Presence Of High-grade Squamous Intraepithelial Lesion Research Articles

Anal Dysplasia Screening and Treatment in a Southern Human Immunodeficiency Virus Clinic.

Persistent human papillomavirus infection in human immunodeficiency virus (HIV)-infected individuals has been strongly associated with anal squamous cell carcinoma. The incidence of anal squamous cell carcinoma continues to increase in this population despite advances in HIV therapy. There are few studies describing the prevalence of anal cancer precursors, treatment outcomes, and associated factors among HIV-infected populations in the southern United States. A retrospective chart review was performed on 355 HIV-infected patients from a Southern HIV clinic who were 18 years or older and had received at least one anal Pap smear. Demographic and clinical variables were collected. Descriptive statistics, single variable, and multivariate logistic regression analysis were performed to evaluate for predictors of high-grade squamous intraepithelial lesion (HSIL). Odds ratios and 95% confidence intervals were constructed for independent measures. After the first anal Pap smear, 38.3% (70/183) of patients with abnormal results were lost to follow-up. Comparing patients with biopsy proven HSIL versus low-grade squamous intraepithelial lesions, patients were less likely to have HSIL if they had a higher CD4 count (odds ratio, 0.81; 95% confidence interval, 0.72-0.93; P = 0.0022). Treatment success after the first round of treatment for topical and infrared coagulation therapy was 36.7% (18/49, all therapy types), and of those who achieved biopsy proven treatment success at follow-up screening, 94.4% (17/18) required subsequent therapy. Patients with a higher CD4 count were less likely to have HSIL. CD4 nadir, number of sexual partners, and race/ethnicity were not significantly associated with the presence of HSIL.

Human Papillomavirus Infection in HIV-1 Infected Women in Catalonia (Spain): Implications for Prevention of Cervical Cancer

BackgroundHigh-risk human Papillomavirus infection is a necessary factor for cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1-infected women, HPV infection is more prevalent and a higher risk of cervical cancer has been identified. We aimed to calculate the prevalence of infection by HR-HPV, determine the factors associated with this infection and abnormal cytology findings and to describe the history of cervical cancer screening in HIV-1-infected women.MethodsWe enrolled 479 HIV-1–infected women from the PISCIS cohort. Each patient underwent a gynecological check-up, PAP smear, HPV AND Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We applied questionnaires to obtain information on sociodemographic, behavioral, clinical, and cervical screening variables. We present a cross-sectional analysis.ResultsMedian age was 42 years. The prevalence of HR-HPV infection was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL) was 3.8%. The most common genotypes were 16(23%), 53(20.3%), and 52(16.2%). The factor associated with HR-HPV infection was age <30 years (odds ratio[OR],2.5; 95%confidence interval[CI],1.1–5.6). The factors associated with the presence of HSIL or low-grade squamous intraepithelial lesions (LSIL) were CD4T-lymphocyte count <200cells/mm3 versus >500cells/mm3 (OR,8.4; 95%CI,3.7–19.2), HIV-1 viral load >10,000copies/mL versus <400copies/mL (OR,2.1; 95%CI,1.0–4.4), and use of oral contraceptives (OR,2.0; 95%CI,1.0–3.9). Sixty percent of HIV-1–infected women had had one Pap smear within the last 2 years.ConclusionsThe high prevalence of HPV infection and cervical lesions in the HIV-1–infected population in Catalonia, as well as the low coverage and frequency of screening in this group, means that better preventive efforts are necessary and should include vaccination against HPV, better accessibility to screening programs, training of health care professionals, and specific health education for HIV-1–infected women.

Cervical cytological abnormalities and factors associated with high-grade squamous intraepithelial lesions among HIV-infected women from Rio de Janeiro, Brazil

Although cervical cancer remains a major public health problem in Brazil, knowledge of cervical cytological abnormalities among HIV-infected women remains scarce. At baseline evaluation of a cohort followed in Rio de Janeiro, Brazil, 703 HIV-infected women underwent cytology-based cervical cancer screening and human papillomavirus (HPV) DNA testing. Poisson regression analysis was used to evaluate the association of factors with the presence of high-grade squamous intraepithelial lesions (HSIL). Cervical cytology was abnormal in 24.3% of the women; 4.1% had HSIL. Beyond HPV infection, factors independently associated with the presence of HSIL was age (≥25 and ≤40 years, prevalence ratio [PR] 2.60, 95% confidence interval [CI] 1.11-6.10), and more than three pregnancies was protective (PR 0.33, 95% CI 0.11-0.94). High coverage of cervical cancer screening is warranted to prevent morbidity and mortality from cervical cancer in this population.

