The Prevalence of Precancerous Cervical Cancer Lesion among HIV-Infected Women in Southern Ethiopia: A Cross-Sectional Study

Introduction

The magnitude of precancerous cervical cancer lesions as well as invasive cervical cancer is higher in HIV-infected women than non HIV-infected women. Thus, screening targeting HIV-infected women is being undertaken in developing countries, including Ethiopia. However, data on the prevalence and determinants of precancerous cervical cancer lesion among HIV-infected women in southern Ethiopia is lacking. Thus, this study aimed to assess the prevalence of and factors associated with precancerous cervical cancer lesion among HIV- infected women in southern Ethiopia.

Methods

A hospital-based cross-sectional study was conducted from October 2012 to February 2013 among HIV-infected women in Southern Ethiopia. Four hundred forty eight HIV-infected women who had been screened and treated for precancerous cervical cancer lesion were included in the study. Data were collected by using structured and pretested questionnaire. Visual inspection with acetic acid was applied for screening and treatment. SPSS version 16.0 was used for data entry and analysis. Logistic regression analysis was fitted and odds ratios with 95% Confidence intervals and p-values were computed to identify factors associated with precancerous cervical cancer lesion.

Results

Out of 448 study participants, 99 (22.1%) were found to be positive for precancerous cervical cancer. Being currently on highly active antiretroviral treatment (AOR=0.52, 95%CI: 0.35, 0.92), history of sexually transmitted disease (AOR=2.30, 95%CI: 1.23, 4.29) and having only one lifetime sexual partner (AOR=0.33, 95%CI: 0.20, 0.56) were factors associated with precancerous cervical cancer lesion.

Conclusions

The prevalence of precancerous cervical cancer lesion among HIV-infected women in southern Ethiopia was found to be high. Intervention to access all HIV-infected women like scaling up the limited services and awareness creation should be undertaken. Measures aimed at preventing the acquisition and transmission of sexually transmitted diseases and reducing the number of sexual partners are required. Besides, early initiation of highly active antiretroviral treatment is important.     

Potential impact of antiretroviral therapy and screening on cervical cancer mortality in HIV-positive women in sub-Saharan Africa: a simulation

Background

Despite having high cervical cancer incidence and mortality rates, screening for cervical precancerous lesions remains infrequent in sub-Saharan Africa. The need to screen HIV-positive women because of the higher prevalence and faster progression of cervical precancerous lesions may be heightened by the increased access to highly-active antiretroviral therapy (HAART). Policymakers need quantitative data on the effect of HAART and screening to better allocate limited resources. Our aim was to quantify the potential effect of these interventions on cervical cancer mortality.

Methods and Findings

We constructed a Markov state-transition model of a cohort of HIV-positive women in Cameroon. Published data on the prevalence, progression and regression of lesions as well as mortality rates from HIV, cervical cancer and other causes were incorporated into the model. We examined the potential impact, on cumulative cervical cancer mortality, of four possible scenarios: no HAART and no screening (NHNS), HAART and no screening (HNS), HAART and screening once on HAART initiation (HSHI), and HAART and screening once at age 35 (HS35). Our model projected that, compared to NHNS, lifetime cumulative cervical cancer mortality approximately doubled with HNS. It will require 262 women being screened at HAART initiation to prevent one cervical cancer death amongst women on HAART. The magnitudes of these effects were most sensitive to the rate of progression of precancerous lesions.

Conclusions

Screening, even when done once, has the potential of reducing cervical cancer mortality among HIV-positive women in Africa. The most feasible and cost-effective screening strategy needs to be determined in each setting.     

High prevalence of hypertension and placental insufficiency, but no in utero HIV transmission, among women on HAART with stillbirths in Botswana

Background

Increased stillbirth rates occur among HIV-infected women, but no studies have evaluated the pathological basis for this increase, or whether highly active antiretroviral therapy (HAART) influences the etiology of stillbirths. It is also unknown whether HIV infection of the fetus is associated with stillbirth.

