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Anal cytology tests useful for detecting pre-cancerous cell changes in patients with HIV

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Anal cytology tests useful for detecting pre-cancerous cell changes in patients with HIV

Michael Carter, Monday, January 18, 2010

Anal cytology may be a useful tool for detecting pre-cancerous cell changes that can lead to anal cancer, UK investigators report in the online edition of AIDS. 


However, the performance of the test depended on the amount of disease present. In addition, it was more accurate in patients with CD4 cell counts below 400 cells/mm3 than in patients with stronger immune systems. 


The investigators believe that their finding that the screening tool is especially accurate in patients with lower CD4 cell counts is important, “given the late diagnosis of HIV in a proportion of people with HIV and further increased risk of anal cancer in this group”. They also note that the accuracy of anal cytology is comparable to cervical cytology. 


Rates of cervical cancer in England fell dramatically after screening programmes were introduced. By contrast, the number of cases of anal cancer diagnosed in recent years has increased. Especially high rates of the disease are seen in HIV-positive individuals. 


Before anal cancer develops, the pre-cancerous lesions form in the anus. These are called anal intraepithelial neoplasia. Prompt diagnosis means that these pre-cancerous changes can be effectively treated. 


Despite having high rates of anal cancer, HIV-positive patients are not routinely screened for pre-cancerous cell changes. This is partly because there is limited and contradictory information about the accuracy of screening methods, one of which is cytology. 


Screening methods such as biopsies, used to produce histological readings, or high-resolution anoscopy can be uncomfortable. 


Investigators in London started using anal cytology (or pap) tests in 2005 and wished to gain a better understanding of their accuracy. 


They therefore compared performance of anal cytology against anal histology and high-resolution anoscopy. The cytology test was easy to perform and involved inserting a swab 5cm into the anal canal. 


The study involved 395 individuals who were screened between 2005 and 2009. Most (93%) were men and 54% were HIV-positive. These patients provided 584 smear results for evaluation. 


“This is a real-life, clinical practice-based study”, comment the investigators. 


The investigators conducted sensitivity analyses. This determined how many cases of pre-cancerous anal cell changes the cytology test detected that had been diagnosed using either histology or high-resolution anoscopy. 


Overall, cytology detected 70% of the cases diagnosed using histology and 69% of those diagnosed with high-resolution anoscopy. 


Cytology detected 71% of the cases of pre-cancerous disease in gay men that were diagnosed using histology. The figure for heterosexuals was 58%. Similar results were seen when cytology was compared to high-resolution anoscopy. 


In both new and follow-up patients, anal cytology was more accurate when two or more areas of disease were present. 


Anal cytology was more accurate in HIV-positive than HIV-negative individuals. This was the case when the results were compared to those obtained from high-resolution anoscopy (sensitivity 75% vs 61%, p = 0.015) and histology (76% vs 59%, p = 0.009). 


High grade disease was detected by anal cytology in 80% of cases in HIV-positive patients and in 93% of cases when the patient was HIV-negative. 


Amongst patients with HIV, the anal cytology test was more accurate amongst patients with a CD4 cell count below 400 cells/mm3. In these patients, it detected 90% of the cases of disease compared to a sensitivity of 80% at higher CD4 cell counts. 


The investigators therefore believe that anal cytology may be an especially useful screening tool in patients who have their HIV diagnosed late. 


In patients taking antiretroviral therapy, cytology detected 77% of the cases of disease identified by histology. Cytology had similar efficacy in patients not taking HIV treatment, having a sensitivity of 73%. Identical results were seen when the cytology results by HIV treatment status were compared to high-resolution anoscopy outcomes. 


Statistical analysis showed that anal cytology was significantly more accurate in patients with more extensive anal disease (p < 0.0001) and in HIV-positive patients with lower CD4 cell counts (p = 0.048). 


Finally, the investigators found that cytology was more accurate in patients with new diagnoses. The test detected 74% of the cases of disease in new patients that were diagnosed using high-resolution anoscopy, and 63% of those using this screening method in follow-up patients. 


“Given the inaccuracies that exist with any method of evaluation, we need to have a number of assessment methods for the diagnosis of anal neoplasia, as is the case with cervical neoplasia”, write the investigators. 


“This study supports the introduction of earlier screening in HIV-positive patients, given their higher burden of anal disease and increased sensitivity with lower CD4 cell count levels”, conclude the investigators. 


Reference 

Mayura N et al. Performance of anal cytology in a clinical setting when measured against histology and high-resolution anoscopy findings. AIDS 24 (online edition), 2010.

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