The purpose of this study was to determine the prevalence and risk factors for cervical squamous intraepithelial lesions (SIL) among women infected with human immunodeficiency virus type 1 (HIV-1) receiving care at the Federal Medical Center Makurdi, Nigeria.
Between March and December 2009, a total of 253 women infected with HIV-1 had cervical smears taken for cytology. HIV-1 RNA viral load and CD4 counts were also measured.
Of the 253 women, cervical SIL were present in 45 (17.8%). However, abnormal cervical cytology was noted in 146 (57.7%). Of those with abnormal cervical cytology, 101 (39.9%) women had atypical squamous cells of undetermined significance, 16 (6.3%) had low-grade SIL, and 29 (11.5%) women had high-grade SIL. The median CD4 lymphocyte count was lower in participants with cervical SIL compared with those without (132 versus 184 cells/mm3; P = 0.03). The median HIV-1 RNA viral load was higher in women with cervical SIL (102,705 versus 64,391 copies/mL; P = 0.02). A CD4 lymphocyte count of <200 cells/mm3 and an HIV-1 RNA viral load of <10,000 copies/mL were found to be significantly associated with cervical SIL.
A high prevalence of cervical SIL was found among HIV-1-infected women in Makurdi, Nigeria. Increased immune suppression and HIV-1 viremia are significantly associated with cervical SIL.
cervical squamous intraepithelial lesions; human immunodeficiency virus; risk factors; immunosuppression; cervical dysplasia; Nigeria
Ukraine has the highest antenatal HIV prevalence in Europe. The national prevention of mother-to-child transmission (MTCT) programme has reduced the MTCT rate, but less attention has been given to the prevention of unintended pregnancy among HIV-positive women. Our objectives were to describe the reproductive health, condom use and family planning (FP) practices of HIV-positive childbearing Ukrainian women and to identify factors associated with different methods of post-natal contraception.
HIV-infected childbearing women, diagnosed before or during pregnancy, were enrolled prospectively in a post-natal cohort study in four regional HIV/AIDS centres in Ukraine from December 2007. Logistic regression models were used to identify factors associated with post-natal FP practices.
Data were available for 371 women enrolled by March 2009; 82% (n = 303) were married or cohabiting, 27% (97 of 363) reported a current HIV-negative sexual partner and 69% were diagnosed with HIV during their most recent pregnancy. Overall, 21% (75 of 349) of women were not using contraception post-natally (of whom 80% reported no current sexual activity), 50% (174 of 349) used condoms, 20% (74 of 349) relied solely/partially on coitus interruptus and 4% used hormonal methods or intrauterine device. Among married/cohabiting women, consistent use of condoms in the previous pregnancy [AOR 1.96 (95%CI 1.06–3.62)], having an HIV-positive partner [AOR 0.42 (0.20–0.87)], current sexual activity [AOR 4.53 (1.19–17.3)] and study site were significantly associated with post-natal condom use; 16% of those with HIV-negative partners did not use condoms. Risk factors for non-use of FP were lack of affordability [AOR 6.34 (1.73–23.2)] and inconsistent use of condoms in the previous pregnancy [AOR 7.25 (1.41–37.2)].
More than 40% of HIV-positive women in this population are at risk of unintended pregnancy and the one in six women in HIV-discordant couples not using barrier methods risk transmitting HIV to their partners. Our study results are limited by the observational nature of the data and the potential for both measured and unmeasured confounding.
HIV; family planning; condom; prevention; mother-to-child transmission of HIV
High-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.
We 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.
Median 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.
The 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.
To assess the prevalence of and risk factors for abnormal anal cytology and HPV infections in HIV-positive women.
We conducted an observational single center study of 100 HIV-infected women with cervical and anal specimens obtained for cytology and high risk HPV testing with Hybrid Capture 2.
Seventeen women had abnormal anal cytology, 16 had anal HPV, 21 had abnormal cervical cytology and 24 had cervical HPV. Abnormal anal cytology was associated with cervical HPV infection, abnormal cervical cytology and anal HPV infection in univariate analysis. In multivariate analysis, abnormal anal cytology was associated with CD4 count under 200 cells/mm3, history of STD infection and concurrent cervical cytology abnormality.
HIV-infected women are at high risk for abnormal cytology and HPV infections of both the anus and cervix. Risk factors for abnormal anal cytology include abnormal cervical cytology, cervical and anal HPV infections and low CD4 count.
anal cytology; cervical cytology; anal HPV; cervical HPV; HIV
Cervical cancer is one of the most common AIDS-related malignancies in Thailand. To prevent cervical cancer, The US Public Health Service and The Infectious Disease Society of America have recommended that all HIV-infected women should obtain 2 Pap smears 6 months apart after the initial HIV diagnosis and, if results of both are normal, should undergo annual cytological screening. However, there has been no evidence in supporting whether this guideline is appropriate in all settings - especially in areas where HIV-infected women are living in resource-constrained condition.