Methods

HIV-infected women and a comparator group of HIV-uninfected women who delivered stillbirths were enrolled at the largest referral hospital in Botswana between January and November 2010. Obstetrical records, including antiretroviral use in pregnancy, were extracted at enrollment. Verbal autopsies; maternal HIV, CD4 and HIV RNA testing; stillbirth HIV PCR testing; and placental pathology (blinded to HIV and treatment status) were performed.

Results

Ninety-nine stillbirths were evaluated, including 62 from HIV-infected women (34% on HAART from conception, 8% on HAART started in pregnancy, 23% on zidovudine started in pregnancy, and 35% on no antiretrovirals) and 37 from a comparator group of HIV-uninfected women. Only 2 (3.7%) of 53 tested stillbirths from HIV-infected women were HIV PCR positive, and both were born to women not receiving HAART. Placental insufficiency associated with hypertension accounted for most stillbirths. Placental findings consistent with chronic hypertension were common among HIV-infected women who received HAART and among HIV-uninfected women (65% vs. 54%, p = 0.37), but less common among HIV-infected women not receiving HAART (28%, p = 0.003 vs. women on HAART).

Conclusions

In utero HIV infection was rarely associated with stillbirths, and did not occur among women receiving HAART. Hypertension and placental insufficiency were associated with most stillbirths in this tertiary care setting.     

Acceptability and Accuracy of Cervical Cancer Screening Using a Self-Collected Tampon for HPV Messenger-RNA Testing among HIV-Infected Women in South Africa

Background

HIV increases women’s risk for high-risk human papillomavirus (hrHPV) infection and invasive cervical cancer. South Africa has a high HIV prevalence but low cervical cancer screening coverage. Self-collection of cervical specimens and hrHPV testing, including hrHPV messenger-RNA (mRNA) testing, are methods aimed at increasing screening rates. However, data are limited on the acceptability and accuracy of tampon-based self-collection for hrHPV mRNA testing in HIV-infected women.

Methods

We recruited 325 HIV-infected women seeking care at a government HIV clinic in Pretoria, South Africa. A clinician performed a pelvic examination and obtained an endocervical specimen. Study participants performed self-collection using a tampon. Both clinician- and self-collected specimens were tested for hrHPV mRNA. Acceptability of both collection methods was assessed, the prevalence of hrHPV mRNA in our study population was estimated, test positivity of the two collection methods were compared, and test agreement was assessed by calculating the κ-statistic, sensitivity, and specificity.

Results

Over 90% of women reported no difficulties self-collecting specimens and 82% were willing to perform the tampon-collection at home. Based on clinician-collection specimens, the prevalence of hrHPV mRNA in our study population was 36.7% (95% CI: 31.4%– 42.0%). There was no difference in test positivity between clinician-collection, 36.7%, and tampon-collection, 43.5% (p-value = 0.08). Using clinician-collection as the reference test, the sensitivity and specificity for hrHPV mRNA of tampon-collection were 77.4% (95% CI: 69.8–85.0%) and 77.8% (95% CI: 71.9–83.6%), respectively.

Conclusions

Tampon-based self-collection is acceptable to women and has similar hrHPV mRNA positivity rates as clinician-collection, but has reduced sensitivity and specificity compared to clinician-collection. The hrHPV mRNA prevalence in our study population is high, but similar to other high-risk populations, and highlights the need for improved cervical cancer screening. Further research into the optimal use of tampon-based collection as a cervical cancer screening tool is warranted.     

Prospective One Year Follow Up of HIV Infected Women Screened for Cervical Cancer Using Visual Inspection with Acetic Acid,Cytology and Human Papillomavirus Testing in Johannesburg South Africa

Background

Cervical cancer is the most common cancer in Sub-Saharan Africa. There are little of HIV-infected women one-year after screening using visual inspection with acetic acid (VIA), HPV or cytology in sub-Saharan Africa.

Methods

HIV-infected women in Johannesburg South Africa were screened one year later by Pap smear, VIA and human papillomavirus (HPV) testing. Women qualified for the 12 month follow-up visit if they had a negative or cervical intra-epithelial neoplasia (CIN) 1 results at the baseline visit. Modified Poisson regression was used to analyse associations between patient baseline characteristics and progression.

