Objective
The objective of the study was to evaluate the risk of anal squamous intraepithelial lesions (ASILs) in immunocompetent women with genital squamous intraepithelial lesions (GSILs).
Study Design
This was a cross-sectional study that included 260 immunocompetent women divided into 2 study groups: 1 group included 184 women diagnosed with GSIL by genital colposcopy and biopsy, and the other included 76 controls. All subjects were submitted to anoscopy followed by a biopsy if pertinent.
Results
Of 184 GSIL women, 32 (17.4%) had ASIL ( P < .001). The risk of ASIL was 13.1 times greater for GSIL women when there were 3 or 4 genital sites involved. All cases of high-grade ASIL were found in women with cervical GSILs. Among risk factors, anal intercourse without a condom demonstrated an important association with ASIL (prevalence ratio adjusted for age = 2.6).
Conclusion
There seems to be a strong association between ASIL and multicentric GSIL. Another factor related to ASIL was the practice of unprotected anal intercourse.
Cervical squamous intraepithelial lesions are associated with the human papillomavirus (HPV), and the characteristics and morphology of these lesions have been extensively studied. However, others sites can be infected by the virus, resulting in squamous intraepithelial lesions (SILs) of the vagina, vulva, and perianal region. Recently research has focused on intraanal sites, but there has not been any distinction made between endoanal SILs and perianal SILs. The classification is based on histopathological findings, but the prognosis and evolution of each disease are likely different if the lesions are found on the mucosa vs on the skin.
Many authors have described the similarities between cervical uterine and anal canal carcinogenesis, and an association between anal squamous intraepithelial lesions (ASILs) and a history of cervical SILs or an abnormal Papanicolaou smear has been observed. Scholefield et al (1992) reported a higher ASIL prevalence in patients with cervical, vaginal, and vulvar SILs. However, a history of vulvar SILs might be a risk factor for ASIL, demonstrating the inherent multicentricity of anogenital SIL lesions that are related to HPV.
The lack of uniform terminology leads to the impossibility of estimating the prevalence of ASILs and perianal SILs. It should be noted that perianal SILs, like vulvar SILs, are nonhairy skin lesions. Thus, the lesions are grouped into 2 major carcinogenic types: one related to HPV and its cofactors, which account for 30–50% of cases, and the other related to dermatological lesions, in which hyperplastic lichen sclerosus predominates.
Endoanal cancer and perianal cancer were considered rare until the 1970s, when a 1.5:1 women/men ratio was observed. There were many changes in this pattern between 1977 and 1986, with a significant increase of reported cases, especially among homosexual and bisexual men. The practice of receptive anal sex increases the incidence of anal cancer 25- to 50-fold among these groups when compared with heterosexual men. Nevertheless, receptive anal intercourse does not seem to be the only factor related to anal carcinogenesis. A history of HPV infection (especially high-risk types such as 16 and 18), human immunodeficiency virus (HIV) seropositivity, HSV (herpes simplex virus) infection, smoking, and chronic anal irritation that leads to fissures and fistulas are other associated risk factors.
Frisch et al (1997) observed that the incidence of anal cancer has been increasing over the last few decades, especially in women. A multivariate analysis revealed a strong association between unprotected sexual intercourse and anal cancer in both sexes. In addition, a history of anal intercourse at young age, early history of anal intercourse and sexually transmitted diseases were linked to a higher risk of anal cancer in females.
Some questions need to be answered regarding the natural history of HPV-induced anal cancer among men and women. The majority of studies have focused on homosexual and bisexual men, thereby ignoring the cultural variety with respect to anal intercourse by women, which is an important factor related to anal carcinogenesis.
The objective of this study was to determine whether the risk of ASIL is related to the location and number of genital intraepithelial lesions.
Materials and Methods
This was a cross-sectional study of 260 HIV-negative women (using enzyme-linked immunosorbent assay [ELISA] and Western blot) presenting to the Hospital dos Servidores of Rio de Janeiro–Brazil between November 2003 and December 2004. The cases were separated into 2 groups. The first group of women had SILs of the cervix, vagina, vulva, and/or perianal area diagnosed by genitoscopy and biopsy, and the second group of women presenting for cervical cancer screening that had no SILs, as diagnosed by cytology (2 negative Papanicolaou smears) and a negative genitoscopy. The Papanicolaou tests and biopsies were reviewed by an expert pathologist. All patients participated in the study after providing oral and written informed consent.
The sample size calculation was based on an approximation of the expected prevalence probabilities for both groups with a P < .05 significance level. Using the limitation of 0.10 for the distance between a real and estimated prevalence, we anticipated that our results would reach significance with n ≥100 for the study group (n = 184) and n ≥60 (n = 76) for the control group based on the results from Holly et al (2001), who reported an ASIL prevalence of 8% in HIV-negative women (n = 68) with or without genital squamous intraepithelial lesions (GSILs).
Sociodemographic data for the studied women were taken from the medical history by one of the researchers. These data included the following factors: illicit drugs abuse; history of other sexually transmitted diseases (STD); use of immunosuppressor drugs; a history of hepatitis B and C; references to chronic degenerative diseases; anal illness such as fissures, fistulas, polyps, and hemorrhoids; sexual habits; and tabagism. This study excluded bisedes HIV-positive women; users of immunosuppressant medications, cocaine, or intravenous drugs; and those with chronic degenerative diseases.
All cases underwent an anogenital exam that included perianoscopy, vulvoscopy, colposcopy (genitoscopy), and anoscopy with magnified images. The examinations were completed by an expert colposcopist, with more than 30 years of practice, using a DF Vasconcellos colposcope (Sao Paulo, Brazil) with 5 levels of magnification. All suspicious lesions were biopsied.
The anal canal examination was assessed by anoscopy with colposcopic-magnified images of ×16–25 using 2% acetic acid solution, performed in a similar fashion to a cervical colposcopy. Biopsies were performed for all abnormal findings with Medina biopsy tweezers (3–5 mm tip). Fragments were fixed with 10% formol solution in separate containers according to the site of biopsy for hematoxylin-eosin staining and were examined by an experienced pathologist. Histological results were classified as normal; low-grade anal intraepithelial lesion (LG-ASIL) when atypical cells were limited to one third of the lower epithelium; and high-grade anal intraepithelial lesion (HG-ASIL) when atypia reached two thirds or more of the epithelium thickness.
Statistical analysis with 95% confidence intervals was used for prevalence calculations. The χ 2 and Fisher’s exact independent and homogeneous tests were applied. Age was adjusted by stratification of the subjects into 2 groups, using a cutoff of 40 years old. A probability of approximately 0.05 was adopted for the bivariate analysis of the contingency tables, and multiple logistic regression was used to eliminate confounding variables.
This study was approved by the Ethics Research Committee of the institution (Hospital of Servidores–Rio de Janeiro–Brazil).
Results
Of the 260 women studied, 184 presented with genital SILs (GSILs) (cervical, vaginal, vulvar, and/or perianal SILs), and 76 had no GSIL. Racial and sociodemographic features, except for age, education level, and contraceptive method used (adjusted for stratification by age with a cutoff between groups of 40 years old), were similar ( P = .683) ( Table 1 ).