To determine the appropriate interval of Pap smear screenings for HIV-infected Thai women and risk factors for subsequent abnormal cervical cytology, we assessed the prevalence, cumulative incidence and associated factors of cervical cell abnormalities (atypical squamous cell of undetermined significance or higher grades, ASCUS+) among this group of patients.
The prevalence of ASCUS+ was 15.4% at the first visit, and the cumulative incidence of ASCUS+ gradually increased to 37% in the first 3.5 years of follow-up appointments (first 7 times), and tended to plateau in the last 2 years. For multivariate correlation analysis, women with a CD4 count <350 cells/μL had a significant correlation with ASCUS+ (P = 0.043). There were no associations of subsequent ASCUS+ with age, pregnancy, contraceptive method, highly active anti-retroviral treatment, assumed duration of infection, or the CD4 count nadir level.
There are high prevalence and cumulative incidence of ASCUS+ in HIV-infected Thai women. With a high lost-to-follow-up rate, an appropriate interval of Pap smear screening cannot be concluded from the present study. Nevertheless, the HIV-infected Thai women may require more than two normal semi-annual Pap smears before shifting to routinely annual cytologic screening.
U.S. cervical cancer screening guidelines for HIV-uninfected women 30 years of age and older have recently been revised, increasing the suggested interval between Pap tests from three years to five years among those with normal cervical cytology (the Pap test) who test negative for oncogenic human papillomavirus (HPV). Whether a three-year or five-year screening interval might be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown.
To determine the risk of cervical pre-cancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as two separate endpoints, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test and were negative for oncogenic HPV.
Design, Setting and Participants
Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional cohort, between October 1, 2001 and September 30, 2002, with follow-up through April 30, 2011. Clinical sites were in the Bronx, Brooklyn, Chicago, Los Angeles, San Francisco, and Washington, DC. Semi-annual visits included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using PCR. The primary analysis was truncated at five years of follow-up.
Main Outcome Measure
The five-year cumulative incidence of cervical pre-cancer and cancer.
No oncogenic HPV was detected in 369 (88%; 95% CI, 84%-91%) of the HIV-infected women and 255 (91%; 95% CI, 88%-94%) of the HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women two cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500/μL or greater. Histologic data were obtained from four of the six sites. There were six cases of CIN-2+ in N=145 HIV-uninfected women (cumulative incidence = 5% [95% CI, 1%-8%]) and nine cases in N=219 HIV-infected women (cumulative incidence = 5% [95% CI, 2%-8%]). This included one case of CIN-2+ in N=44 oncogenic HPV-negative HIV-infected women with CD4 cell counts less than 350/μL (cumulative incidence = 2% [95% CI, 0%-7%]), one case in N=47 women with CD4 cell counts of 350 to 499/μL (cumulative incidence = 2% [95% CI, 0%-7%]), and seven cases in N=128 women with CD4 cell counts of 500/μL or greater (cumulative incidence = 6% [95% CI, 2%-10%]). One HIV-infected and one HIV-uninfected woman had CIN-3, but none had cancer.
The five-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.
Background. There are limited data on high-risk human papillomavirus (hr-HPV) genotypes among HIV-positive women in Africa, and little is known about their relationship with cervical cytology in these populations. Methods. We conducted a cross-sectional study among 194 HIV-positive women (143 from Tanzania, and 51 from South Africa) to evaluate HPV genotypes among HIV-positive women with normal and abnormal cytology. Cervical samples were genotyped for HPV types, and slides were evaluated for atypical squamous cell changes according to the Bethesda classification system. Results. Prevalence of high grade squamous intraepithelial dysplasia (HSIL) was 9%. Overall, more than half (56%) of women were infected with an hr-HPV type; 94% of women with HSIL (n = 16), 90% of women with LSIL (n = 35), and 42% of women within normal limits (WNL) (n = 58) tested positive for hr-HPV. Overall, the most prevalent hr-HPV subtypes were HPV16 (26%) and HPV52 (30%). Regional differences in the prevalence of HPV18 and HPV35 were found. Conclusion. Regional differences in HPV genotypes among African women warrant the need to consider different monitoring programmes for cervical preneoplasia. HPV-based screening tests for cervical preneoplasia would be highly inefficient unless coupled with cytology screening of the HPV-positive sample, especially in HIV-positive women.
HIV-infected women living in resource-constrained nations like Zambia are now accessing antiretroviral therapy and thus may live long enough for HPV-induced cervical cancer to manifest and progress. We evaluated the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Zambia.