Results

A total of 688 of 1,202 enrolled at baseline study who were CIN-2+ negative and qualified for a 12 month follow-up visit. Progression to CIN-2+ was higher in women with positive VIA results (12.6%; 24/191) than those VIA-negative (4.4%; 19/432). HPV-positive women at baseline were more likely to progress to CIN-2+ (12.3%; 36/293) than those HPV-negative (2.1%; 7/329). Cytology-positive women at baseline were more likely to progress to CIN-2+ (9.6%; 37/384) than cytology-negative women (2.5%; 6/237). Approximately 10% (10.4%; 39/376) of women with CIN 1 at baseline progressed to CIN 2+. Women who were VIA or HPV positive at baseline were more likely to progress aIRR 1.85, CI 95% (1.46 to 2.36), aIRR 1.41 CI 95% (1.14 to 1.75) respectively.

Conclusion

Progression to CIN-2+ in HIV-infected women is significant when measured by baseline positive VIA, HPV or Pap and yearly screening by any method should be considered in this population if possible.     

The Association between HIV Infection,Antiretroviral Therapy and Cervical Squamous Intraepithelial Lesions in South Western Nigerian Women

Introduction

Findings from studies that evaluated the effect of antiretroviral drug use on the development of cervical squamous intraepithelial lesion differed in their conclusions. This study investigated the association between HIV infection, antiretroviral drug use and cervical squamous intraepithelial lesion in a high HIV and cervical cancer burden setting- Nigeria.

Methods

A cross sectional study among 1140 women of known HIV status enrolled in a randomised study to determine the test characteristics of visual inspection in detecting cytology diagnosed squamous intraepithelial lesion. Multivariate analysis was used to determine the association between HIV infection, antiretroviral drug use and the twin outcome variables of cervical squamous intraepithelial lesion (SIL) and High grade squamous intraepithelial lesion (HSIL) while controlling for confounders.

Results

Prevalence of cervical squamous intraepithelial lesion was 8.5%, with a higher prevalence of 14.3% in HIV positive compared to 3.3% in HIV negative women (aOR: 5.4; 95% CI: 2.9–8.8). Not using antiretroviral drugs was found to be associated with an increased risk of SIL (aOR: 2.1; 95% CI: 1.4–3.5) and HSIL (aOR: 2.6; 95% CI: 1.1–6.4). Participants who had a CD4 cell count <200 cells/mm³, were also found to be at increased risk for SIL (aOR: 1.9; 95% CI: 1.1–5.9) and HSIL (aOR: 5.7; 95% CI: 1.1–7.2).

Conclusion

HIV infection and severe immunosuppression were found to be associated with increased risk of cervical squamous intraepithelial lesion but not viral load. For the first time, in the West African sub-region with specific HIV type and strains, we established the protective effect of antiretroviral drug use against the development of SIL. Integration of cervical cancer screening programme into HIV services and early initiation of antiretroviral drug in HIV positive women especially those with severe immune-suppression could therefore prove to be useful in preventing and controlling cervical cancer development in HIV positive women.     

Cervical Cancer Screening Service Uptake and Associated Factors among Age Eligible Women in Mekelle Zone,Northern Ethiopia, 2015: A Community Based Study Using Health Belief Model

Introduction

Cervical cancer is the third most common cancer among women worldwide, with about 500,000 new patients diagnosed and over 250,000 deaths every year. Cervical cancer screening offers protective benefits and is associated with a reduction in the incidence of invasive cervical cancer and cervical cancer mortality. But there is very low participation rate in screening for cervical cancer among low and middle-income countries.

Objective

This study aimed to determine cervical cancer screening service uptake and its associated factor among age eligible women in Mekelle zone, northern Ethiopia, 2015.

Methods

A community based cross-sectional study was conducted in Mekelle zone among age eligible women from February to June 2015. Systematic sampling technique was used to select 1286 women in to the study. A pre-tested structured questionnaire was used to collect relevant data. Data was entered and cleaned using EPINFO and analyzed using SPSS version 20 software package. Bivariate and Multivariate logistic regression was performed to assess association between dependent and independent variables with 95% CI and p-value less than 0.05 was set for association.

