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Cervical cancer risk in women living with HIV across four continents: A multicohort study.

ABSTRACT: We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50?years vs. 16-30?years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/?l decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

SUBMITTER: Rohner E

PROVIDER: S-EPMC6898726 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Cervical cancer risk in women living with HIV across four continents: A multicohort study.

Rohner Eliane E Bütikofer Lukas L Schmidlin Kurt K Sengayi Mazvita M Maskew Mhairi M Giddy Janet J Taghavi Katayoun K Moore Richard D RD Goedert James J JJ Gill M John MJ Silverberg Michael J MJ D'Souza Gypsyamber G Patel Pragna P Castilho Jessica L JL Ross Jeremy J Sohn Annette A Bani-Sadr Firouze F Taylor Ninon N Paparizos Vassilios V Bonnet Fabrice F Verbon Annelies A Vehreschild Jörg Janne JJ Post Frank A FA Sabin Caroline C Mocroft Amanda A Dronda Fernando F Obel Niels N Grabar Sophie S Spagnuolo Vincenzo V Quiros-Roldan Eugenia E Mussini Cristina C Miro José M JM Meyer Laurence L Hasse Barbara B Konopnicki Deborah D Roca Bernardino B Barger Diana D Clifford Gary M GM Franceschi Silvia S Egger Matthias M Bohlius Julia J

International journal of cancer 20190619 3

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incid ...[more]

PMID: 31215037

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Project description:OBJECTIVE:We suggested cervical cancer screening strategies for women living with HIV (WLHIV) by comparing their precancer risks to general population women, and then compared our suggestions with current Centers for Disease Control and Prevention (CDC) guidelines. DESIGN:We compared risks of biopsy-confirmed cervical high-grade squamous intraepithelial neoplasia or worse (bHSIL+), calculated among WLHIV in the Women's Interagency HIV Study, to 'risk benchmarks' for specific management strategies in the general population. METHODS:We applied parametric survival models among 2423 WLHIV with negative or atypical squamous cell of undetermined significance (ASC-US) cytology during 2000-2015. Separately, we synthesized published general population bHSIL+ risks to generate 3-year risk benchmarks for a 3-year return (after negative cytology, i.e. 'rescreening threshold'), a 6-12-month return (after ASC-US), and immediate colposcopy [after low-grade squamous intraepithelial lesion (LSIL)]. RESULTS:Average 3-year bHSIL+ risks among general population women ('risk benchmarks') were 0.69% for a 3-year return (after negative cytology), 8.8% for a 6-12-month return (after ASC-US), and 14.4% for colposcopy (after LSIL). Most CDC guidelines for WLHIV were supported by comparing risks in WLHIV to these benchmarks, including a 3-year return with CD4 greater than 500 cells/?l and after either three negative cytology tests or a negative cytology/oncogenic human papillomavirus cotest (all 3-year risks?1.3%); a 1-year return after negative cytology with either positive oncogenic human papillomavirus cotest (1-year risk?=?1.0%) or CD4 cell count less than 500 cells/?l (1-year risk?=?1.1%); and a 6-12-month return after ASC-US (3-year risk?=?8.2% if CD4 cell count at least 500 cells/?l; 10.4% if CD4 cell count?=?350-499 cells/?l). Other suggestions differed modestly from current guidelines, including colposcopy (vs. 6-12 month return) for WLHIV with ASC-US and CD4 cell count less than 350 cells/?l (3-year risk?=?16.4%) and a lengthened 2-year (vs. 1-year) interval after negative cytology with CD4 cell count at least 500 cells/?l (2-year risk?=?0.98%). CONCLUSIONS:Current cervical cancer screening guidelines for WLHIV are largely appropriate. CD4 cell count may inform risk-tailored strategies.

Project description:BackgroundHigh-risk human papillomavirus HPV (HR-HPV) modifies cervical cancer risk in people living with HIV, yet African populations are under-represented. We aimed to compare the frequency, multiplicity and consanguinity of HR-HPVs in HIV-negative and HIV-positive Zimbabwean women.MethodsThis was a cross-sectional study consisting of women with histologically confirmed cervical cancer attending Parirenyatwa Group of Hospitals in Harare, Zimbabwe. Information on HIV status was also collected for comparative analysis. Genomic DNA was extracted from 258 formalin fixed paraffin embedded tumour tissue samples, and analysed for 14 HR-HPV genotypes. Data was analysed using Graphpad Prism and STATA.ResultsForty-five percent of the cohort was HIV-positive, with a median age of 51 (IQR = 42-62) years. HR-HPV positivity was detected in 96% of biospecimens analysed. HPV16 (48%), was the most prevalent genotype, followed by HPV35 (26%), HPV18 (25%), HPV58 (11%) and HPV33 (10%), irrespective of HIV status. One third of the cohort harboured a single HPV infection, and HPV16 (41%), HPV18 (21%) and HPV35 (21%) were the most prevalent. HIV status did not influence the prevalence and rate of multiple HPV infections (p>0.05). We reported significant (p<0.05) consanguinity of HPV16/18 (OR = 0.3; 95% CI = 0.1-0.9), HPV16/33 (OR = 0.3; 95% CI = 0.1-1.0), HPV16/35 (OR = 3.3; 95% CI = 2.0-6.0), HPV35/51 (OR = 6.0; 95%CI = 1.8-15.0); HPV39/51 (OR = 6.4; 95% CI = 1.8-15), HPV31/52 (OR = 6.2; 95% CI = 1.8-15), HPV39/56 (OR = 11 95% CI = 8-12), HPV59/68 (OR = 8.2; 95% CI = 5.3-12.4), HPV66/68 (OR = 7; 95% CI = 2.4-13.5), independent of age and HIV status.ConclusionWe found that HIV does not influence the frequency, multiplicity and consanguinity of HR-HPV in cervical cancer. For the first time, we report high prevalence of HPV35 among women with confirmed cervical cancer in Zimbabwe, providing additional evidence of HPV diversity in sub-Saharan Africa. The data obtained here probes the need for larger prospective studies to further elucidate HPV diversity and possibility of selective pressure on genotypes.

Project description:BackgroundThe interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes.MethodsWe did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I2 statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546).FindingsWe identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0·83, 95% CI 0·70-0·99; I2=51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0·65, 0·40-1·06; I2=30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0·59, 0·40-0·87; I2=0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0·64, 95% CI 0·54-0·75; I2=18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1·54, 1·30-1·82; I2=0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0·40, 95% CI 0·18-0·87, I2=33%).InterpretationEarly ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect.FundingUK Medical Research Council.

Dataset Information

Cervical cancer risk in women living with HIV across four continents: A multicohort study.

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Cervical cancer risk in women living with HIV across four continents: A multicohort study.

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