Prevalence of cervical, oral, and anal human papillomavirus infection in women living with HIV in Denmark – The SHADE cohort study
Section snippets
Background
Five percent of the world’s cancer burden is attributable to human papillomavirus (HPV) infection [1], and people living with HIV (PLWH) have elevated risk of HPV related cancers at different anatomical sites, compared to their HIV-negative peers [2], [3], [4]. Especially increased risk of HPV-related cervical cancer (CC) [2], [5], [6], [7], [8], [9], oropharyngeal cancer (OPC) [5], [10], [11], and anal cancer (AC) [5], [12] has been reported [2], [5], [6], [7], [8], [9]. Whereas HPV is the
Objectives
The aim of the present study was to assess the prevalence, distribution and concordance of cervical, oral, and anal HPV in WLWH in Denmark. Furthermore, we aimed at identifying predictors of oral and anal HPV.
Setting
Denmark has a population of 5.7 million [29] and an estimated HIV prevalence among adults of 0.1% [30]. Medical care, including ART, is tax-paid and provided free-of-charge to all PLWH [22]. Treatment of HIV is restricted to eight specialized medical centres. Six of these centres participated in the SHADE [22]. PLWH are visiting outpatient clinics at intended intervals of 3–6 months [31]. During the study period, HIV guidelines recommended cervical cytology twice the first year after HIV
Characteristics of the cohort
A total of 334 WLWH consented for study participation [22]. Of 326 cervical, 327 oral and 327 anal samples; 295 (90.5%), 273 (83.5%) and 270 (82.6%) yielded sufficient DNA for HPV assessment, leaving 214 (64.1%) participants with conclusive HPV test results from all three anatomical sites. Baseline characteristics of the 214 included WLWH are presented in Table 1. Median age at inclusion was 42.9 years (IQR 36.3–48.4) and median duration of HIV was 11.0 years (IQR 5.3–17.1). Overall, 95.3% of
Discussion
In this multicentre, cross-sectional cohort study of WLWH in Denmark, more than half of WLWH were concurrently cervical and anal HPV positive, and a large proportion presented with multiple anogenital HPV infections. A correlation between cervical and anal hr- and lrHPV was observed and cervical HPV infection predicted anal HPV infection. Non-16/18 hrHPV genotypes were predominant at all anatomical sites. Almost half the present hrHPV genotypes would have been covered by the 9-valent HPV
Conclusion
Systematically generated evidence of HPV infection in cohorts of PLWH can help shape primary and secondary HPV related cancer prevention. Here we present data from a Danish cohort of WLWH, demonstrating that more than half had cervical and anal HPV infection with a large proportion presenting with multiple, concurrent anogenital HPV infections. Non-16/18 hrHPV genotypes were predominant, which renders the 2- and 4-valent HPV vaccines less effective than the 9-valent HPV vaccine. Regarding
Authors’ contributions
KT contributed to conception and design of the study, included patients, performed interviews and gynaecological examinations, analysed and interpreted data, and drafted the manuscript. MS contributed to conception and design of the study, included patients, performed interviews and gynaecological examinations, and critically reviewed the manuscript. TLK contributed to conception and design of the study, included patients, performed interviews and gynaecological examinations, and critically
Funding
This work was supported by the Danish Cancer Society and the AIDS Foundation; the Aragon Foundation; the Foundation of Aase and Ejnar Danielsens and the Foundation of Anna and Preben Simonsen. Grant numbers do not apply in a Danish setting. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation or writing of the article.
Ethical approval
The study and the DHCS were approved by the Danish Data Protection Agency (2015-231-0126, 2012-58-0004 and 2012-41-0005). The study was approved by the Danish Regional Committee on Health Research Ethics (approval numbers: H-3-2010-119 and H-2-2014-102).
Conflict of interests
KT has received research funding from Abbott, a travel grant from Janssen-Cilag and honoraria from Janssen-Cilag, BMS and GlaxoSmithKline/Viiv. MS has received an unrestricted grant from Gilead. TLK has received research funding and/or honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, GlaxoSmithKline/Viiv, Abbott, Gilead, and Janssen-Cilag. Since the paper in question was initiated, SL, has taken up a position in Novo Nordisk A/S working within the insulin franchise. For this paper SL
Acknowledgements
We are first and foremost grateful to all the women living with HIV for participating in the study. We further thank the staff of our clinical departments for their continuous support and enthusiasm at the participating centres in the SHADE cohort: Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre (K Thorsteinsson); Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet (AM Lebech, TL Katzenstein, FF Rönsholt); Department of Infectious
References (59)
- et al.
Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis
Lancet
(2007) - et al.
III: Women with HIV are more commonly infected with non-16 and −18 high-risk HPV types
Gynecol. Oncol.
(2010) - et al.
Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: a systematic review and meta-analysis
Lancet Infect. Dis.
