Prevalence of cervical, oral, and anal human papillomavirus infection in women living with HIV in Denmark – The SHADE cohort study

doi:10.1016/j.jcv.2018.05.010

Journal of Clinical Virology

Volume 105, August 2018, Pages 64-71

https://doi.org/10.1016/j.jcv.2018.05.010 Get rights and content

Highlights

•
Cervical and anal HPV infection is highly prevalent in women living with HIV.
•
Anal HPV infection is associated with cervical HPV infection.
•
Non-16/18 hrHPV genotypes were predominant at all anatomical sites.
•
Half of hrHPV infections could have been prevented by the 9-valent HPV vaccine.

Abstract

Background

Women living with HIV (WLWH) have elevated risk of human papillomavirus (HPV) related cancers.

Objectives

To assess prevalence, distribution and concordance of cervical, oral, and anal HPV infection, and predictors of oral and anal HPV in WLWH in Denmark.

Study design

WLWH followed in the Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) were enrolled and examined for cervical, oral, and anal HPV infection. Logistic regression models were used to identify predictors of anal and oral HPV.

Results

A total of 214 of 334 WLWH had sufficient DNA for analysis at all three anatomical sites and were included in analyses. Cervical, oral, and anal high-risk (hr) HPV prevalence were 28.0%, 3.7% and 39.3%. Most frequent i) cervical, ii) oral and iii) anal hrHPV genotypes were i) hrHPV58 (8.4%), 52 (5.1%), 16 (5.1%) and 51 (5.1%); ii) 52 (1.4%) and iii) 51 (9.3%), 58 (8.9%), 16 (7.0%) and 18 (7.0%). Among present cervical, oral, and anal hrHPV genotypes, 6.7%, 12.5% and 17.9% were targeted by the 2-or 4-valent HPV vaccines, whereas 50.0%, 50.0% and 42.9% of hrHPV genotypes were covered by the 9-valent HPV vaccine. Anal HPV infection was predicted by cervical HPV infection (adjusted OR 4.47 (95%CI 2.25–8.89)).

Conclusion

Cervical and anal HPV infection were highly prevalent in WLWH. Non-16/18 hrHPV genotypes were predominant at all anatomical sites. Almost half of all hrHPV infections at the three anatomical sites could have been prevented by childhood/adolescent vaccination with the 9-valent HPV vaccine.

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)

A.E. Grulich et al.
Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis
Lancet
(2007)
N.D. McKenzie et al.
III: Women with HIV are more commonly infected with non-16 and −18 high-risk HPV types
Gynecol. Oncol.
(2010)
C. Lin 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)
S.M. Tugizov et al.
HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus
Virology
(2013)
T. Delory et al.
Human Papillomavirus infection and cervical lesions in HIV infected women on antiretroviral treatment in Thailand
J. Infect.
(2017)
E.A. Stier et al.
Prevalence of anal human papillomavirus infection and anal HPV-related disorders in women: a systematic review
Am. J. Obstet. Gynecol.
(2015)
D.M. Parkin et al.
Chapter 2: the burden of HPV-related cancers
Vaccine
(2006)
C. Brickman et al.
Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era
Curr. HIV/AIDS Rep.
(2015)
S. Taylor et al.
The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature
BMC Infect. Dis.
(2016)
J. Palefsky
Human papillomavirus-related disease in people with HIV
Curr. Opin. HIV AIDS
(2009)

A.K. Chaturvedi et al.

Risk of human papillomavirus-associated cancers among persons with AIDS

J. Natl. Cancer Inst.

(2009)

S.C. Rocha-Brischiliari et al.

Risk factors for cervical HPV infection and genotypes distribution in HIV-infected South Brazilian women

Infect. Agents Cancer

(2014)

S.A. Denslow et al.

Incidence and progression of cervical lesions in women with HIV: a systematic global review

Int. J. STD AIDS

(2014)

F.N. Engsig et al.

Head and neck cancer in HIV patients and their parents: a Danish cohort study

Clin Epidemiol

(2011)

L.S. Park et al.

Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era: 1997–2012

AIDS

(2016)

R. Legarth et al.

Anal carcinoma in HIV-infected patients in the period 1995–2009: a Danish nationwide cohort study

Scand. J. Infect. Dis.

(2013)

M.L. Gillison et al.

Epidemiology of human papillomavirus-Positive head and neck squamous cell carcinoma

J. Clin. Oncol.

(2015)

C.C. Wang et al.

Human papillomavirus-related oropharyngeal cancer in the HIV-infected population

Oral Dis.

(2016)

M. Frisch

On the etiology of anal squamous carcinoma

Dan. Med. Bull.

(2002)

K. Thorsteinsson et al.

Prevalence and distribution of cervical high-risk human papillomavirus and cytological abnormalities in women living with HIV in Denmark – the SHADE

BMC Cancer

(2016)

D. Konopnicki et al.

High-risk human papillomavirus genotypes distribution in a cohort of HIV-positive women living in Europe: epidemiological implication for vaccination against human papillomavirus

AIDS

(2016)

N.A. Hessol et al.

