Perianal squamous cell carcinoma in-situ: a report of two human papilloma virus-negative cases
© Shehan et al; licensee BioMed Central Ltd. 2008
Received: 08 August 2008
Accepted: 20 August 2008
Published: 20 August 2008
We are reporting two cases of perianal squamous cell carcinoma in-situ, negative for high-risk (HR) and low-risk (LR) human papilloma viruses. A brief review of anal and perianal squamous cell carcinoma and the role of HPV are presented.
Squamous cell carcinoma, the second most common form of skin cancer, most often affects sun-exposed surfaces. However, squamous cell carcinoma can involve skin surfaces not previously exposed to sunlight, such as in the anal and perianal regions. Invasive perianal squamous cell carcinoma is a locally infiltrative malignant skin tumor that exhibits destructive growth. It is a relatively uncommon tumor, which develops from the precursor lesion anal intraepithelial neoplasia (AIN). Immunosuppression is felt to be a risk factor.
Fluorescent in-situ hybridization (FISH) for high- and low-risk HPV was performed on formalin fixed, paraffin embedded tissue from each case. Both cases were negative for both categories of HPV.
Squamous cell carcinoma tends to develop on previously damaged skin, such as that injured by sun exposure. Immunosuppression is considered a risk factor in tumor development. Anal intraepithelial neoplasia (AIN) is a precursor lesion to invasive squamous cell carcinoma in much the same way as cervical intraepithelial neoplasia (CIN) precludes invasive carcinoma of the cervix. HPV is important in the pathogenesis of lesions in both of these sites.
More than 100 types of HPV have been reported to date. Of these, 30 infect the anogenital area. Genital HPV infection is common and usually self-limited with few, if any, symptoms. Condylomas, benign proliferative lesions, when they do occur, affect men and women and can be found on the uterine cervix; these lesions are usually associated with low-risk HPV types 6 or 11. Other HPV types that infect the anogenital region, such as high-risk types 16, 18, 31, 33, and 35, are all strongly associated with CIN. In fact, persistent infection with high-risk types of HPV is the most important risk factor for CIN and invasive carcinoma. HPV type 16 is the type most often associated with this process. Similarly, up to one-third of anal squamous cell carcinomas appear to be associated with HPV infection. Bjørge , in a large case-cohort study, found that patients seropositive for HPV's 16 and 18 had an increased risk of developing anal and perianal skin cancer. Perianal Bowen's disease, in particular, was associated with high risk HPV positivity [2, 3].
Not all perianal squamous cell carcinoma or condylomas are associated with HPV infection, however. Frisch  showed fewer perianal skin cancers associated with high-risk HPV when compared to cervical and vulvar carcinomas, suggesting that in some cases, particularly in elderly patients, a causal pathway independent of HPV is present. Tachezy in a series of 10 anal condylomas, found 3 to be HPV negative. Even in one of our cases, there is clear evidence of perianal condyloma acuminatum. Smoking is suggested as one risk factor that may be operative in such HPV negative cases of anal carcinoma, affecting premenopausal women more than postmenopausal women [6, 7].
In our cases, we speculated that other causes such as smoking, other genital infections, or unknown factors play a role in the development of squamous cell carcinoma.
Written consent was obtained from the patients for publication of this report. A copy of the written consent is available for review by the Editor-in Chief of this journal.
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