Immune suppression and smoking history are risks for HPV-related anal disease in HIV-positive gay men

Prior infection with chlamydia a significant risk factor for infection with high-risk HPV types

Michael Carter
Published: 08 August 2013

Risk factors for human papillomavirus (HPV)-associated anal disease in HIV-positive gay men are similar to those already known to increase the risk of HPV-related cervical disease, research published in the online edition of the Journal of Infectious Diseases shows.

A low CD4 cell count and a history of infection with chlamydia were both associated with an increased risk of infection with high-risk HPV types and several smoking characteristics were associated with the presence of high-grade pre-cancerous anal lesions.

“Many of the significant risk factors found are similar to established risk factors for cervical HPV infection and cervical pre-cancer,” write the authors.

Anal cancer is rare in the general population and almost all cases are caused by persistent infection with high-risk HPV types. Rates of high-risk HPV are much higher in gay men living with HIV than other groups.

The history of anal cancer is very close to that of cervical cancer, which is also associated with HPV infection. A number of studies have identified the factors for the progression of HPV-associated cervical disease.

Investigators in California wanted to see which factors influenced the progression of HPV anal disease in HIV-positive men who have sex with men.

They therefore designed a cross-sectional study involving 305 men who had routine screening for HPV-associated anal disease between 2009 and 2010. 

The authors gathered lifestyle and clinical information and conducted a series of analyses to see which factors were associated with anal HPV infection and the presence of high-grade pre-cancerous lesions.

The men had a median age of 53 years (range, 47 to 60 years). The majority (94%) were taking antiretroviral therapy, 91% had a suppressed viral load (below 75 copies/ml) and 81% had a CD4 cell count above 350 cells/mm3.

Cytological tests showed that just over a fifth (21%) were negative for high-risk HPV types. Approximately 50% were infected with a high-risk HPV type without significant disease and 29% had pre-cancerous anal lesions.

Comparison between the men with pre-cancerous lesions and men without high-risk anal HPV infection showed that a CD4 cell count below 350 cells/mm3 (OR, 3.26; 95% CI, 1.122-8.74), a higher number – five and above – of lifetime male sexual partners (OR, 2.49; 95% CI, 1.12-5.58) and a history of chlamydia infection (OR, 4.46; 95% CI, 1.23-16.18) were all associated with an increased risk of pre-cancer. Smoking was also a risk factor.

Further comparison showed that a history of infection with chlamydia was also a risk factor for infection with high-risk HPV types (OR, 3.96; 95% CI, 1.13-13.90).

The investigators then controlled for confounding factors.

Previous infection with chlamydia was identified as an independent risk factor for infection with high-risk HPV types (OR, 4.24; 95% CI, 1.16-15.51). “It has been suggested that chlamydia may increase persistence of HPV in the cervix, but there is no evidence for a biological interaction,” note the authors. However, they suggest that a history of the infection is likely to be an indicator of sexual behaviour and could therefore be a surrogate marker “for increased exposure to HPV”.

A low CD4 cell count also increased the risk of infection with high-risk HPV types (OR, 3.96; 95% CI, 1.13-13.90). The investigators note that this confirms the findings of previous research showing that “low CD4 cell count (<350 cells/mm3) was strongly associated with carcinogenic HPV infection”.

Smoking was a risk factor for pre-cancerous lesions (2.71; 95% CI, 1.43-5.14).

This association was examined in a further model that controlled for other risk factors for high-risk HPV infection.

Comparison with men with high-risk strains of HPV but no significant disease showed that smoking in the past twelve months (OR, 3.20; 95% CI, 1.45-7.09), number of years smoked (over ten = OR, 3.09; 95% CI, 1.33-7.18), and number of packs smoked per day (over one = OR, 3.50; 95% CI, 1.19-10.28) were all associated with an increased risk of pre-cancerous lesions.

“Other studies have found smoking to be a risk factor for anal cancer,” comment the authors. “But our study is the first to demonstrate that smoking is a co-factor for anal pre-cancer, using rigorous histology-confirmed endpoints.” They call for more studies to assess the relationship between smoking and pre-cancerous lesions.

“We demonstrated that risk factors for HPV infection and progression to anal pre-cancer are similar to established risk factors for cervical cancer progression,” conclude the authors. “This could facilitate development of anal cancer early detection efforts, since established tools and approaches from cervical cancer screening can be adapted for a population at risk of anal cancer.”

Reference

Schwartz LM et al. Risk factors for anal HPV infection and anal precancer in HIV-infected men who have sex with men. J Infect Dis, online edition, 2013.

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