Results

The study revealed that among 1186 age eligible women, only 235(19.8%) have been screened for cervical cancer. Age (AOR = 1.799, 95%CI = 1.182–2.739), history of multiple sexual partners (AOR = 1.635, 95%CI = 1.094–2.443), history of sexually transmitted disease (AOR = 1.635,95%CI = 1.094–2.443), HIV sero status (AOR = 5.614, 95%CI = 2.595–12.144), perceived susceptibility to cervical cancer (AOR = 2.225, 95%CI = 1.308–3.783), perceived barriers to premalignant cervical lesions screening (AOR = 2.256, 95%CI = 1.447–3.517) and knowledge on cervical cancer and screening (AOR = 2.355, 95%CI = 1.155–4.802) were significant predictors of cervical cancer screening service uptake.

Conclusion

Magnitude of cervical cancer screening service uptake among age eligible women is still unacceptably low. Age of the women, history of multiple sexual partners and sexually transmitted disease, HIV sero-positivity, Knowledge, Perceived susceptibility and Perceived Barrier were important predictors of cervical cancer screening service uptake.     

Prevalence and Predictors of Colposcopic-Histopathologically Confirmed Cervical Intraepithelial Neoplasia in HIV-Infected Women in India

Background

Prevalence estimates of cervical intraepithelial neoplasia (CIN) among HIV-infected women in India have been based on cervical cytology, which may have underestimated true disease burden. We sought to better establish prevalence estimates and evaluate risk factors of CIN among HIV-infected women in Pune, India using colposcopy and histopathology as diagnostic tools.

Methodology

Previously unscreened, non-pregnant HIV-infected women underwent cervical cancer screening evaluation including standardized diagnostic colposcopy by a gynecologist. Histopathologic confirmation was conducted among consenting women with clinical suspicion of CIN. The prevalence of CIN was evaluated by a composite diagnosis based on colposcopy and histopathology results. Multivariable ordinal logistic regression analysis was conducted to determine independent predictors of increasing severity of CIN.

Results

The median age of the n = 303 enrolled HIV-infected women was 30 years (interquartile range, 27–34). A majority of the participants were widowed or separated (187/303, 61.7%), more than one-third (114/302, 37.7%) were not educated beyond primary school, and nearly two-thirds (196/301, 64.7%) had a family per capita income of <1,000 Indian Rupees (∼US$22) per month. Cervical high-risk HPV-DNA was detected in 41.7% (124/297) of participants. The composite colposcopic-histopathologic diagnoses revealed no evidence of CIN in 220 out of 303 (72.6%) women, CIN1 in 33/303 (10.9%), CIN2 in 31/303 (10.2%), CIN3 in 18/303 (5.9%) and 1 (0.3%) woman was diagnosed with ICC. Thus, over a quarter of the participants [83/303: 27.7% (95% CI: 22.7–33.1)] had ≥CIN1 lesions and a sixth [50/303: 16.5% (95% CI: 12.2–21.9)] had evidence of advanced (≥CIN2) neoplastic disease. The independent predictors of increasing severity of CIN as revealed by a proportional odds model using multivariable ordinal logistic regression included (i) currently receiving antiretroviral therapy [adjusted odds ratios (aOR): 2.24 (1.17, 4.26), p = 0.01] and (ii) presence of cervical high-risk HPV-DNA [aOR: 1.93 (1.13, 3.28), p = 0.02].

Conclusions

HIV-infected women in Pune, India have a substantial burden of cervical precancerous lesions, which may progress to invasive cervical cancer unless appropriately detected and treated. Increased attention should focus on recognizing and addressing this entirely preventable cancer among HIV-infected women, especially in the context of increasing longevity due to antiretroviral therapy.     

Black and White Women in Maryland Receive Different Treatment for Cervical Cancer

Purpose

Despite an overall decrease in incidence, the death rate from cervical cancer in the United States remains higher in black women than their white counterparts. We examined the Maryland Cancer Registry (MCR) to determine treatment factors that may explain differences in outcomes between races in the state of Maryland.