We screened 150 consecutive, non-pregnant HIV-infected women accessing HIV/AIDS care services in Lusaka, Zambia. We collected cervical specimens for cytological analysis by liquid-based monolayer cytology (ThinPrep Pap Test®) and HPV typing using the Roche Linear Array® PCR assay.
The median age of study participants was 36 years (range 23-49 years) and their median CD4+ count was 165/μL (range 7-942). The prevalence of SIL on cytology was 76% (114/150), of which 23.3% (35/150) women had low-grade SIL, 32.6% (49/150) had high-grade SIL, and 20% (30/150) had lesions suspicious for squamous cell carcinoma (SCC). High-risk HPV types were present in 85.3% (128/150) women. On univariate analyses, age of the participant, CD4+ cell count, and presence of any high-risk HPV type were significantly associated with the presence of severely abnormal cytological lesions (i.e., high-grade SIL and lesions suspicious for SCC). Multivariable logistic regression modeling suggested the presence of any high-risk HPV type as an independent predictor of severely abnormal cytology (adjusted OR: 12.4, 95% CI 2.62-58.1, p=0.02).
The high prevalence of abnormal squamous cytology in our study is one of the highest reported in any population worldwide. Screening of HIV-infected women in resource-constrained settings like Zambia should be implemented to prevent development of HPV-induced SCC.
HIV; Cervical Cancer; Screening; Cytology; Zambia
Ukraine has the highest HIV prevalence (1.6%) and is facing the fastest growing epidemic in Europe. Our objective was to describe the clinical, immunological and virological characteristics, treatment and response in vertically HIV-infected children living in Ukraine and followed from birth.
The European Collaborative Study (ECS) is an ongoing cohort study, in which HIV-1 infected pregnant women are enrolled and followed in pregnancy, and their children prospectively followed from birth. ECS enrolment in Ukraine started in 2000 initially with three sites, increasing to seven sites by 2009.
A total of 245 infected children were included in the cohort by April 2009, with a median age of 23 months at most recent follow-up; 33% (n = 77) had injecting drug using mothers and 85% (n = 209) were infected despite some use of antiretroviral prophylaxis for prevention of mother-to-child transmission. Fifty-five (22%) children had developed AIDS, at a median age of 10 months (IQR = 6-19). The most prevalent AIDS indicator disease was Pneumocystis jiroveci pneumonia (PCP). Twenty-seven (11%) children had died (median age, 6.2 months). Overall, 108 (44%) children had started highly active antiretroviral treatment (HAART), at a median 18 months of age; median HAART duration was 6.6 months to date. No child discontinued HAART and 92% (100/108) remained on their first-line HAART regimen to date. Among children with moderate/severe immunosuppression, 36% had not yet started HAART. Among children on HAART, 71% (69/97) had no evidence of immunosuppression at their most recent visit; the median reduction in HIV RNA was 4.69 log10 copies/mL over a median of 10 months treatment. From survival analysis, an estimated 94%, 84% and 81% of children will be alive and AIDS-free at 6, 12 and 18 months of age, respectively. However, survival increased significantly over time: estimated survival rates to 12 months of age were 87% for children born in 2000/03 versus 96% for those born in 2004/08.
One in five children had AIDS and one in ten had died. The half of children who received HAART has responded well and survival has significantly improved over time. Earlier diagnosis and prompt initiation of HAART remain key challenges.
Ukraine was the epicentre of the HIV epidemic in Eastern Europe, which has the most rapidly accelerating HIV epidemic world-wide today; national HIV prevalence is currently estimated at 1.6%. Our objective was to evaluate the uptake and effectiveness of interventions for prevention of mother-to-child transmission (PMTCT) over an eight year period within operational settings in Ukraine, within the context of an ongoing birth cohort study.
The European Collaborative Study (ECS) is an ongoing birth cohort study in which HIV-infected pregnant women identified before or during pregnancy or at delivery were enrolled and their infants prospectively followed. Three centres in Ukraine started enrolling in 2000, with a further three joining in September 2006.
Of the 3356 women enrolled, 21% (689) reported current or past injecting drug use (IDU). Most women were diagnosed antenatally and of those, the proportion diagnosed in the first/second trimester increased from 47% in 2000/01 (83/178) to 73% (776/1060) in 2006/07 (p < 0.001); intrapartum diagnosis was associated with IDU (Adjusted odds ratio 4.38; 95%CI 3.19–6.02). The percentage of women not receiving any antiretroviral prophylaxis declined from 18% (36/205) in 2001 to 7% in 2007 (61/843) (p < 0.001). Use of sdNVP alone substantially declined after 2003, with a concomitant increase in zidovudine prophylaxis. Median antenatal zidovudine prophylaxis duration increased from 24 to 72 days between 2000 and 2007. Elective caesarean section (CS) rates were relatively stable over time and 34% overall. Mother-to-child transmission (MTCT) rates decreased from 15.2% in 2001 (95%CI 10.2–21.4) to 7.0% in 2006 (95%CI 2.6–14.6). In adjusted analysis, MTCT risk was reduced by 43% with elective CS versus vaginal delivery and by 75% with zidovudine versus no prophylaxis.
