HPV Biomarkers Predict Risk for Anal Precancer in MSM and Who Have HIV

Anal cancer
Anal cancer
Among men who have HIV who also have sex with men, HPV-related biomarkers provide long-term risk stratification for anal precancers.

Among men who have HIV who also have sex with men (MSM), human papillomavirus (HPV)-related biomarkers provide long-term risk stratification for anal precancers, according to results published in Clinical Infectious Diseases.

The results showed that testing negative on high-risk HPV and dual stain indicated a low risk for high-grade squamous intraepithelial lesion (HSIL) and anal intraepithelial neoplasia grade 2 or more severe diagnoses (HSIL/AIN2+).

The study included MSM who also had been diagnosed with HIV between 2009 and 2010, with passive follow-up through 2015 (n=363). Participants had anal cytology and high-resolution anoscopy at baseline. The researchers calculated the baseline sensitivity and specificity for each biomarker for a combined end point of HSIL/AIN2+. They also estimated the 2- and 5-year cumulative risks for HSIL/AIN2+ using logistic and Cox regression models.

During the study, 129 men were diagnosed with HSIL/AIN2+.

The researchers found that high-risk HPV testing had the highest positivity (36.6%, 95% CI, 32.9%-54.8%) and sensitivity (100%) of all assays, but it also had the lowest specificity (29.4%). They also found that HPV16/18 genotyping and HPV E6/E7 mRNA both had high specificity but low sensitivity.

The results indicated that 2- and 5-year risks for HSIL/AIN2+ were highest for those who tested positive for HPV16/18 or HPV E6/E7 mRNA followed by those who tested positive on dual stain. Those who tested negative on high-risk-HPV or dual stain had the lowest 2- and 5-year risks for HSIL/AIN2+.

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“Screening with p16/Ki-67 dual stain may provide greater reassurance against anal precancer compared to cytology, or at a higher threshold of positivity, may reduce the number of [MSM who also have HIV] who need further evaluation,” the researchers wrote.


Clarke MA, Cheung LC, Lorey T, et al. Five-year prospective evaluation of cytology, HPV testing, and biomarkers for detection of anal precancer in HIV+ MSM [published online November 12, 2018]. Clin Infect Dis. doi:10.1093/cid/ciy970