Mantoux test good predictor of HIV-positive women's response to HPV

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Skin prick testing may be better than CD4 counts as a way of measuring the ability of a HIV-positive woman’s immune system to tackle human papillomavirus (HPV) infection, according to a study published in the September edition of AIDS.

HPV infection is common in HIV-positive women, and infection with HIV increases the risk of a woman developing cancerous or pre-cancerous cervical cell changes.

Cutaneous anergy testing – or skin prick testing - evaluates the ability of the body to mount an specific type of immune response and reflects the number and the capacity of certain immune cells throughout the body, not just in the skin. The word anergy means a lack of reaction by the body's defence mechanisms when exposed to foreign substances (antigens).

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.

anergy

Lack of reaction by the body's defence mechanisms when foreign substances come into contact with the body. This may indicate the inability of the immune system to mount a normal allergic response.

cervix

The cervix is the neck of the womb, at the top of the vagina. This tight ‘collar’ of tissue closes off the womb except during childbirth. Cancerous changes are most likely in the transformation zone where the vaginal epithelium (lining) and the lining of the womb meet.

odds ratio (OR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

immune system

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

The most common test involves the Mantoux technique, where small amounts of antigens are injected just underneath the skin. The response is measured by how much the skin comes up in bumps - a hypersensitivity reaction as a result of the immune system attacking the antigen. Mantoux testing used to be used routinely to screen children for tuberculosis immunity by injecting a tiny amount of TB antigen and seeing if they responded.

Researchers in this new study used the Mantoux technique to measuring delayed-type hypersensitivity (DTH) immune responses in 1,029 HIV-negative and 272 HIV-positive women.

They injected three antigens under the skin – a yeast called Candida albicans, tetanus toxin and mumps – and measured the response. The women were also evaluated for the presence of HPV and cervical neoplasia and also had their CD4 counts and HIV loads measured.

Those women who had anergy - no DTH reaction to the skin prick test – were 70% more likely to have cervical neoplasia (odds ratio 1.70, 95% CI 1.16 to 2.48) and 24% more likely to be infected with a strain of HPV known to increase the risk of developing cancer (odds ratio 1.24, 95% CI 0.99 to 1.56). These figures were irrespective of CD4 count or presence of HIV.

The authors say these results suggest that anergy status provides information regarding immune control of HPV and cervical neoplasia not accounted for by CD4 and HIV levels in circulation.

Cutaneous anergy testing has the potential to be used in identifying those women at increased risk of HPV infection and cervical neoplasia and therefore cancer. But anergy testing for HPV would have to be greatly improved, possibly by evaluating the use of the virus itself as the stimulating antigen in the Mantoux test, they add.

They conclude that further research is needed to understand the functional deficiencies in DTH-related immune cells that correlate with HPV infection.

References

Harris TG et al. Association of cutaneous anergy with human papillomavirus and cervical neoplasia on HIV-seropositive and seronegative women. AIDS 21: 1933-1941, 2007.