There have been substantial improvements in use of PMTCT interventions in Ukraine, including earlier diagnosis of HIV-infected pregnant women and increasing coverage with antiretroviral prophylaxis and the initial MTCT rate has more than halved. Future research should focus on hard-to-reach populations such as IDU and on missed opportunities for further reducing the MTCT rate.
OBJECTIVE: To compare the prevalence and type of human papillomavirus (HPV) infections in the genital tract of human-immunodeficiency-virus- (HIV) seropositive and -seronegative women matched for cytology and to examine prospectively the relationship of HPV DNA, colposcopic findings and cervical squamous intraepithelial lesions (SIL) in these matched seropositive and seronegative cohorts. METHODS: A matched prospective study of HIV-seropositive and -seronegative women undergoing cytologic screening, colposcopy, and testing for HPV DNA and other infections at each visit. RESULTS: Twenty-three HIV-seropositive women were matched with 23 seronegative women by cervical cytology reading, lifetime number of sexual partners, age, and follow-up length. Fourteen pairs of these women had follow-up visits every 4 months, for 56 and 53 total visits in seropositive and seronegative women, respectively. After matching, the groups had a similar overall prevalence of HPV DNA and of HPV oncogenic (high risk) types at baseline. On follow up, HIV-seropositive women were more likely than seronegative women to develop SIL (38% vs. 10%), less likely to have negative cytology (34% vs. 60%, overall P = 0.03), more visits with HPV DNA detected (68% vs. 40% P = 0.04), and more visits with multiple HPV DNA types detected (18% vs. 0%, P = 0.02). Colposcopic lesions in the seropositive women were more likely to have sharp borders or mosaicism or to be thick white (P = 0.009). CONCLUSIONS: After matching for baseline Papanicolaou smear readings, these data suggest that over time seropositive women have more visits that yield abnormal cytology, more persistent HPV DNA detection, and more colposcopic abnormalities than seronegative women.
Cervical cytology and human papillomavirus (HPV) DNA co-testing is recommended as a screening method for detecting cervical lesions. However, for women who are HPV-positive but cytology-negative, the appropriate management and significance of HPV-58 infection remain unknown.
This study of prevalent HPV detected at baseline with a median follow-up of 3.2 years evaluated the risk factors associated with cervical abnormalities and assessed the significance of HPV-58 infection. A total of 265 women were enrolled. All high-grade squamous intraepithelial lesions (HSIL) that were detected by cytology were confirmed by histology. Histological diagnoses of cervical intraepithelial neoplasia 2/3 were classified as HSIL. Women were classified into four groups according to the HPV genotype that was detected at their first visit: HPV-58 (n = 27), HPV-16 (n = 52; 3 women had HPV-58 co-infection), ten other high risk (HR) types (n = 79), or low/undetermined risk types (n = 107).
Of 265 women, 20 (7.5%) had HSIL on their follow-up examinations. There were significant differences in the cumulative incidence of HSIL between the four groups (p<0.001). The 5-year cumulative incidence rates of HSIL were 34.0% (95% CI: 17.3–59.8%) in HPV-58 positive cases, 28.0% (95% CI: 13.8–51.6) in HPV-16 positive cases, 5.5% (95% CI: 2.1–14.0%) in one of the ten other types of HR-HPV positive cases, and 0% in women with low/undetermined risk HPV. When seen in women with HR-HPV (n = 158), persistent HPV infection was a significant factor associated with the development of HSIL (hazard ratio = 15.459, 95% CI: 2.042–117.045). Women with HPV-58 had a higher risk (hazard ratio = 5.260, 95% CI: 1.538–17.987) for the development of HSIL than women with HPV-16 (hazard ratio = 3.822, 95% CI: 1.176–12.424) in comparison with women with other types of HR-HPV.
HPV-58 has a high association with the development of HSIL in women who are HPV-positive and cytology-negative.
HIV-infected women are at a higher risk of cervical intraepithelial neoplasia (CIN) and cancer than women in the general population, partly due to a high prevalence of persistent human papillomavirus (HPV) infection. The aim of the study was to assess the burden of HPV infection, cervical abnormalities, and cervical cancer among a cohort of HIV-infected women as part of a routine screening in an urban overpopulated slum setting in Mumbai, India.
