Dysplasia In HIV-infected Women Research Articles

Risk of abnormal cervical cytology in HIV-infected women testing positive for both human papillomavirus and Epstein-Barr virus in genital tract specimens.

Although infection with high-risk human papillomavirus (HPV) is a prerequisite for cervical cancer development, HPV infection is not sufficient to promote cancer in the majority of infected women. We tested the hypothesis that human herpesviruses might cooperate with HPV to promote the development of cervical dysplasia, an early indicator of cervical cancer development. This study used archived specimens from a cohort of human immunodeficiency virus (HIV)-seropositive women seeking gynecological care at the Medical Center of New Orleans, Louisiana. Viral DNA was detected by PCR amplification and risk of abnormal cervical cytology was determined in relation to virus test results. Consensus human herpesvirus PCR with herpes speciation by restriction endonuclease digestion revealed Epstein-Barr virus (EBV) to be the most prevalent herpesvirus in cervicovaginal lavage specimens. Further analysis using an EBV-specific PCR assay and cervical swab specimens demonstrated an approximately fourfold increased risk of abnormal cervical cytology in women testing positive for cervical EBV and high-risk HPV compared to women testing positive for high-risk HPV alone. This relationship was independent of markers of advancing HIV disease. Cervical shedding of EBV appears to predict a greater risk of cervical dysplasia in HIV-infected women with a high-risk HPV infection.

Human papilloma virus correlates of high grade cervical dysplasia in HIV-infected women in Mombasa, Kenya: a cross-sectional analysis

BackgroundWomen living with HIV are at increased risk to be co-infected with HPV, persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR HPV viral load, which make them more at risk for cervical cancer. Despite their inherent vulnerability, there is a scarcity of data on potential high risk (pHR) and HR HPV genotypes in HIV- infected women with cervical dysplasia and HPV-type specific viral load in this population in Sub Saharan Africa.The aim of this analysis of HIV-infected women was to explore the virological correlates of high-grade cervical dysplasia (CIN 2+) in HIV-infected women, thereby profiling HPV genotypes.MethodThis analysis assesses baseline data obtained from a cohort study of 74 HIV-infected women with abnormal cytology attending a Comprehensive Care Centre for patients with HIV infection in Mombasa, Kenya. Quantitative real-time PCR was used for HPV typing and viral load.ResultsCIN 2 was observed in 16% (12/74) of women, CIN 3 in 23% (17/74), and, invasive cervical carcinoma (ICC) in 1% (1/74) of women. In women with CIN 3+, HPV 16 (44%), HPV 56 (33%), HPV 33 and 53 (HPV 53 (28%) were the most prevalent genotypes. HPV 53 was observed as a stand-alone HPV in one woman with ICC.A multivariate logistic regression adjusting for age, CD4 count and HPV co-infections suggested the presence of HPV 31 as a predictor of CIN 2+ (adjusted odds ratio [aOR]:4.9; p = 0.05; 95% (Confidence Interval) [CI]:1.03–22.5). Women with CIN2+ had a significantly higher viral log mean of HPV 16, (11.2 copies/ 10,000 cells; 95% CI: 9.0–13.4) than with CIN 1.ConclusionThe high prevalence of HPV 53 in CIN 3 and as a stand-alone genotype in the patient with invasive cervical cancer warrants that its clinical significance be further revisited among HIV-infected women. HPV 31, along with elevated means of HPV 16 viral load were predictors of CIN 2 + .

Prevalence of Anal HPV and Anal Dysplasia in HIV-Infected Women From Johannesburg, South Africa.

Anal cancer is a relatively common cancer among HIV-infected populations. There are limited data on the prevalence of anal high-risk human papillomavirus (HR-HPV) infection and anal dysplasia in HIV-infected women from resource-constrained settings. A cross-sectional study of HIV-infected women aged 25-65 years recruited from an HIV clinic in Johannesburg, South Africa. Cervical and anal swabs were taken for conventional cytology and HR-HPV testing. Women with abnormal anal cytology and 20% of women with negative cytology were seen for high-resolution anoscopy with biopsy of visible lesions. Two hundred women were enrolled. Anal HR-HPV was found in 43%. The anal cytology results were negative in 51 (26%); 97 (49%) had low-grade squamous intraepithelial lesions (SIL), 32 (16%) had atypical squamous cells of unknown significance, and 19 (9.5%) had high-grade SIL or atypical squamous cells suggestive of high-grade SIL. On high-resolution anoscopy, 71 (36%) had atypia or low-grade SIL on anal histology and 17 (8.5%) had high-grade SIL. Overall, 31 (17.5%) had high-grade SIL present on anal cytology or histology. Abnormal cervical cytology was found in 70% and cervical HR-HPV in 41%. We found a significant burden of anal HR-HPV infection, abnormal anal cytology, and high-grade SIL in our cohort. This is the first study of the prevalence of anal dysplasia in HIV-infected women from sub-Saharan Africa. Additional studies are needed to define the epidemiology of these conditions, as well as the incidence of anal cancer, in this population.