P16 and MIB1 improve the sensitivity and specificity of the diagnosis of high grade squamous intraepithelial lesions: Methodological issues in a report of 447 biopsies with consensus diagnosis and HPV HCII testing

Objective Many investigators are studying the additional value of biomarkers to improve histopathologic agreement, but few are using the same methodologies. Our objectives in this analysis to differentiate High-grade Squamous Intraepithelial lesions (HGSIL) from Low Grade Squamous Intraepithelial Lesions (LGSIL), atypia, and normal were: (1) to examine the rate of Human Papilloma Virus High-Risk positivity (HPV HR+), (2) to compare and grade the basal, parabasal, intermediate, and superficial layer staining of each marker, (3) to determine the optimal qualitative threshold for markers, (4) to compare p16 and MIB1 agreement, and (5) to examine the sensitivities and specificities using each markers alone and together. Methods A sample of biopsies from 208 patients were chosen from a total of 1850 patients and 3735 biopsies obtained during the course of ongoing optical trials. At least two independent blinded reviews were performed for each biopsy. A third review was performed if there was a disagreement between the two reviews. Both endocervical and ectocervical samples were stained for p16 and MIB1. A grading system that is delineated in the text ranged from 0 to 3 for both markers and each biopsy was scored by each cell layer. Frequencies, sensitivities, and specificities were calculated using Statistica. An ANOVA was used to compare p16 and MIB1 staining in the epithelial layers. Finally the sensitivity and specificity of each marker alone and together were examined. Results 453 specimens from 208 patients whose final diagnoses were normal ( n = 244), low-grade (LG) ( n = 59), and high-grade (HG) ( n = 144) were selected for analysis. 447 of 453 specimens were available for staining. Most LG and HG lesions were HPV HR positive. Endocervical samples stained positive less often than ectocervix and often results were discordant from ectocervical results. The analysis by layers showed pronounced increases in staining of both p16 and MIB1 as lesions progressed from normal to LG to HG. The cutoff or threshold for p16 was 0 versus 1–3 while for MIB1 it was 0–1 versus 2–3. Using the intermediate epithelial layer measurement of both p16 and MIB1 in HPV High-Risk Positive separated the normal tissue from LGSIL, normal from HGSIL, and LGSIL from HGSIL by a statistically significant margin ( p < 0.05). Each marker had sensitivities and specificities for the diagnosis of HGSIL versus LGSIL and normal of ∼ 85–90% and this improved by 5% for both sensitivity and specificity when used together (p16 sensitivity 90%, specificity 85%; MIB1 sensitivity 89%, specificity 87%; together sensitivity 94%, specificity 90%). Conclusion Several important methodological issues have been studied. Overall, p16 and MIB1 are promising markers to help pathologists differentiate HG lesions from all else. The staining of the endocervix and the ectocervix do not always agree, and the ectocervix more often stains positive with the presence of HGSIL. Each marker is helpful and both are helpful together. In conclusion, both markers are useful for the confirmation of HG lesions.

Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso

Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2–7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio (PR)=1.61, 95% confidence interval (CI): 1.4–1.8). High-risk HPV types (71 vs 40%, PR=1.79, 95% CI: 1.5–2.2), in particular HPV-16+18 (22 vs 9%, PR=2.35, 95% CI: 1.4–4.0), and multiple HPV infections (56 vs 23%, PR=2.45, 95% CI: 1.8–3.3) were more prevalent in HIV-1-infected women. High-grade SIL (HSIL) was identified in 3.8% of the women. Human immunodeficiency virus type 1 infection was strongly associated with presence of HSIL (adjusted odds ratio=17.0; 95% CI 2.2–134.1, P=0.007) after controlling for high-risk HPV infection and other risk factors for HSIL. Nine of 14 (63%) HSIL cases were associated with HPV-16 or HPV-18 infection, and might have been prevented by an effective HPV-16/18 vaccine.

Concurrent evaluation of visual, cytological and HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai, India.

Naked eye visual inspection with acetic acid (VIA), magnified VIA (VIAM), visual inspection with Lugol's iodine (VILI), cytology and human papillomavirus (HPV) testing were evaluated as screening methods for the detection of high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix in a cross-sectional study in Mumbai, India. Cytology, HPV testing, VIA, VIAM and VILI were carried out concurrently for 4039 women aged 30-65 years. All women were investigated with colposcopy and biopsies were taken from 939 women who had colposcopic abnormalities. The reference standard for final disease status was histology or negative colposcopy. The presence of HSIL was confirmed in 57 women (1.4%). The test characteristics for each method were calculated using standard formulae. The sensitivities of cytology, HPV testing, VIA, VIAM and VILI were 57.4%, 62.0%, 59.7%, 64.9%, and 75.4%, respectively (differences were not statistically significant). The specificities were 98.6%, 93.5%, 88.4%, 86.3%, and 84.3%, respectively. Adding a visual test to cytology or HPV testing in parallel combination resulted in a substantial increase in sensitivity, with a moderate decrease in specificity. The parallel combination of VILI and HPV testing resulted in a sensitivity of 92.0% and a specificity of 79.9%. As a single test, cytology had the best balance of sensitivity and specificity. Visual tests are promising in low-resource settings, such as India. The use of both VIA and VILI may be considered where good quality cytology or HPV testing are not feasible. The sensitivity of cytology and HPV testing increased significantly when combined with VIA or VILI.