From May 2010 to October 2010, Médecins Sans Frontières and Tata Memorial Hospital Mumbai offered routine annual Pap smears and HPV DNA testing of women attending an antiretroviral therapy (ART) clinic and a 12-month follow-up. Women with abnormal test results were offered cervical biopsy and treatment, including treatment for sexually transmitted infections (STIs).
Ninety-five women were screened. Median age was 38 years (IQR: 33–41); median nadir CD4-count 143 cells/μL (IQR: 79–270); and median time on ART 23 months (IQR:10–41). HPV DNA was detected in 30/94 women (32%), and 18/94 (19%) showed either low-grade or high-grade squamous intraepithelial lesions (LSIL/HSIL) on Pap smear. Overall, >50% had cervical inflammatory reactions including STIs. Of the 43 women with a cervical biopsy, eight (8.4%) had CIN-1, five (5.3%) CIN-2, and two (2.1%) carcinoma in situ. All but one had HPV DNA detected (risk ratio: 11, 95% confidence interval: 3.3–34). By October 2011, 56 women had completed the 12-month follow-up and had been rescreened. No new cases of HPV infection/LSIL/HSIL were detected.
The high prevalence of HPV infection, STIs, and cervical lesions among women attending an ART clinic demonstrates a need for routine screening. Simple, one-stop screening strategies are needed. The optimal screening interval, especially when resources are limited, needs to be determined.
HIV/AIDS; HPV; women’s health; cervical cancer; operational research; India
Cancer of the cervix is the most common cancer in women in Swaziland where most women never undergo cervical screening. The extremely high prevalence of HIV/AIDS in Swaziland complicates the management of preinvasive and invasive cervical cancer. The purpose of this study was to assess the current status of cervical cytology in Swaziland, its strengths and limitations.
The study is a retrospective review of 12,188 conventional cervical smears received by the Central Public Health Laboratory in Swaziland from June 2004 to May 2006.
Review of results showed very high rates of cytologic abnormalities with 43.2% of smears screened reported as abnormal. The percentages of abnormalities were as follows: atypical squamous cells of undermined significance (ASC-US), 19.8%; atypical squamous cells, cannot exclude HSILs (ASC-H), 8.8%; low-grade squamous intraepithelial lesions (LSIL), 9.0%; high-grade squamous intraepithelial lesions (HSIL), 4.6%; squamous cell carcinomas, 0.5%; atypical endocervical cells, 0.6%; and atypical endometrial cells, 0.4%. Just over 5% of smears were inadequate. The highest rates of HSILs and invasive squamous carcinoma occurred in women aged 50–59 years.
This study underscores the need to reduce the incidence of cervical cancer and its precursor lesions in Swaziland women. Based on studies of human papillomavirus (HPV) types in other Southern African countries, current HPV vaccines would reduce the incidence and mortality from cervical cancer in the future, but cervical screening would still be required, both for women already infected with the HPV and for HPV subtypes not covered by current vaccines. The most cost-effective combination of screening modalities such as visual inspection, HPV DNA testing, and cytology should be investigated. Cervical cancer reduction needs to be managed within the greater framework of the HIV/AIDS epidemic.
Cervical screening; low resource communities; HPV
To determine the effect of cryotherapy on HIV-1 cervical shedding.
Prospective cohort study.
Five hundred HIV-positive women enrolled at an HIV treatment clinic in Nairobi, Kenya were screened for cervical cancer. Women diagnosed with cervical intraepithelial neoplasia stage 2 or 3 (CIN 2/3) by histology were offered cryotherapy treatment. The first 50 women had cervical swabs taken at baseline and at 2 and 4 weeks following treatment. Swabs were analyzed for HIV-1 RNA and compared using General Estimating Equation (GEE) with binomial or Gaussian links.
Of the 50 women enrolled, 40 were receiving antiretroviral therapy (ART) and 10 were not receiving ART at the time of cryotherapy and during study follow-up. Among all women, the odds of detectable cervical HIV-1 RNA did not increase at 2 weeks [odds ratio (OR) 1.18; 95% confidence interval (CI) 0.65–2.13] or 4 weeks (OR 1.29; 95% CI 0.71–2.33) following cryotherapy. Among 10 women not receiving ART, the OR of detectable shedding at 2 weeks was higher, but not statistically significant (OR 4.02; 95% CI 0.53–30.79; P = 0.2), and at 4 weeks remained unchanged (OR 1.00; 95% CI 0.27–3.74).
There was no increase in detectable cervical HIV-1 RNA among HIV-positive women after cryotherapy. The risk of HIV-1 transmission after cryotherapy may not be significant, particularly among women already on ART at the time of cervical treatment. However, further investigation is needed among women not receiving ART.
