Anal HPV infection often involves multiple HPV strains in HIV-positive men

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A broad spectrum of HPV genotypes is present in the anuses of HIV-positive men, according to an Italian study published in the January 1st edition of the Journal of Acquired Immunodeficiency Syndromes. The study also showed that many men are infected with multiple HPV genotypes.

Infection with human papilloma virus (HPV) can cause anogenital cancers. HPV-16 and -18 are the strains of the virus that involve the greatest risk of cervical cancer, but a broad spectrum of HPV types has been associated with cancer development.

HIV-positive individuals, particularly if they have a suppressed immune system, are more likely to develop pre-cancerous or cancerous anogenital lesions.

Glossary

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

strain

A variant characterised by a specific genotype.

 

immune system

The body's mechanisms for fighting infections and eradicating dysfunctional cells.

invasive

In medical terms, going inside the body.

Italian investigators wished to determine the spectrum of HPV types present in HIV-positive men and the relationship between these HPV strains and cancerous or pre-cancerous anal lesions.

The study involved 253 HIV-positive men who were referred to a sexual health clinic in Milan. Most of these men 177 (70%) had acquired HIV through sex with another man. Cells were obtained from the men’s anuses and tests were conducted to determine the HPV types present. All the men had an anoscopy and biopsies were performed on any lesions.

Median age was 34 years, median CD4 cell count 468 cells/mm3 and median viral load 251 copies/ml. A total of 79% of the men were taking anti-HIV therapy.

A total of 233 anal samples were available for examination. Of these, 30 were HPV-negative. Of the remaining 203 samples, 199 were suitable for genotyping. A total of 30 different HPV genotypes were isolated. The most commonly isolated HPV genotypes were HPV-16, 85 samples, HPV-6, 63 samples, and HPV-30, 20 samples. HPV genotypes with a high risk of anal cancer were isolated from 58% of all the samples collected.

In all, 24 of the samples were negative for pre-cancerous lesions, 139 were associated with low-grade lesions, 32 with high-grade pre-cancerous lesions, and one sample was associated with invasive anal cancer.

No specific association between anal lesions and a single HPV genotype was identified. However infection with multiple HPV genotypes was present in 62% of cases. Two separate genotypes were isolated from 76 patients (38%), three genotypes from 32 patients (16%) and four or more genotypes were present in 13 patients (7%).

Patients with three or more HPV genotypes had significantly lower CD4 cell counts (p = 0.051) and significantly higher HIV viral loads (p = 0.042).

The risk of multiple infections was 22 times higher in patients with HPV-16 or -18 (OR, 22.24, 95% CI: 8.93 – 55.39), and six times greater in patients with other high risk HPV genotypes compared to those with lower risk HPV strains (OR, 6.42, 95% CI: 2.62 – 15.76).

The risk of multiple infections was also increased in patients with an HIV viral load above 5000 copies/ml (OR, 2.196, 95% CI: 0.99 – 4.86) or with a CD4 cell count below 200 cells/mm3 (OR, 4.85, 95% CI: 0.99 – 23.68). The lower a patient’s CD4 cell count, the higher their risk of multiple infections (p = 0.037).

Age was also associated with a risk of multiple infections. Patients aged under 30 were significantly more likely to have multiple infections compared to those aged between 30 – 50 (p < 0.01).

“The broad spectrum of HPV genotypes and the high prevalence of multiple infections found in this study are points of concern”, conclude the investigators. They call for large prospective studies to determine the disease progression risks associated with single and multiple HPV genotype infections. They add that studies are also needed to determine the clinical significance of rarer HPV genotypes and “the role of anti-HPV vaccination programmes in the general target population and/or special at-risk subgroups.”

References

Orlando G et al. Human papillomavirus genotypes and anal-related lesions among HIV-1-infected men in Milan, Italy. J Acquir Immune Defic Syndr 47: 129 – 131, 2008.