Concomitant anal and cervical human papillomavirusV infections and intraepithelial neoplasia in HIV-infected and uninfected women

AIDS

(2013)

K. Thorsteinsson et al.

Prevalence and distribution of cervical high-risk human papillomavirus and cytological abnormalities in women living with HIV in Denmark − the SHADE

BMC Cancer

(2016)

I. Heard et al.

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.

(2016)

K.L. Richter et al.

Human papilloma virus types in the oral and cervical mucosa of HIV-positive South African women prior to antiretroviral therapy

J. Oral Pathol. Med.

(2008)

D.J. Marais et al.

Cervical and oral human papillomavirus types in HIV-1 positive and negative women with cervical disease in South Africa

J. Med. Virol.

(2008)

G. Ciccarese et al.

Prevalence of genital, oral, and anal HPV infection among STI patients in Italy

J. Med. Virol.

(2017)

E. Chuang et al.

Human papillomavirus at multiple sites associated with anal squamous intraepithelial lesions in HIV-Seropositive individuals

Ann. Clin. Cytol. Pathol.

(2016)

L.J. Menezes et al.

Prevalence and Concordance of Human Papillomavirus Infection at Multiple Anatomic Sites Among HIV-infected Women from Chennai, India

Int. J. STD AIDS

(2016)

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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
Although anal cancer is more common in women, most of the studies on the role of high-risk human papillomavirus (hrHPV) infection in anal squamous lesions have focused on high-risk male patients. Therefore, we compared the genotype profile and clinicopathologic correlation of hrHPV infection in human immunodeficiency virus-positive (HIV+) men and women.
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Compared with the HIV+ men, the HIV+ women had a significantly lower rate of hrHPV infection (67.5% versus 78.5%; P < 0.0001) but a significantly higher rate of high-grade squamous intraepithelial lesions (HSILs) on anal Papanicolaou tests (4.6% versus 2.5%; P < 0.05). Other high-risk HPV (ohrHPV), as a group, is much more common than HPV16 or HPV18 in both genders. HIV+ women had significantly lower HPV16 and ohrHPV infection rates than did HIV+ men. However, the HPV18 infection rates were similar between HIV+ women and HIV+ men. For both genders, the rates of HSILs or high-grade anal intraepithelial neoplasia (AIN2-3) were significantly increased when coinfection of ohrHPV with either HPV16 or HPV18 was present.
Although both HIV+ men and HIV+ women have an increased risk of hrHPV infection, HIV+ women have different hrHPV genotype profiles and higher rates of high-grade lesions. Coinfection with different genotypes of hrHPV can significantly increase the risk of HSILs or AIN2-3 in both genders and could requires vigilant clinical and laboratory follow-up.
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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]
This review focuses on the importance of oral and laryngeal HPV infection which is present in majority of sexually active individuals at least once in their lifetime. Despite testing, still little is known about prevalence rates, determinants and, especially, the concurrent HPV infection in head and neck, and genitals. The purpose of this review is to clarify some issues of oral HPV incidence, prevalence, and to demonstrate the difficulties in identification of asymptomatic oral HPV carriers. The main premise to take up this topic is the high and still increasing risk for development of oropharyngeal cancer, and potential benefit from screening strategies, education programs and HPV vaccination.
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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
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In this study, 59% of women had at least one diagnosed STI at the time of the first clinic visit; 31% had clinical forms of anogenital HPV, 10% syphilis, 8%Neisseria gonorrhoeae, 5.0% trichomoniasis, 3% Chlamydia trachomatis, 1% hepatitis B, and 1% hepatitis C; 6.7% of the women presented with cervical cytological abnormalities. Furthermore, 46.3% of women had HR-HPV, and 17.6% had HPV 16/18. Only 5% of the women had a CD4 count <200 cells/mm³, 61.6% had undetectable HIV viral load, and 81.3% were currently on HAART.
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View full text

Prevalence of cervical, oral, and anal human papillomavirus infection in women living with HIV in Denmark – The SHADE cohort study

Highlights

Abstract

Background

Objectives

Study design

Results

Conclusion

Section snippets

Background

Objectives

Setting

Characteristics of the cohort

Discussion

Conclusion

Authors’ contributions

Funding

Ethical approval

Conflict of interests

Acknowledgements

Lancet

Gynecol. Oncol.

Lancet Infect. Dis.

Virology

J. Infect.

Am. J. Obstet. Gynecol.

Chapter 2: the burden of HPV-related cancers

Vaccine

Human papillomavirus in the HIV-infected host: epidemiology and pathogenesis in the antiretroviral era

Curr. HIV/AIDS Rep.

The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature

BMC Infect. Dis.

Human papillomavirus-related disease in people with HIV

Curr. Opin. HIV AIDS

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