(2018) - et al.
HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus
Virology
(2013) - et al.
Human Papillomavirus infection and cervical lesions in HIV infected women on antiretroviral treatment in Thailand
J. Infect.
(2017) - et al.
Prevalence of anal human papillomavirus infection and anal HPV-related disorders in women: a systematic review
Am. J. Obstet. Gynecol.
(2015) - et al.
Chapter 2: the burden of HPV-related cancers
Vaccine
(2006) - et al.
Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era
Curr. HIV/AIDS Rep.
(2015) - et al.
The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature
BMC Infect. Dis.
(2016) Human papillomavirus-related disease in people with HIV
Curr. Opin. HIV AIDS
(2009)
Risk of human papillomavirus-associated cancers among persons with AIDS
J. Natl. Cancer Inst.
Risk factors for cervical HPV infection and genotypes distribution in HIV-infected South Brazilian women
Infect. Agents Cancer
Incidence and progression of cervical lesions in women with HIV: a systematic global review
Int. J. STD AIDS
Head and neck cancer in HIV patients and their parents: a Danish cohort study
Clin Epidemiol
Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era: 1997–2012
AIDS
Anal carcinoma in HIV-infected patients in the period 1995–2009: a Danish nationwide cohort study
Scand. J. Infect. Dis.
Epidemiology of human papillomavirus-Positive head and neck squamous cell carcinoma
J. Clin. Oncol.
Human papillomavirus-related oropharyngeal cancer in the HIV-infected population
Oral Dis.
On the etiology of anal squamous carcinoma
Dan. Med. Bull.
Prevalence and distribution of cervical high-risk human papillomavirus and cytological abnormalities in women living with HIV in Denmark – the SHADE
BMC Cancer
High-risk human papillomavirus genotypes distribution in a cohort of HIV-positive women living in Europe: epidemiological implication for vaccination against human papillomavirus
AIDS
Concomitant anal and cervical human papillomavirusV infections and intraepithelial neoplasia in HIV-infected and uninfected women
AIDS
Prevalence and distribution of cervical high-risk human papillomavirus and cytological abnormalities in women living with HIV in Denmark − the SHADE
BMC Cancer
Prevalence of and risk factors for anal oncogenic human papillomavirus infection among HIV-infected women in France in the combination antiretroviral therapy era
J. Infect. Dis.
Human papilloma virus types in the oral and cervical mucosa of HIV-positive South African women prior to antiretroviral therapy
J. Oral Pathol. Med.
Cervical and oral human papillomavirus types in HIV-1 positive and negative women with cervical disease in South Africa
J. Med. Virol.
Prevalence of genital, oral, and anal HPV infection among STI patients in Italy
J. Med. Virol.
Human papillomavirus at multiple sites associated with anal squamous intraepithelial lesions in HIV-Seropositive individuals
Ann. Clin. Cytol. Pathol.
Prevalence and Concordance of Human Papillomavirus Infection at Multiple Anatomic Sites Among HIV-infected Women from Chennai, India
Int. J. STD AIDS
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2022, Journal of the American Society of CytopathologyCitation Excerpt :Because of the design of the Cobas 4800 system, we were unable to further delineate the genotypic distribution for the patients who tested positive for ohrHPV. A recent study reported that HPV51 and HPV58, followed by HPV16 and HPV18, were the most prevalent hrHPV serotypes identified in a cohort of 214 women living with HIV in Denmark.20 In another study, HPV51 and HPV16 were reported as the most frequent anal hrHPV serotypes identified among 151 women living with HIV in Montreal, Quebec, Canada, with an infection rate of 29% and 31%, respectively.21
Oral and laryngeal HPV infection: Incidence, prevalence and risk factors, with special regard to concurrent infection in head, neck and genitals
2021, VaccineCitation Excerpt :Low oral HPV viral copy numbers might be missed depending on the sensitivity of the assay.[22] The ability to estimate rates of HPV type-specific acquisition and clearance is limited by the rarity of oral HPV infection.[23] Standardizing methods of oral sample collection and HPV detection would ensure comparability between future oral HPV studies.[24]
Sexually transmitted infections among women living with HIV in a Brazilian city
2021, Brazilian Journal of Infectious DiseasesCitation Excerpt :The prevalence of CIN lesions (18.5%) among WLHIV in this study was very similar to that reported in a study in HIV-negative women at a colposcopy clinic in Brazil (18.2%).14 However, the prevalence of CIN among women who reported more than 50 partners over their lifetime in our study was significantly higher (33%), and even higher than women with CD4 < 200/mm³ (42%), although HIV-associated immunosuppression is known to alter the relative carcinogenicity of HR-HPV types.27 A high prevalence of prior STIs (59.2%) was found in this study at a rate similar to that found in a study in the city of São Paulo, Brazil, in which the prevalence of was STIs around 61% in a group of women living with AIDS.12