Managing Atypical Squamous Cells of Undetermined Significance (ASCUS): Human Papillomavirus Testing, ASCUS Subtyping, or Follow-Up Cytology?

Colposcopically directed biopsy finds high-grade squamous intraepithelial lesion (HSIL) in the histologic specimen of 5% to 15% of cervical smears taken from women with a diagnosis of atypical squamous cells of undetermined significance (ASCUS). This study was designed to investigate the ability of human papillomavirus (HPV) testing, ASCUS subtyping, and follow-up cytology to predict the presence of HSIL in the cervical smear. The study material consisted of 918 liquid-based cervical cytologic samples (ThinPrep test, Cytec Corp, Boxborough, MA) collected in a single pathologic laboratory between 1997 and 2000. HPV testing was carried out in 704 of the samples that had sufficient cytologic material remaining for follow-up cytologic examination, including 105 with a normal diagnosis, 426 cases of ASCUS, 126 with low-grade squamous intraepithelial lesion (LSIL), and 47 with HSIL. The cervical samples of 91% of the women with HSIL, 88% of those with LSIL, and 49% of those with ASCUS were positive for all HPV types, but only 27% of those with normal cervical cytology contained all HPV types. When only high-risk HPV types were considered, the percentage of positivity for normal samples dropped to 19% and the percentage for HSIL increased to 96%. The ASCUS category was further sorted into ASCUS, favor reactive (AFR); ASCUS, not otherwise specified (ANOS); ASCUS, favor LSIL (AFLS); and ASCUS, favor HSIL (AFHS). Both high- and low-risk HPV types were found in AFR and ANOS samples slightly more frequently than in normal samples. High- and low-risk HPV types were found in AFLS far more frequently than in normal smears but slightly less than for LSIL. This pattern continued with the progression from LSIL to AFHS and from AFHS to HSIL. Three hundred eighty-six women of the 704 women had a year or more of follow-up data available, including a biopsy or other tests within 1 year of the cervical smear. Eight women with an initial diagnosis of ASCUS progressed to HSIL (3.4%). The presence of HPV was detected in the samples of all of these women, including high-risk HPV in seven of the eight, yielding a sensitivity of 88% and a specificity of 73% for high-risk HPV testing in predicting the development of HSIL in women with ASCUS. The positive predictive value for high-risk HPV testing was 11%. The sensitivity of any type HPV testing was 100%, but the specificity was only 48%. In all, 64% of the women for whom follow-up data were available regressed to normal. Compared with the 3.4% of ASCUS women who were found to have HSIL, 11% of the positive high-risk HPV patients developed HSIL. A designation of AFHS led to HSIL in 25% of the women with an initial diagnosis of ASCUS. Only 1.1% of the ASCUS women designated AFR later developed HSIL.

Human Papillomavirus DNA Detection in Cervical Specimens by Hybrid Capture: Correlation with Cytologic and Histologic Diagnoses of Squamous Intraepithelial Lesions of the Cervix

Human papillomavirus (HPV) DNA detection in cervical specimens was correlated with cytologic and histologic diagnoses for 151 women who were referred to the Johns Hopkins Hospital colposcopy clinic for evaluation of an abnormal Pap smear. HPVs were identified as “high-risk” or “low-risk” by Hybrid Capture. The final disease status was categorized as high-grade squamous intraepithelial lesion (HSIL) by histology (n= 26), low-grade squamous intraepithelial lesion (LSIL) by histology (n= 43), equivocal [histology negative, cytology atypical squamous cells of undetermined significance (ASCUS) or higher,n= 42], and negative (both histology and cytology negative,n= 40). Thirty-five percent of disease-negative women and 84% of the women with biopsy-proven or equivocal disease were HPV-positive. Ninety-two percent of the HPV-positive women harbored high-risk HPVs, either high-risk HPVs alone (77%) or high-risk HPVs along with low-risk HPVs (15%). High-risk HPVs predominated in disease-negative as well as disease-positive women. Collection of specimens with a cytobrush was more efficient for HPV DNA detection than collection by cervicovaginal lavage. Large amounts of HPV DNA correlated with presence of HSIL or LSIL. For detection of HSIL, considering only brush samples, the sensitivities of abnormal cytology (ASCUS or higher), of high-risk HPVs, and of the two combined were, respectively, 87, 93, and 100%; the corresponding specificities were 30, 30, and 20%. HPV DNA detection may be most beneficial in populations with low HPV prevalence.