Automated evaluation of p16/Ki-67 dual stain (DS) cytology was highly sensitive for the detection of anal precancer among men who have sex with men (MSM) with HIV infection, according to results of a study published in Clinical Infectious Diseases.
Biomarkers related to human papillomavirus (HPV) have shown clinical promise for anal cancer screening.
A cross-sectional analysis of 320 patients undergoing anal cancer screening and high-resolution anoscopy (HRA) was conducted between 2009 and 2010. The performance of automated DS cytology was compared with manual DS cytology for the detection of anal intraepithelial neoplasia (AIN) grades 2 and 3 (AIN2+), and AIN3.
Using a combination of cytologic and histologic endpoints, the researchers found that 232 (72.5%) and 88 (27.5%) patients had less than AIN2 and AIN2+, respectively. Of patients with AIN2+, 50 (56.8%) had AIN3. In addition, 83.4% of patients were white, 70.9% were non-Hispanic, the mean age was 52.8 years, and 80.9% were at increased risk for HPV infection, of whom 45.9% were positive for HPV genotypes 16 and/or 18.
The researchers found that the specificity of automated DS cytology for the detection of AIN2+ was statistically significantly increased (50.9% vs 42.2%) and had similar sensitivity vs detection via manual DS cytology (93.2% vs 92.1%). Testing for HPV using automated DS triage was also statistically significantly increased in regard to specificity (56.5% vs 50.9%, respectively) compared with automated DS cytology alone, and sensitivity was the same between both testing methods (93.2%).
Compared with manual DS cytology, automated DS cytology had similar sensitivity (93.2% vs 92.1%) and significantly increased specificity for the detection of AIN2+ (42.2% vs 50.9%; P =.0004). The positive predictive value (PPV) was also statistically significantly increased for automated vs manual DS cytology (41.8% vs 37.7%), with similar results observed for negative predictive value. In regard to AIN3 detection, both sensitivity (45.2% vs 37.8%) and PPV (24.5% vs 21.9%) were statistically significantly increased with automated vs manual DS cytology, with similar results observed for sensitivity (96.0% vs 94.0%).
A modeled analysis that assumed an AIN2+ prevalence of 20% found that automated DS cytology detected an increased number anal precancers compared with both manual DS and anal cytology (186, 184, and 162, respectively). In addition, the rate of referral for HRA due to detection of AIN2+ was most decreased for automated DS cytology, followed by manual and anal cytology (3.1%, 3.5%, and 3.3%, respectively).
This study was limited as the results may not be generalizable to other patient populations, including MSM without HIV infection and women with HIV infection.
According to the researchers, “… automated [DS cytology] shows great clinical utility for optimizing sensitivity and specificity, either alone or in combination with primary HPV screening.” They concluded that “future research should evaluate the performance of automated DS [cytology] for long-term risk stratification in prospective studies, as well as in other populations at [increased] risk for anal cancer.”.”
Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Cohen CM, Wentzensen N, Lahrmann B, et al. Automated evaluation of p16/Ki-67 dual stain cytology as a biomarker for detection of anal precancer in MSM living with HIV. Clin Infect Dis. Published online March 24, 2022. doi:10.1093/cid/ciac211