Africa; antiretroviral therapy; cervical intraepithelial neoplasia; cryotherapy; HIV-1; shedding
Women infected with human immunodeficiency virus (HIV) may be at higher risk of developing cervical cancer than non infected women. In a pilot study, we assessed the relationships among cervical cytology abnormalities associated to Human Papillomavirus (HPV), HIV infection and Highly Active Antiretroviral Therapy (HAART) on the development of Squamous Intraepithelial lesions (SILs). Out of the 70 HIV infected women from Douala -Cameroon (Central Africa) that we included in the study, half (35) were under HAART. After obtaining information related to their lifestyle and sexual behaviour, cervicovaginal samples for Pap smears and venous blood for CD4 count were collected and further divided into two groups based upon the presence or absence of cervical cytology abnormalities i.e. those with normal cervical cytology and those with low and high Squamous Intraepithelial lesions (LSIL, HSIL).
Assessment was done according to current antiretroviral regimens available nationwide and CD4 count. It was revealed that 44.3% of HIV-infected women had normal cytology. The overall prevalence of LSIL and HSIL associated to HPV in the studied groups was 24.3% (17/70) and 31.4% (22/70) respectively. Among the 22 HSIL-positive women, 63.6% (14/22) were not on antiretroviral therapy, while 36.4% (8/22) were under HAART. HIV infected women under HAART with positive HSIL, showed a median CD4+ T cell count of 253.7 +/- 31.7 higher than those without therapy (164.7 +/- 26.1). The incidence of HSIL related to HPV infection within the study group independently of HAART initiation was high.
These results suggest the need for extension and expansion of the current study in order to evaluate the incidence of HPV infection and cervical cancer among HIV-infected and non HIV- infected women in Cameroon.
The association between abnormal cervical cytology and HIV infection status in women was evaluated to correlate with CD4 cell count and viral load in HIV-positive patients with the presence of low-grade (LSIL) and high-grade squamous intraepithelial lesion (HSIL). Cervical samples were collected at the Tropical Disease Hospital, Maternal and Child Healthcare Hospital and at the Nascer Cidadão Maternity Hospital in Goiânia, Goiás, Brazil. An Ayre's spatula was used to collect samples from the ectocervix and a cytology brush to collect samples from the endocervix. Of a total of 237 women, 125 were HIV positive and 112 were HIV negative. Abnormal cytology (n = 21; 8.9%) was more common in the HIV positive group (n = 15; 12.1%) compared to the HIV-negative group (n = 6; 5.4%) (P = 0.05). Cytological abnormalities were not found to be associated with immunosuppression, defined as CD4 count < 200 cells/mm3. A higher frequency was found between higher viral loads (>10,000/mm3) and the presence of abnormal cytology. Pregnant women, irrespective of whether they were HIV positive or negative, were less likely to have lesions compared to the nonpregnant women in the same groups. The higher frequency of abnormal findings in Papanicolaou cytology in HIV-positive women with higher viral loads suggests the association between preinvasive cervical lesions and human immunodeficiency.
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.
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.
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].
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.
Cervical cancer is the third most common cancer among women worldwide, and in Nigeria it is the second most common female cancer. Cervical cancer is an AIDS-defining cancer; however, HIV only marginally increases the risk of cervical pre-cancer and cancer. In this study, we examine the risk factors for cervical pre-cancer and cancer among HIV-positive women screened for cervical cancer at two medical institutions in Abuja, Nigeria.
A total of 2,501 HIV-positive women participating in the cervical cancer screen-and-treat program in Abuja, Nigeria consented to this study and provided socio-demographic and clinical information. Log-binomial models were used to calculate relative risk (RR) and 95% confidence intervals (95%CI) for the risk factors of cervical pre-cancer and cancer.
There was a 6% prevalence of cervical pre-cancer and cancer in the study population of HIV-positive women. The risk of screening positivity or invasive cancer diagnosis reduced with increasing age, with women aged 40 years and older having the lowest risk (RR=0.4; 95%CI=0.2–0.7). Women with a CD4 count of 650 per mm3 or more also had lower risk of screening positivity or invasive cancer diagnosis (RR=0.3, 95%CI=0.2–0.6). Other factors such as having had 5 or more abortions (RR=1.8, 95%CI=1.0–3.6) and the presence of other vaginal wall abnormalities (RR=1.9, 95%CI=1.3–2.8) were associated with screening positivity or invasive cancer diagnosis.
The prevalence of screening positive lesions or cervical cancer was lower than most previous reports from Africa. HIV-positive Nigerian women were at a marginally increased risk of cervical pre-cancer and cancer. These findings highlight the need for more epidemiological studies of cervical cancer and pre-cancerous lesions among HIV-positive women in Africa and an improved understanding of incidence and risk factors.