Methods

Incident cervical cancers in the MCR 1992–2008 were examined. Demographics, tumor characteristics and treatments were compared between races and over time.

Results

Our analysis included 2034 (1301 white, 733 black) patients. Black women were more likely to have locally advanced or metastatic disease at diagnosis (p<0.01). They were more likely to receive any radiation or chemotherapy combined with radiation and less likely to receive surgery (p<0.01). When adjusted for stage and insurance status black women had 1.50 (95% CI 1.20–1.87) times the odds of receiving radiation and 1.43 (95% CI 1.11–1.82) times the odds of receiving chemotherapy. Black women with cervical cancer had 0.51 times the adjusted odds (95% CI 0.41–0.65) of receiving surgery compared to white women. Racial differences in treatment did not change significantly over time.

Conclusions

Surgical treatment for newly diagnosed cervical cancer in the state of Maryland was significantly less common amongst black women than white during our study period. Equivalent treatments are not being administered to white and black patients with cervical cancer in Maryland. Differences in care may contribute to racial disparities in outcomes for women with cervical cancer.     

Evaluation of Cervical Cancer Screening Programs in C?te d’Ivoire,Guyana, and Tanzania: Effect of HIV Status

Background

HIV infection increases a woman’s risk for cervical cancer, and cervical cancer incidence and mortality rates are higher in countries with high HIV prevalence and limited resources for screening. Visual inspection with acetic acid (VIA) allows screening and treatment of cervical lesions in a single-visit approach (SVA), but data on its performance in HIV-infected women are limited. This study’s objective was to examine cervical cancer screening using VIA/SVA in programs serving HIV-infected women.

Methods

A VIA/SVA program with cryotherapy for VIA-positive lesions was implemented in Côte d’Ivoire, Guyana, and Tanzania from 2009 to 2012. The effect of HIV status on VIA positivity and on presence of cryotherapy-eligible lesions was examined using a cross-sectional study design, with Chi-square tests for comparisons and constructed multivariate logistic regression models. A P-value of < 0.05 was significant.

Findings

VIA was performed on 34,921 women, 10% (3,580) were VIA positive; 2,508 (85%) eligible women received cryotherapy during the same visit; only 234 (52%) of those who postponed returned for treatment; 622 (17%) VIA-positive women had lesions too large to be treated with cryotherapy and were referred for excisional treatment. In multivariate analysis—controlling for HIV status, location of the screening clinic, facility location, facility type, and country—compared to HIV-uninfected/unknown women, HIV-infected women had higher odds of being VIA positive (OR 1.95, 95% CI 1.76, 2.16, P<0.0001) and of having large lesions requiring referral (OR 1.93, 95% CI 1.49, 2.51, P< 0.0001). Minor treatment complications occurred in 19 of 3,032 (0.63%) women; none required further intervention.

Conclusions

This study found that compared to HIV-uninfected/unknown women, HIV-infected women had nearly twice the odds of being VIA-positive and to require referral for large lesions. SVA was safe and resulted in significant reductions in loss to follow-up. There is increased need for excisional treatment in countries with high HIV prevalence.     

Distribution of Carcinogenic Human Papillomavirus Genotypes and Association to Cervical Lesions among Women in Fez (Morocco)

Objectives

To determine the distribution of cervical high-risk human papillomavirus genotypes and their association to cellular abnormalities in women from Fez and its neighborhood.

Methods

Women attending the Hassan II University Hospital for cervical pap smears were recruited after an informed consent. Interviews and two cervical samples were performed for each woman. Cervical samples were used for cytological analysis and HPV DNA detection. HPV was typed using a method based on multiplex PCR with fluorescently labeled specific primers followed by capillary electrophoresis. The study was approved by the ethics committee of the Faculty of Medicine and Pharmacy of Fez.

Results

The HPV prevalence in the studied population was 43.1% and the most prevalent types were HPV 53 (23 cases); HPV 16 (20 cases); HPV 35 (18 cases); HPV 51 (10 cases) and HPV 56 (7 cases). From the 619 confirmed pap smears, 20% were abnormal. The cytological abnormalities were significantly associated to HPV infection, women age, number of pregnancies and parity (p < 0.05).

