consider the psychosocial impact of neovaginal loss. Ultimately, comprehensive, multidisciplinary care is essential for optimizing the oncological and functional outcomes of transgender patients with anal cancer.