Where are we heading with the horrible interaction between human papillomavirus (HPV) and HIV?

Editor’s notes: Human papillomavirus (HPV) is the most common sexually transmitted infection in the world.  There are over 200 different strains of HPV, distinguished by genetic typing.  The strains are classified into high-risk and low-risk based on their associations with the development of cervical cancer, but also genital warts and anal cancer.  HPV16 is the most common high-risk strain and is found in about half of cervical cancers and 70% of anal cancers.  Although anal cancer is much less common than cervical cancer among women, there is clear evidence that women living with HIV are at greater risk not only of cervical cancer but also of anal cancer.

In a study in Vitoria, Brazil, Volpini and colleagues collected cervical and anal samples from 126 women living with HIV who had recently had a normal Pap smear, and so did not already have pre-cancerous lesions in the cervix.  They found DNA from HPV in 71% of the women. 39% of women had HPV in cervical samples, while 60% had HPV in anal samples.

HPV16 was the most prevalent type at the cervical and anal sites (9% and 18%, respectively).  Other high risk strains were found in the cervical samples from more than 30% of women and in the anal samples of another 12% of women (some women had multiple strains). All currently available vaccines protect against HPV16 and one also protects against HPV45 and 31 (which accounted for almost half of the remaining high risk strains from the cervical samples).  The vaccine works best when given before any HPV infection, and is therefore recommended for girls before they become sexually active.  However, persistence and clearance of HPV is a dynamic process and the possible benefits of vaccination in those already infected are not yet clear.

Testing for HPV is becoming increasingly sophisticated, with molecular technology becoming available that allows detection of DNA and strain typing.  It seems very probable that women living with HIV with high-risk strains in either cervical or anal samples are at greater risk of developing cancer and therefore need additional more intense screening to detect and treat any pre-cancerous abnormalities in their epithelium prior to the development of invasive cancers.  Current guidelines already recommend that women living with HIV are offered Pap smears more regularly than their HIV-negative peers.  DNA based technology may make it possible to offer a more targeted approach to women at the most risk.

In the meantime, encouraging HPV vaccination among schoolgirls (and eventually boys too) is a long term prevention measure.  Ensuring that HPV screening services and HIV prevention and care services are well co-ordinated or even integrated is something that will have an immediate impact on preventing deaths from cervical cancer.  Incorporating molecular testing might help us to reduce the incidence of anal cancer too.

The high prevalence of HPV and HPV16 European variants in cervical and anal samples of HIV-seropositive women with normal Pap test results.

Volpini LPB, Boldrini NAT, de Freitas LB, Miranda AE, Spano LC. PLoS One. 2017 Apr 20;12(4):e0176422. doi: 10.1371/journal.pone.0176422. eCollection 2017.

Human immunodeficiency virus (HIV)-seropositive women are more likely to have anogenital cancer, and high risk-HPV (HR-HPV) infection is the main associated factor. Between August 2013 and December 2015, we conducted a descriptive study to determine the HPV genotypes and HPV16 variants in cervical and anal samples of HIV-seropositive women with a normal Pap test. The viral DNA was amplified by PCR using the PGMY09/11 set of primers. Reverse line blot (RLB), restriction fragment length polymorphism (RFLP) and sequencing assays were used to determine the HPV genotypes. HPV16 variants were identified by gene sequencing. We found a high frequency of HR-HPV (60.3%; 76/126) at the anogenital site among HIV-seropositive women and without association with anal intercourse. HPV16 and European variant predominated among the HR-HPV. Mixed infections with at least three different HPV types were common, particularly at the anal site. CD4+ T-cell counts below 500 cells/mm3, a HIV viral load above 50 copies/mL and an age of 18 to 35 years old were all related to HPV anal infection. Our study showed a high frequency of HR-HPV in both cervical and anal sites of women with negative cytology belonging to a risk group for the development of anogenital cancer.

Abstract [1] Full-text [free] access  [2]

Cancers [4], Comorbidity [5]
Europe [6]
Brazil [7]
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