Anal dysplasia in HIV-infected women: a commentary on the field.

Anal cancer may be an emerging clinical problem in HIV-infected women particularly in resource-limited settings. Human papillomavirus (HPV) infection is a precursor to anal cancer and is prevalent in HIV-infected women, but the natural history of HPV infection and anal cancer precursors is not well described in this population. It is not known which specific dysplastic lesions in the anus are most likely to progress, and whether treatment of high grade squamous intraepithelial lesion reduces the incidence of anal cancer in women. Cervical HPV infection and associated lesions may be related to the pathogenesis and natural history of anal disease. Cervical screening is resource intensive but some limited infrastructure exists in most areas where cervical cancer is prevalent. Anal screening, however is not performed. It may be that the infrastructure for cervical screening may be leveraged in developing the appropriate research, screening and treatment tools for anal dysplasia.

Cost-effectiveness of using the Cervex-Brush (broom) compared to the elongated spatula for collection of conventional cervical cytology samples within a high-burden HIV setting: a model-based analysis.

BackgroundFrom 2010 to 2014, approximately 2 million Pap smears from HIV-infected women were submitted to the South African National Health Laboratory Services (NHLS) through the national cervical cancer screening programme. The objective of this analysis was to determine whether using the plastic Cervex brush (“broom”) would be a cost-effective approach to improve cytology specimen quality as compared to the wooden spatula used currently.MethodsA decision analysis model was built using the expected adequacy rates for samples collected with the spatula (<$0.02) and broom ($0.23) and the probability of detecting cervical dysplasia. NHLS data was used for testing volumes and rates of HIV-positivity, suitability of specimens, and presence of endocervical cells. Expected positivity of Pap smears in HIV-infected women (73 %), odds ratios of the effectiveness of the broom (OR: 1.57), and improved sensitivity when endocervical cells present (OR: 1.89) are from literature. NHLS costs were used for the collection devices and conventional cytology ($4.89). Cost of clinic visit is from WHO CHOICE ($8.36).ResultsIn 2010, 80 % of specimens submitted to NHLS were adequate for evaluation; in 2014, only 54 % met the same criteria. For HIV-infected women, according to the guidelines model, using the wooden spatula costs $6.25 million per year, $16.79 per woman tested. Under intended practice, for each additional HSIL case detected among HIV-infected women, the South African cervical cancer screening programme could save $13.64 (95 % CI: $13.52 to $13.76) by using the broom as its standard of care collection device through increased collection of endocervical cells and consequent reduction in repeat Pap smears.ConclusionUnder a wide range of parameters tested using a simulation model, the more expensive plastic broom could save the South African cervical cancer screening programme money and increase detection of high-grade cervical dysplasia in HIV-infected women compared to the current wooden spatula.

A systematic review of the effects of visual inspection with acetic acid, cryotherapy, and loop electrosurgical excision procedures for cervical dysplasia in HIV-infected women in low- and middle-income countries.

Cervical cancer, almost all of which is caused by human papillomavirus, accounts for 12% of female cancers worldwide and is more common among HIV-infected women. Nine of 10 deaths from cervical cancer occur in low- and middle-income countries (LMICs). Simple screening methods and outpatient treatment of precursor lesions save lives but the benefit of these interventions among HIV-infected women is uncertain. We reviewed evidence of the effects of screening with visual inspection with acetic acid (VIA), and outpatient treatment for cervical precancer among HIV-infected women in LMIC. A systematic review of articles published from January 1995 through July 2013 was conducted using key terms for VIA cervical screening, cervical precancer treatment with cryotherapy or loop electrosurgical excision procedure, HIV-infected women, low-resource settings, and outcomes, including morbidity and mortality. Of 2159 articles screened, 14 met inclusion criteria; all considered only morbidity outcomes. No articles dealt with the long-term impact of screening/treatment on cervical cancer incidence or mortality among HIV-infected women. Articles reported on performance of VIA, prevalence of cervical dysplasia, and complications and rates of recurrent dysplasia after treatment. Dysplasia prevalence and recurrence were higher among HIV-infected compared with HIV-uninfected women but morbidity from treatment was similar. Few data exist on long-term outcomes of VIA, cryotherapy, or loop electrosurgical excision procedure interventions among HIV-infected women in LMIC; longer-term outcomes research is needed to assess the effects of VIA or other screening modalities and outpatient treatment on prevention of cervical cancer among HIV-infected women.

Combination antiretroviral therapy reduces the detection risk of cervical human papilloma virus infection in women living with HIV.