Cervical cancer; Screen and treat; HIV; VIA/VILI
Cancer of the cervix rank the second most common cause of cancer related deaths among women in Sub-Saharan Africa. It is estimated that 529, 409 new cases are diagnosed annually with a mortality rate approaching 274,883 per year. Cervical Intraepithelial Neoplasia (CIN) precedes almost all cervical cancers. The incidence rate of CIN among HIV infected women is five times higher as compared to the rate in HIV negative women. The screening for cervical dysplasia and an appropriate management in women with CIN are effective methods for preventing cervical cancer. This study was done to determine the prevalence and predictors of CIN among a HIV infected women attending Care and Treatment centre (CTC) at Bugando Medical Centre (BMC).
A cross sectional survey was undertaken among HIV infected women aged 18 years and above attending at BMC CTC clinic between February and March 2013. Visual Inspection with Acetic acid (VIA) was used as the screening method for detection of CIN. Socio-demographic, reproductive and clinical information was obtained from participants and the blood was collected for CD4 lymphocyte count. Cervical punch biopsy for histological examination was performed for those who had VIA positive test. Data were entered and analyzed using STATA Version 12.0 soft ware.
A total number of 95 (26.8%) participants had positive VIA test among three hundred and fifty-five (355) HIV infected women. Histology results showed; 4(4.2%) were normal, 26 (27.4%) had an inflammatory lesion, 58(61.1%) had CIN and 7(7.3%) had invasive cervical cancer. CIN was found to be associated with a history of multiple sexual partners (P<0.001), a history of genital warts (P<0.001), and a history of STI (P = 0.010).
The Cervical Intraepithelial Neoplasia is a problem among HIV infected women. A history of multiple sexual partners, a history of genital warts, a history STI and a low baseline CD4 T lymphocyte were significant predictors for CIN. Screening for Cervical Intraepithelial Neoplasia is recommended for all women with HIV.
Cervical intraepithelial Neoplasia; HIV; Mwanza
Cervical cancer is the most common cancer in women in low-income countries. Although cervical cancer incidence and mortality is higher in HIV-positive women, resource limitations restrict the implementation of systematic screening programs in these women. We explored the potential for targeted screening by assessing the prevalence, severity and predictors of cervical squamous intra-epithelial lesions (SILs) in HIV-positive women in Cameroon.
Methods and findings
We conducted a cross-sectional study of women on antiretroviral therapy in Cameroon. Socio-demographic, behavioral, and clinical information was obtained from eligible women. Cervical exfoliated cells were then collected, a conventional cytology performed and epithelial lesions classified according to the Bethesda 2001 system.
A total of 282 women, aged 19 to 68 years, were enrolled in this study. The median CD4 count was 179 cells/microliter (interquartile range: 100 to 271). SILs were detected in 43.5% of the 276 women with satisfactory samples: including atypical squamous cells of unknown significance (ASCUS) 0.7%, low-grade SIL (LSIL) 25.0%, atypical squamous cells, cannot exclude high grade lesions (ASC-H) 14.5%, and high-grade SIL (HSIL) 3.3%. None of the demographic or clinical characteristics considered significantly predicted the presence of any SILs or the presence of severe lesions requiring colposcopy.
The prevalence of SIL in women on antiretroviral therapy in Cameroon was high underscoring the need for screening and care in this population. In the absence of any accurate demographic or clinical predictor of SIL, targeted screening does not seem feasible. Alternative affordable screening options need to be explored.
Cervical neoplasm; HIV; Screening; Cameroon; Epidemiology
OBJECTIVE: To study the prevalence of cervical squamous intraepithelial lesions (SILs) and their association with HIV-1 infection and immunodeficiency among pregnant women in Kigali, Rwanda. METHODS: As part of a cohort study on the impact of HIV-1 infection on pregnancy outcome, HIV-1 seropositive (HIV+) and seronegative (HIV-) pregnant women were enrolled during the last trimester of pregnancy at the maternity ward of the Centre Hospitalier de Kigali from July 1992 to August 1993. At inclusion, women were screened for sexually transmitted diseases (STDs)--syphilis, Neisseria gonorrhoeae, chlamydia trachomatis, Trichomonas vaginalis. CD4+ lymphocyte counts were measured and a Papanicolaou smear performed. RESULTS: Papanicolaou smear was interpretable in 103 HIV+ women and 107 HIV- women. Prevalence of SILs was significantly higher in HIV+ women than in HIV- women: 24.3% v 6.5% (odds ratio = 4.6; 95% CI: 1.8-12.3). SIL+ women (n = 32) tended to have more STDs than SIL- women (n = 178), but this did not reach a statistical difference: 37.5% and 24.7% respectively (p = 0.13). They also had a mean CD4 count significantly lower than SIL- women (623 and 784 CD4+ cells x 10(6)/l, respectively; p = 0.02). CONCLUSION: SILs were HIV related and the association with immunosuppression was statistically significant. Prevalence of SILs was high in this population of pregnant women with high HIV/STDs prevalence. Screening policy for STDs and SILs in African women should be assessed in prenatal care.
