Multiple High-Risk HPV Types Contribute to Cervical Dysplasia in Ugandan Women Living With HIV on Antiretroviral Therapy.
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
received:
02
08
2021
accepted:
02
02
2022
pubmed:
24
2
2022
medline:
18
6
2022
entrez:
23
2
2022
Statut:
ppublish
Résumé
Cervical cancer mortality remains high in sub-Saharan Africa, especially among women living with HIV (WLWH). Characterization of prevalent high-risk human papillomavirus (hrHPV) types and immune function in WLWH with cervical abnormalities despite antiretroviral therapy (ART) can inform prevention strategies. Kampala, Uganda. From 2017 to 2020, we enrolled Ugandan women with cervical dysplasia detected with visual inspection with acetic acid (VIA). WLWH were required to be on ART >3 months with plasma HIV RNA <1000 copies/mL. Biopsies from VIA-positive lesions underwent histopathologic grading and cervical swab specimens were tested for hrHPV. Clinical correlations were evaluated with Poisson regression to estimate adjusted prevalence ratios (aPR). One hundred eighty-eight WLWH and 116 HIV-seronegative women participated. Among WLWH, median ART duration was 6 years and median CD4 667 cells/µL. Cervical intraepithelial neoplasia (CIN) grade 2/3 was found in 29% of WLWH versus 9% of HIV-seronegative women. In women with CIN1 or without histopathology-confirmed dysplasia, hrHPV (aPR [95% confidence interval]: 2.17 [1.43 to 3.29]) and multiple hrHPV (aPR 3.73 [1.07 to 13.1]) were more common in WLWH, as were vaccine-targeted and vaccine-untargeted hrHPVtypes. Differences in hrHPV prevalence by HIV serostatus were not observed in women with CIN2/3 (interaction P < 0.01). Among WLWH, low CD4/8 ratio was associated with hrHPV while detectable plasma HIV RNA (20-1000 copies/mL) was associated with CIN2/3 or invasive cancer. Despite ART, WLWH with cervical VIA abnormalities remain at elevated risk for multiple hrHPV and high-grade dysplasia. Cervical cancer prevention and research tailored for WLWH are warranted in the ART era.
Sections du résumé
BACKGROUND
Cervical cancer mortality remains high in sub-Saharan Africa, especially among women living with HIV (WLWH). Characterization of prevalent high-risk human papillomavirus (hrHPV) types and immune function in WLWH with cervical abnormalities despite antiretroviral therapy (ART) can inform prevention strategies.
SETTING
Kampala, Uganda.
METHODS
From 2017 to 2020, we enrolled Ugandan women with cervical dysplasia detected with visual inspection with acetic acid (VIA). WLWH were required to be on ART >3 months with plasma HIV RNA <1000 copies/mL. Biopsies from VIA-positive lesions underwent histopathologic grading and cervical swab specimens were tested for hrHPV. Clinical correlations were evaluated with Poisson regression to estimate adjusted prevalence ratios (aPR).
RESULTS
One hundred eighty-eight WLWH and 116 HIV-seronegative women participated. Among WLWH, median ART duration was 6 years and median CD4 667 cells/µL. Cervical intraepithelial neoplasia (CIN) grade 2/3 was found in 29% of WLWH versus 9% of HIV-seronegative women. In women with CIN1 or without histopathology-confirmed dysplasia, hrHPV (aPR [95% confidence interval]: 2.17 [1.43 to 3.29]) and multiple hrHPV (aPR 3.73 [1.07 to 13.1]) were more common in WLWH, as were vaccine-targeted and vaccine-untargeted hrHPVtypes. Differences in hrHPV prevalence by HIV serostatus were not observed in women with CIN2/3 (interaction P < 0.01). Among WLWH, low CD4/8 ratio was associated with hrHPV while detectable plasma HIV RNA (20-1000 copies/mL) was associated with CIN2/3 or invasive cancer.
CONCLUSION
Despite ART, WLWH with cervical VIA abnormalities remain at elevated risk for multiple hrHPV and high-grade dysplasia. Cervical cancer prevention and research tailored for WLWH are warranted in the ART era.
Identifiants
pubmed: 35195571
doi: 10.1097/QAI.0000000000002941
pii: 00126334-202207010-00012
pmc: PMC9203909
mid: NIHMS1781266
doi:
Substances chimiques
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
333-342Subventions
Organisme : NIAID NIH HHS
ID : P30 AI027757
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206466
Pays : United States
Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
S.V.A., A.T., J.O. and T.S.U. received support from Hoffman LaRoche for investigator-initiated research. T.S.U. received research support from Merck and Celgene/BMS for investigator-initiated research and consults for AbbVie and Seattle Genetics. T.S.U. is currently an employee at Regeneron. C.C. is a member of the scientific advisory boards of Viracta Therapeutics and Curevo Vaccines, receives research support from Celularity, Inc., and is a consultant for EUSA Pharma. The remaining authors have no conflicts of interest to disclose.
Références
de Martel C, Plummer M, Vignat J, et al. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141:664–670.
Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health. 2021;9:e161–e169.