Data on the effect of combination antiretroviral therapy (cART) on cervical human papilloma virus (HPV) infection are both limited and conflicting. We aimed to determine the effect of the initiation of cART for HPV genotype detection on cervical samples in HIV-infected South African women. Prospective cohort study. Generalized estimating equation was performed to estimate parameters of mixed-effects logistic regression models of cART on HPV cervical detection risk, adjusting for time-dependent covariates CD4 T-cell count, sexual activity and excision treatment. Ratio of odds ratios (ORs) was computed to compare the pooled cART effect on lower vs. high-risk HPV genotype groups, to the effect of cART on the risk of HPV-16 detection. Of the 300 patients, 204 (68%) were commenced on ART during follow-up, as they met the criteria for cART initiation. cART significantly reduced the risk for detection of HPV by 77% [OR 0.23, 95% confidence interval (CI) 0.15-0.37]. cART significantly reduced the risk of HPV-16 detection (OR 0.50, 95% CI 0.37-0.67). Every month on cART significantly reduced the detection risk of any HPV type by 9% (OR 0.91, 95% CI 0.89-0.94). The protective effect of cART on the detection risk for the low-risk HPV genotype group was significantly less than the protective effect of cART on the detection risk of HPV-16 (ratio of ORs 1.35, 95% CI 1.22-1.50). cART significantly reduced cervical HPV infection. This effect was dependent on the duration of exposure to cART and is the mechanism by which cART may improve the outcome of dysplasia in HIV-infected women.

Progression and regression of premalignant cervical lesions in HIV-infected women from Soweto: a prospective cohort

To ascertain progression and regression of cervical dysplasia in HIV-infected women in Soweto. Prospective cohort. Women attending an HIV wellness clinic were offered cervical smears as part of care; smears were assessed using the Bethesda system. Those with high-grade lesions or worse were referred for colposcopy. Progression analyses included women with at least two smears at least 5.5 months apart. Hazard ratios were used to ascertain predictors of progression. Two thousand, three hundred and twenty-five women had a baseline smear; their median age and CD4 cell count was 32 years and 312 cells/μl, respectively; 17% were taking highly active antiretroviral therapy (HAART); 62, 20 and 14% had normal, low-grade squamous intraepithelial lesions (LSIL) or high-grade squamous intraepithelial lesions (HSIL), respectively. Of those with baseline normal or LSIL smears, 1074 had another smear; progression from normal to LSIL was 9.6/100 person-years (95% CI 8.3-11.1) and progression from normal or LSIL to HSIL was 4.6/100 person-years (95% CI 3.9-5.5). Of 225 women with LSIL at baseline and at least one subsequent smear at least 11.5 months later, 44.0% regressed to normal (21.2/100 person-years (95% CI 17.5-25.7)). Multivariate models suggested increasing risk for progression in women with CD4 cell count below 500 cells/μl and HAART may reduce the risk of progression [adjusted hazard ratio (aHR) 0.72 (0.52-0.99)]. HIV-infected women have high rates of prevalent and incident HSIL and LSIL with relatively low risk of regression to normal from LSIL. HAART appears to protect against progression. Our findings suggest cervical screening intervals should be less than 10 years - irrespective of age in women with CD4 cell counts below 500 cells/μl.

Cervical and anal HPV infection and dysplasia in HIV-infected women

Methods We performed a pilot, prospective, observational study on 100 HIV-infected women presenting for routine HIV care. Subjects were interviewed and underwent cervical and anal testing with cytology and HPV with Hybrid Capture 2 assay (Digene Corporation, Gaithersburg, MD). High resolution anoscopy (HRA) or colposcopy were performed if indicated and subjects with high grade dysplasia were referred for treatment. Secondary analyses were performed to assess for associated risk factors for abnormal cervical or anal cytology or HPV infection such as CD4 Tcell count using SPSS for Windows, version 15.0.

Anal Dysplasia in HIV-Infected Women with Cervical and Vulvar Dysplasia

To describe the findings of high-resolution anoscopy (HRA) in human immunodeficiency virus (HIV)-infected women with a history of lower genital tract dysplasia. A retrospective chart review of all HIV-infected women undergoing HRA from 2002 to 2003 was conducted. Demographic and clinical information, including the most recent cervical and vaginal cytologic results and colposcopic evaluations, were collected from medical records. These data were compared with anal cytologic and histologic findings from HRA. Eight patients were identified, with a mean age of 42 years. The mean duration of known HIV infection was 12 years. All eight patients had a previous history of treatment for cervical dysplasia or carcinoma. Five patients also had a history of high-grade vulvar dysplasia. The most recent cervical and vaginal cytologic results for all patients were abnormal. Seven patients underwent HRA because of suspected anal intraepithelial neoplasia (AIN); of these, four patients had perianal warts and three had diffuse high-grade vulvar dysplasia. One patient was referred for HRA because of high-grade dysplasia on vaginal cytologic analysis with a negative colposcopic and urologic evaluation. All eight patients (100%) had abnormal anal cytologic results with histologically proven AIN. Five patients had AIN 2,3, and three patients had AIN 1 and anal condyloma. Two of the three patients with AIN 1 had high-grade perianal dysplasia. High-resolution anoscopy identified anal dysplasia in 100% of eight HIV-infected women with human papilloma virus-related dysplasia of the lower genital tract. High-resolution anoscopy should be considered as part of the evaluation for the extent of disease in HIV-infected women with cervical and vaginal dysplasia, condyloma, and dysplasia of the perineum.