Human Papillomavirus–Related Rectal Squamous Cell Carcinoma in a Patient With Ulcerative Colitis Diagnosed on Narrow-Band Imaging


A 57-year-old woman presented with an 8-year history of chronic ulcerative colitis (CUC). She had received treatment with prednisone, and was maintained in clinical remission with 6-mercaptopurine. She subsequently developed steroid refractory symptoms and hence was given infliximab. Surveillance colonoscopy revealed a subtle erythematous flat lesion in the distal rectum, not contiguous with the dentate line (Figure A). Examination with narrow-band imaging (NBI) revealed a depressed lesion with an irregular ulcerated border, loss of the normal mucosal pit-pattern, and microvasculature (Figure B). Biopsy specimens from the lesion were consistent with squamous cell carcinoma (SCC) (Figure C), with strongly positive P16 immunostain consistent with human papillomavirus (HPV)-related dysplasia (Figure D). The patient was scheduled for rectal examination under anesthesia, with biopsy mapping of the distal rectal mucosa to determine management options.


Primary SCC accounts for only 0.025% to 0.1% of all colorectal cancers.1 We report a case of HPV-related rectal SCC in a patient with CUC, on chronic immunomodulator therapy, which was diagnosed using NBI, a new endoscopic technique for improved visualization of mucosal surfaces and capillary networks.

The presence of squamous epithelium in the colon/rectum is presumed to be the result of the following:1,2 (1) proliferation of uncommitted reserve or basal cells after mucosal injury; (2) squamous metaplasia of colorectal mucosa as a result of chronic irritation; (3) squamous metaplasia within a colorectal adenoma or adenocarcinoma; (4) malignant change in persistent ectopic embryonal nests of ectodermal cells; and (5) transitional-cell anal ducts that can extend cephalad beneath the rectal mucosa.

The role of HPV in the etiology of primary colorectal SCC has not been well defined. It has been hypothesized that chronic inflammation in CUC leads to squamous metaplasia and secondary infection with HPV leads to development of SCC.1 Because squamous metaplasia often involves the distal 2 to 4 cm of the rectum as a continuous extension from the dentate line, it has been speculated that this location forms a transition zone, similar to the cervical transformation zone, and hence is at comparable risk for HPV infection and SCC.3

The use of NBI facilitated the diagnosis of rectal SCC in this patient. It allowed improved characterization of the depressed lesion and differentiation from the surrounding normalappearing mucosa. The incorporation of mucosal imaging techniques (chromoendoscopy and NBI) in CUC surveillance may facilitate targeted biopsies of abnormal lesions, thereby resulting in an increase in the early diagnosis of dysplastic and malignant lesions of the colorectum in this high-risk population.


  1. Kong CS, Welton ML, Longacre TA. Role of human papillomavirus in squamous cell metaplasia-dysplasia-carcinoma of the rectum. Am J Surg Pathol 2007;31:919–925.
  2. Sotlar K, Koveker G, Aepinus C, et al. Human papillomavirus type 16-associated primary squamous cell carcinoma of the rectum. Gastroenterology 2001;120:988–994.
  3. Welton ML, Sharkey FE, Kahlenberg MS. The etiology and epidemiology of anal cancer. Surg Oncol Clin N Am 2004;13:263–275.