Johnson LF, Mossong J, Dorrington RE, et al. Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies. PLoS Med. 2013;10:e1001418.
Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017;4:e349–e356.
Banura C, Mirembe FM, Katahoire AR, et al. Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: a systematic review. Infect Agent Cancer. 2011;6:11.
Nakalembe M, Makanga P, Mubiru F, et al. Prevalence, correlates, and predictive value of high-risk human papillomavirus mRNA detection in a community-based cervical cancer screening program in western Uganda. Infect Agent Cancer. 2019;14:14.
Nakisige C, Schwartz M, Ndira AO. Cervical cancer screening and treatment in Uganda. Gynecol Oncol Rep. 2017;20:37–40.
Gulland A. Uganda launches HPV vaccination programme to fight its commonest cancer. BMJ. 2012;345:e6055.
Banura C, Mirembe FM, Katahoire AR, et al. Universal routine HPV vaccination for young girls in Uganda: a review of opportunities and potential obstacles. Infect Agent Cancer. 2012;7:24.
Bruni L, Albero G, Serrano B, et al. Human papillomavirus and related diseases in the World. ICO/IARC Information Centre on HPV and Cancer. Summary Report June 17, 2019. https://hpvcentre.net/statistics/reports/XWX.pdf . Accessed August 10, 2020.
Isabirye A, Mbonye M, Asiimwe JB, et al. Factors associated with HPV vaccination uptake in Uganda: a multi-level analysis. BMC Womens Health. 2020;20:145.
Looker KJ, Ronn MM, Brock PM, et al. Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): systematic reviews and meta-analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status. J Int AIDS Soc. 2018;21:e25110.
Bruni L, Diaz M, Castellsague X, et al. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis. 2010;202:1789–1799.
Clifford GM, de Vuyst H, Tenet V, et al. Effect of HIV infection on human papillomavirus types causing invasive cervical cancer in Africa. J Acquir Immune Defic Syndr. 2016;73:332–339.
Davy-Mendez T, Napravnik S, Zakharova O, et al. Acute HIV infection and CD4/CD8 ratio normalization after antiretroviral therapy initiation. J Acquir Immune Defic Syndr. 2018;79:510–518.
Ferris DG, Greenberg MD. Reid's colposcopic index. J Fam Pract. 1994;39:65–70.
de Villiers EM, Fauquet C, Broker TR, et al. Classification of papillomaviruses. Virology. 2004;324:17–27.
Carozzi F, Puliti D, Ocello C, et al. Monitoring vaccine and non-vaccine HPV type prevalence in the post-vaccination era in women living in the Basilicata region, Italy. BMC Infect Dis. 2018;18:38.
Fleiss JL, Levin B, Paik MC. Statistical Methods for Rates and Proportions. 3rd ed. Hoboken, NJ: J. Wiley; 2003.
Ogembo RK, Gona PN, Seymour AJ, et al. Prevalence of human papillomavirus genotypes among African women with normal cervical cytology and neoplasia: a systematic review and meta-analysis. PLoS One. 2015;10:e0122488.
De Vuyst H, Mugo NR, Chung MH, et al. Prevalence and determinants of human papillomavirus infection and cervical lesions in HIV-positive women in Kenya. Br J Cancer. 2012;107:1624–1630.
Visual inspection with acetic acid for cervical-cancer screening: test qualities in a primary-care setting. University of Zimbabwe/JHPIEGO Cervical Cancer Project. Lancet. 1999;353:869–873.
Bansil P, Lim J, Byamugisha J, et al. Performance of cervical cancer screening techniques in HIV-infected women in Uganda. J Low Genit Tract Dis. 2015;19:215–219.
Jeronimo J, Bansil P, Lim J, et al. A multicountry evaluation of careHPV testing, visual inspection with acetic acid, and papanicolaou testing for the detection of cervical cancer. Int J Gynecol Cancer. 2014;24:576–585.
Chung MH, McKenzie KP, De Vuyst H, et al. Comparing Papanicolau smear, visual inspection with acetic acid and human papillomavirus cervical cancer screening methods among HIV-positive women by immune status and antiretroviral therapy. AIDS. 2013;27:2909–2919.
Kafuruki L, Rambau PF, Massinde A, et al. Prevalence and predictors of cervical intraepithelial neoplasia among HIV infected women at Bugando Medical Centre, Mwanza-Tanzania. Infect Agent Cancer. 2013;8:45.
Parham GP, Mwanahamuntu MH, Kapambwe S, et al. 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. PLoS One. 2015;10:e0122169.
Jeronimo J, Castle PE, Temin S, et al. Secondary prevention of cervical cancer: ASCO resource-stratified clinical practice guideline. JCO Glob Oncol. 2017;3:635–657.
Nakisige C, Trawin J, Mitchell-Foster S, et al. Integrated cervical cancer screening in Mayuge District Uganda (ASPIRE Mayuge): a pragmatic sequential cluster randomized trial protocol. BMC Public Health. 2020;20:142.
Sigel K, Wisnivesky J, Crothers K, et al. Immunological and infectious risk factors for lung cancer in US veterans with HIV: a longitudinal cohort study. Lancet HIV. 2017;4:e67–e73.