Conclusion

More attention should be given to HPV in Morocco because it represents an important public health concern. The distribution of carcinogenic HPV types in the studied population is different from the data in other regions but epidemiological studies in other Moroccan regions are required.     

Human Papillomavirus Types Distribution in Organised Cervical Cancer Screening in France

Background

Knowledge of prevalence rates and distribution of human papillomavirus (HPV) genotypes prior high HPV vaccine coverage is necessary to assess its expected impact on HPV ecology and on cervical lesions and cancers.

Methods

Residual specimens of cervical cytology (N = 6,538) were obtained from 16 sites participating in organised cervical cancer screening pilot programs throughout France, anonymised and tested for HPV DNA using the PapilloCheck® genotyping test. Samples were stratified according to age of women and cytological grades.

Results

The age-standardised prevalence rates of HPV 16 and/or 18 (with or without other high-risk types) was 47.2% (95% Confidence Interval, CI: 42.4–52.1) in high-grade squamous intraepithelial lesions (HSILs), 20.2% in low-grade SIL (95% CI: 16.7–23.7) and 3.9% (95% CI: 2.8–5.1) in normal cytology. Overall HR HPV were detected in 13.7% (95%I CI: 11.7–15.6) of normal cytology. In women below 30 years of age, 64% of HSILs were associated with HPV16 and/or 18. In our study population, HPV16 was the most commonly detected type in all cervical grades with prevalence rates ranking from 3.0% in normal cytology to 50.9% in HSILs. HPV16 was also detected in 54% (27/50) of invasive cervical cancers including 5 adenocarcinomas.

Conclusion

HPV16 was strongly associated with cervical precancer and cancer. The high prevalence rates of HPV16/18 infection among women below 30 years of age with HSILs suggests that the impact of vaccination would be primarily observed among young women.     

Costs and Cost Effectiveness of Three Approaches for Cervical Cancer Screening among HIV-Positive Women in Johannesburg,South Africa

Background

South Africa has high rates of HIV and HPV and high incidence and mortality from cervical cancer. However, cervical cancer is largely preventable when early screening and treatment are available. We estimate the costs and cost-effectiveness of conventional cytology (Pap), visual inspection with acetic acid (VIA) and HPV DNA testing for detecting cases of CIN2+ among HIV-infected women currently taking antiretroviral treatment at a public HIV clinic in Johannesburg, South Africa.

Methods

Method effectiveness was derived from a validation study completed at the clinic. Costs were estimated from the provider perspective using micro-costing between June 2013-April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered. Threshold analysis was used to explore the potential for reducing the cost of HPV DNA testing.

Results

VIA was least costly in both scenarios. In the higher volume scenario, the average cost per procedure was US$ 3.67 for VIA, US$ 8.17 for Pap and US$ 54.34 for HPV DNA. Colposcopic biopsies cost on average US$ 67.71 per procedure. VIA was least sensitive but most cost-effective at US$ 17.05 per true CIN2+ case detected. The cost per case detected for Pap testing was US$ 130.63 using a conventional definition for positive results and US$ 187.52 using a more conservative definition. HPV DNA testing was US$ 320.09 per case detected. Colposcopic biopsy costs largely drove the total and per case costs. A 71% reduction in HPV DNA screening costs would make it competitive with the conservative Pap definition.

Conclusions

Women need access to services which meet their needs and address the burden of cervical dysplasia and cancer in this region. Although most cost-effective, VIA may require more frequent screening due to low sensitivity, an important consideration for an HIV-positive population with increased risk for disease progression.     

The Cost-Effectiveness of Directly Observed Highly-Active Antiretroviral Therapy in the Third Trimester in HIV-Infected Pregnant Women

Background

In HIV-infected pregnant women, viral suppression prevents mother-to-child HIV transmission. Directly observed highly-active antiretroviral therapy (HAART) enhances virological suppression, and could prevent transmission. Our objective was to project the effectiveness and cost-effectiveness of directly observed administration of antiretroviral drugs in pregnancy.

