Anal intraepithelial neoplasia and invasive cancer of the anus
Anal intraepithelial neoplasia (AIN) is a potentially premalignant change found in the anal canal. It was considered rare disease and was a coincidental finding in 0.2-10.5% women with CIN. AIN is relatively recently recognized clinical problem and its prevalence is largely unknown as well as it malignant potential. The description and grading of the morphologic changes seen in both the cervix and the anal canal, histologically are very similar, differing only in the degree of keratinisation. Similar to other lower genital system neoplasia AIN is divided into three grades: AIN1, AIN 2 and AIN 3. AIN 1 and 2 are more often seen in younger patients, 19-43 (in average 26) years old, while AIN 3 is present in women older than 40 years.
Confirmations that HPV has an important role in the etiology of majority lower genital system cancers refer to perianal and anal region as well. It is pointed out that the transmission of HPV along genital system is by direct spread from adjacent areas. In this localization it will be from vulva to perianal and anal region. Today it is known that up to 20% of woman with CIN 3 have histology of AIN. Etiological association of HPV infection and anal cancer was reported 20 years ago. Both histologic and viral analyses confirm this association, HPV 16 being the type most frequently isolated. Except HPV 16 positivity, smoking is identified as the risk factor for AIN. Local trauma, Human immunodefficiency virus (HIV) and depressed immune function (such as in renal transplants) are potential cofactors.
Squamous carcinoma of the anus is an uncommon tumor that accounts for approximately 2% of cancers of the large bowel. It typically occurs in the elderly and previously used to be seen more frequently in women. However, there has been a striking incidence of this cancer in HIV positive young men. Over 28% women with anal squamous carcinoma have the history of genital warts in the past.
Compared to CIN where the progression is expected in 36% over period of 20 years, the natural history of perianal and anal intraepithelial neoplasia is not well understood. Anal carcinoma is less frequent than cervical cancer and rate of progression of AIN 3 to invasive cancer is surely lower.
Clinicaly the disease is similar to intraepithelial disease of the vulva in that it often shows pigmentation of the perianal and anal epithelium.
Perianal intraepithelial neoplasia occurs in two clinical forms:
as neoplastic transformation of macroscopic codylomata acuminata frequently unsuspected before the histologic examination and
as plaques of thickened, keratotic, often discolored perianal skin.
Although such lesions are generally visible to the naked eye, they are much better appreciated through the colposcope after the application of 5% acetic acid. Vascular shapes that are seen in cervix (punctations and mosaic) are not frequent on perianal area but may be found in anal canal.
Low grade AIN was characterized by mild to moderate aceto-white change on colposcopy. No abnormal vessel patterns were observed. Half of these were incorrectly predicted by colposcopy as SPI. High grade AIN in the anal canal is characterized by dense aceto-white change, sometimes occupying the full circumference.
AIN may be in continuity with vulvar disease, but also may appear as an isolated lesion in the absence of vulvar changes. Colposcopist must be aware of the nature of this disease and possible break in its continuity. The presence of perianal warts increase the chance for presence of intraepithelial lesions in anal canal. Over half of women with CIN and VIN have anal lesions associated with HPV 16. Therefore each women with HPV infection of vulva must be colposcopicaly examined in detail, including anus and perianal area because cytological confirmation for the existence of these lesions is difficult due to small number of cells obtained by cytological smear and their contamination with fecal contents.
It is difficult to distinguish early invasive lesions within high-grade AIN. Invasive cancer should be excluded. Irregular, dense aceto-white epithelium, within which lay a number of dilated irregular vessels.
Alarming rate of increase of ano-genital HPV infection in the sexually active population may herald a forthcoming dramatic increase in HPV associated cancers. If AIN 3 does carry significant invasive potential, an increase in the incidence of invasive anal squamous cell carcinoma may be expected.
