Wednesday, October 7, 2009

Abnormal anal cells and high-risk HPV common in HIV-positive Australians

Over two-thirds of HIV-positive patients in an Australian cohort had abnormal cells in the anus, and 84% had anal infection with strains of human papilloma virus (HPV) that are associated with a high risk of anal cancer, according to an Australian study published in the April edition of Sexually Transmitted Infections. The investigators found that infection with high risk HPV was associated with the presence of high-grade pre-cancerous cells and pre-cancerous cells of undetermined, but potentially high-grade, significance. Anal cancer is a serious condition associated with high rates of illness and death. The prevalence of anal cancer amongst gay men is thought to be similar to that amongst women before screening for cervical cancer was introduced (approximately 35 cases per 100,000). Higher rates of anal cancer have been observed in HIV-positive individuals, (but the condition is still rare in this patient group). Both anal and cervical cancer have been linked to infection with certain strains of HPV. PAP smear tests are routinely used to check for the presence of potentially cancerous cell changes in the cervix. But it is not known if such screening for anal cancer means that treatment is more likely to work and that survival rates are increased. It is however well established that localised early-stage anal cancer is more likely to respond to treatment than more advanced anal cancer, and some clinicians and treatment advocates have therefore suggested that gay men should have screens similar to PAP smears to check for abnormal cells in the anus. Studies from the US have suggested that as many as 93% of HIV-positive gay men and 14% of HIV-positive women have abnormal cells in the anus. Investigators in Melbourne and Sydney, Australia, wanted to see how many of their HIV-positive patients had abnormal anal cells and infection with high-risk HPV. The study involved 126 patients aged between 18 and 60 (median age, 45 years), most of whom (124, 98%) were gay men. All had a CD4 cell count above 300 cells/mm3, the median CD4 cell count being 545 cells/mm3. An undetectable viral load was present in two-thirds of patients. A quarter of individuals had previously been diagnosed with AIDS. A history of medical or surgical treatment of the anus was present in 25% of patients, and 18% had had anal warts removed. Anal cytology results were available for 113 patients, and 85 (67%) had cells which were to some extent abnormal. Most patients (106, 84%), had anal infection with a high-risk strain of HPV, and 79 (74%) of these individuals had abnormal anal cells. A total of 16 patients (13%) had high-grade pre-cancerous cells changes (high-grade squamous intraepithelial lesion, HGSIL), all of whom had anal infection with high-risk strains of HPV. Furthermore, 13 patients (10%) had cell changes of undetermined significance with possibly high-grade changes, and 92% of these individuals had high-risk HPV strains present. There was no association between the presence of abnormal anal cells with age, current CD4 cell count, viral load, or previous AIDS-defining illness. But previous anal treatment for warts was associated with the presence of abnormal cells (p = 0.04). Statistical analysis showed that patients with high-risk HPV were much more likely to have any abnormal anal cells (odds ratio [OR], 5.03; 95% CI: 1.45 – 17.39), and high-grade or potentially high-grade cell changes (OR, 4.22; 95% CI: 0.766 – 78.89) compared to patients who did not have high-risk HPV in the anus. Further analysis showed a statistically significant association between high-risk strains of HPV and high-grade precancerous cell changes, or potentially pre-cancerous cell changes, in the anus (p = 0.029). The investigators write, “the presence of abnormal anal cytology was significantly associated with anal infection with high-risk HPV types.” But they add, “it should be noted that high-risk HPV type anal infection was also common in people with no detected cytological abnormalities.” They suggest that screening programmes, similar to those used for cervical cancer prevention, may benefit patients with abnormal anal cell changes. However, “before such programmes are introduced, greater understanding is required of the aetiology [natural history] and role of intervention in this condition.” Patients enrolled in the study were given the opportunity to enroll into a study investigating a potential HPV-16 therapeutic vaccine.


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