Study suggests HPV16 can skirt the immune system
Human papillomavirus 16 (HPV16), the virus responsible for approximately half of all cervical cancers, appears to be better at dodging the immune system than other HPV types, according to a large study of HIV-positive women in the July 16 issue of the Journal of the National Cancer Institute. The findings may help explain why HPV16 plays such a major role in causing cervical cancer in the general population.
Whereas other HPV types have a lower prevalence and incidence among women with stronger immune systems (in theory, the stronger the immune system, the better it is at fighting off infections), researchers detected similar levels of HPV16 in women with both weak and strong immune systems.
More than 30 types of HPV are known to infect the genital epithelium. HPV16 has been the strain most strongly associated with cervical cancer and its precursor lesions. What sets HPV16 apart from other HPV types has not been clear. A preliminary analysis of a study on HPV infection among women positive for HIV, the virus that causes AIDS, suggested that HPV16 may be less associated with immune status than other HPV types.
To confirm this theory, Howard D. Strickler, M.D., and Robert D. Burk, M.D., of the Albert Einstein College of Medicine in Bronx, N.Y., and their colleagues compared the prevalence and incidence of different HPV types among HIV-positive women with varying levels of T cells, an indicator of immune status.
The final analysis included 2,058 HIV-positive women from the Women’s Interagency Human Immunodeficiency Virus Study and 871 HIV-positive women from a separate HIV Epidemiology Research Study. The women were examined during repeat study visits where cervical tissue samples were collected and HPV-type analysis was performed.
The researchers found that the prevalence ratio for HPV16, calculated by comparing prevalence rates of each HPV type for women with low versus high T-cell count, was low compared with that of other HPV types at every visit in both cohorts, suggesting that HPV16 is less influenced by the immune system than other HPV types.
In fact, the summary prevalence ratio for HPV16 was statistically significantly lower than that of all other HPV types combined. The incidence of HPV16 was also less associated with T-cell count than the incidence of other HPV types.
"The predominance of HPV16 in cervical disease in the general population might be explained partly by its ability to avoid immune clearance and the effects that this avoidance might have on the frequency and duration of infection," the authors write.
They say that the results of this study raise a number of testable hypotheses. "If it is true that the major etiologic risk factor for cervical cancer, HPV16, is not strongly affected by immune status, this fact could also help explain why cervical cancer rates appear to be only moderately increased in HIV/AIDS-affected women compared with HIV-seronegative women," they write.
Similarly, the use of highly active antiretroviral therapy (HAART) to improve immune status might only have a moderate effect on lowering an HIV-positive woman’s risk of developing precancerous lesions and cervical cancer. "We predict that the use of HAART in HIV-seropositive women will reduce the incidence, duration, and progression of cervical lesions, but that its effect will be less on lesions related to HPV16 than on those related to other HPV types," the authors say.
They add that additional studies should be able to address these predictions.
Albert Einstein College of Medicine
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Linda Wang | EurekAlert!