Cervical cancer and infection with human immunodeficiency virus (HIV) are both major public health problems in South Africa. The aim of this study was to determine the risk of cervical pre-cancer and cancer among HIV positive women in South Africa.
Data were derived from a case-control study that examined the association between hormonal contraceptives and invasive cervical cancer. The study was conducted in the Western Cape (South Africa), from January 1998 to December 2001. There were 486 women with invasive cervical cancer, 103 control women with atypical squamous cells of undetermined significance (ASCUS), 53 with low-grade squamous intraepithelial lesions (LSIL), 50 with high-grade squamous intraepithelial lesions (HSIL) and 1159 with normal cytology. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multiple logistic regression.
The adjusted odds ratios associated with HIV infection were: 4.4 [95% CI (2.3 – 8.4) for ASCUS, 7.4 (3.5 – 15.7) for LSIL, 5.8 (2.4 – 13.6) for HSIL and 1.17 (0.75 – 1.85) for invasive cervical cancer. HIV positive women were nearly 5 times more likely to have high-risk human papillomavirus infection (HR-HPV) present compared to HIV negative women [OR 4.6 (95 % CI 2.8 – 7.5)]. Women infected with both HIV and high-risk HPV had a more than 40 fold higher risk of SIL than women infected with neither of these viruses.
HIV positive women were at an increased risk of cervical pre-cancer, but did not demonstrate an excess risk of invasive cervical cancer. An interaction between HIV and HR-HPV infection was demonstrated. Our findings underscore the importance of developing locally relevant screening and management guidelines for HIV positive women in South Africa.
Large studies describing the profile of high-risk Human papillomavirus (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN).
We report data on 8,050 HIV-negative women, aged 17–65 years, recruited into three sequential studies undertaken in Cape Town, South Africa. Women had no history of previous cervical cancer screening. Cervical samples were tested for hrHPV DNA using the Hybrid Capture 2 (HC2) assay and all positive samples were genotyped using a PCR-based assay (Line Blot). Women underwent colposcopy and biopsy/endocervical curettage to determine CIN status. The prevalence and distribution of specific hrHPV genotypes were examined by age and CIN status.
Overall, 20.7% (95% CI, 19.9–21.6%) of women were hrHPV-positive by HC2, with women with CIN having the highest rates of positivity. Prevalence decreased with increasing age among women without CIN; but, a bimodal age curve was observed among women with CIN. HPV 16 and 35 were the most common hrHPV genotypes in all age and CIN groups. HPV 45 became more frequent among older women with CIN grade 2 or 3 (CIN2,3). Younger women (17–29 years) had more multiple hrHPV genotypes overall and in each cervical disease group than older women (40–65 years).
HPV 16, 35, and 45 were the leading contributors to CIN 2,3. The current HPV vaccines could significantly reduce HPV-related cervical disease; however, next generation vaccines that include HPV 35 and 45 would further reduce cervical disease in this population.
Although it is recognised that some women experience pain or bleeding during a cervical cytology test, few studies have quantified physical after-effects of these tests.
To investigate the frequency, severity, and duration of after-effects in women undergoing follow-up cervical cytology tests, and to identify subgroups with higher frequencies in Grampian, Tayside, and Nottingham.
Cohort study nested with a multi-centre individually randomised controlled trial.
The cohort included 1120 women, aged 20–59 years, with low-grade abnormal cervical cytology who completed a baseline sociodemographic questionnaire and had a follow-up cervical cytology test in primary care 6 months later. Six weeks after this test, women completed a postal questionnaire on pain, bleeding, and discharge experienced after the test, including duration and severity. The adjusted prevalence of each after-effect was computed using logistic regression.
A total of 884 women (79%) completed the after-effects questionnaire; 30% of women experienced one or more after-effect: 15% reported pain, 16% bleeding, and 7% discharge. The duration of discharge was ≤2 days for 66%, 3–6 days for 22%, and ≥7 days for 11% of women. Pain or bleeding lasted ≤2 days in more than 80% of women. Severe after-effects were reported by <1% of women. The prevalence of pain decreased with increasing age. Bleeding was more frequent among nulliparous women. Discharge was more common among oral contraceptive users.
Pain, bleeding, and discharge are not uncommon in women having follow-up cervical cytology tests. Informing women about possible after-effects could better prepare them and provide reassurance, thereby minimising potential non-adherence with follow-up or non-participation with screening in the future.
after-effects; bleeding; complications; cervical smears; cytology; pain; primary care; vaginal discharge