Methods and Findings

A mathematical model was created to simulate cohorts of one million asymptomatic HIV-infected pregnant women on HAART, with women randomly assigned self-administered or directly observed antiretroviral therapy (DOT), or no HAART, in a series of Monte Carlo simulations. Our primary outcome was the quality-adjusted life expectancy in years (QALY) of infants born to HIV-infected women, with the rates of Caesarean section and HIV-transmission after DOT use as intermediate outcomes. Both self-administered HAART and DOT were associated with decreased costs and increased life-expectancy relative to no HAART. The use of DOT was associated with a relative risk of HIV transmission of 0.39 relative to conventional HAART; was highly cost-effective in the cohort as a whole (cost-utility ratio $14,233 per QALY); and was cost-saving in women whose viral loads on self-administered HAART would have exceeded 1000 copies/ml. Results were stable in wide-ranging sensitivity analyses, with directly observed therapy cost-saving or highly cost-effective in almost all cases.

Conclusions

Based on the best available data, programs that optimize adherence to HAART through direct observation in pregnancy have the potential to diminish mother-to-child HIV transmission in a highly cost-effective manner. Targeted use of DOT in pregnant women with high viral loads, who could otherwise receive self-administered HAART would be a cost-saving intervention. These projections should be tested with randomized clinical trials.     

Population-Level Scale-Up of Cervical Cancer Prevention Services in a Low-Resource Setting: Development,Implementation, and Evaluation of the Cervical Cancer Prevention Program in Zambia

Background

Very few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries.

Methods

In a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts.

Findings

Between 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25–49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women.

Interpretation

We creatively disrupted the ''no screening'' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps.     

A Single-Arm,Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

Background

Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings.

Methods

Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital''s Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration.

Results

A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6–73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6–82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9–65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions.

Conclusions

These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy.

Trial Registration

ISRCTN Registry 48776874     

Prevalence of Hypertension in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART) Compared with HAART-Na?ve Patients at the Limbe Regional Hospital,Cameroon

Background

Highly active antiretroviral therapy (HAART) has greatly reduced the morbidity and mortality of HIV/AIDS patients but has also been associated with increased metabolic complications and cardiovascular diseases. Data on the association between HAART and hypertension (HTN) in Africa are scarce.

Objectives

Primarily to compare the prevalence of HTN in HIV/AIDS patients on HAART and HAART-naïve patients in Limbe, Cameroon; and secondarily to assess other socio-demographic and clinical factors associated with HTN in this population.

Methods

A cross-sectional study was conducted at the Limbe Regional Hospital HIV treatment center between April and June 2013, involving 200 HIV/AIDS patients (100 on first-line HAART regimens for at least 12 months matched by age and sex to 100 HAART-naïve patients). HTN was defined as a systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg.

Results

The prevalence of HTN in patients on HAART was twice (38%; 95% CI: 28.5–48.3) that of the HAART-naïve patients (19%; 95% CI, 11.8–28.1), p = 0.003. In multivariate analyses adjusted for age, gender, smoking, family history of HTN, and BMI-defined overweight, HAART was associated with HTN, the adjusted odds ratio of the HAART-treated versus HAART-naïve group was 2.20 (95% CI: 1.07–4.52), p = 0.032. HTN was associated with older age and male gender, in the HAART group and with BMI-defined overweight in the HAART-naïve group.

Conclusion

The prevalence of hypertension in HIV/AIDS patients in Limbe stands out to be elevated, higher in patients on HAART compared to those not on treatment. Blood pressure and cardiovascular risk factors should be routinely monitored. Other factors such as diet, weight control and physical exercise should also be considered.     

Human Papillomavirus Type-Specific Prevalence in the Cervical Cancer Screening Population of Czech Women

Background

Infection with high-risk human papillomavirus (HPV)types has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice.

Objectives

The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV.

Methods

Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2) and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB).

Results

Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393) of women were positive for any HPV type by BS-RLB, 18.2% (254/1393) by HR HC2, and 22.3% (310/1393) by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%). HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years.

Conclusions

Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future.     

Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping,in Comparison to Cytology

Objectives

The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening.

Methods

The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein.

Results

Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology).

Conclusion

HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women.