Human Papillomavirus (HPV)-Associated Primary Squamous Cell Carcinoma of the Rectosigmoid Colon: A Case Report and Literature Review of a Rare Malignancy

Primary colonic squamous cell carcinoma (SCC) represents a small minority of all colorectal cancer cases. Common clinical presentations include abdominal pain, weight loss, anorexia, dyschezia, and hematochezia. While adjuvant chemotherapy/radiation may be considered, treatment of colonic SCC is primarily surgical. We report a case of primary colonic SCC. A 66-year-old man with multiple comorbidities and a 42-pack-year smoking history presented with abdominal pain, constipation, and rectal bleeding. Colonoscopy findings included an anorectal ulcer and an ulcerated rectal mass, diagnosed as poorly differentiated, HPV-related SCC. Surgical treatment consisted of a low anterior resection with ileostomy and adjuvant chemoradiation, complicated by leukopenia/neutropenia. The ileostomy was reversed six months later with no gross malignancy. However, circulating tumor DNA (ctDNA) remained positive with a follow-up positron emission tomography scan and biopsy confirming recurrent SCC. The patient is currently receiving combination chemotherapy with carboplatin and paclitaxel, with considerations being made for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. This case demonstrates the role of ctDNA as an early marker of recurrence and an association with HPV infection. However, the risk factors for primary colonic SCC remain unclear, and adjuvant chemoradiation lacks consensus. Further evaluation of primary colonic SCC cases is necessary to determine standardized management guidelines.