An international study led by the Infectious Diseases Service of the Ramón y Cajal University Hospital and the Ramón y Cajal Health Research Institute (IRYCIS) has identified two new markers for the detection of high-grade squamous intraepithelial lesions (HSIL), forerunners of the anal cancerin the anal microbiome of people with HIV. Human papillomavirus can cause preinvasive high-grade squamous intraepithelial lesions (HSILs) as precursors to cancer in the anogenital area, with the microbiome suggested as a contributing factor. Men who have sex with men (MSM) living with human immunodeficiency virus (HIV) are at high risk of anal cancer, but current screening strategies for detection of HSIL lack specificity.
This is the objective that was sought to be improved in this work, published in Nature Medicine, which has had the participation of various groups from the Infectious Diseases area of the CIBER (CIBERINFEC), the La Paz Hospital, the Jiménez Díaz Foundation and the Higher Council for Scientific Research (CSIC); as well as the University of Hohenheim (Stuttgart, Germany), the University of Oslo, the U. of Bangor (UK) and the University of Milan.
The research team studied 213 participants, most of them men who have sex with other menand who are being followed up by anoscopies and anal biopsies for presenting a higher risk of developing anal cancer.
“Overexpressed proteins in the microbiome of patients with high-grade squamous intraepithelial lesions seem to contribute to the pathogenesis of cancer,” highlights manuel ferrer, of the CSIC. The findings of this work highlight that more important than knowing which bacteria are present is understanding what those bacteria are doing. And they suggest that, beyond their value in detecting HSIL, bacteria play an important role in its development. “We should investigate these proteins and molecules as possible therapeutic targets to fight cancer“adds the researcher.
Progress to improve the prevention of anal cancer in patients with HIV
The team employed a variety of techniques to analyze the anal microbiome and defined changes in its composition and metabolic activity (production of proteins and molecules). Although no clear signatures of microbiome composition associated with HSIL have been found, anal bacteria associated with these lesions have been identified as overexpressing proteins involved in the production of the compound succinyl-CoA and cobalamin, a vitamin B complex nutrient required by the body in small amounts to function and stay healthy, with levels consistently elevated in subjects with HSIL.
“Our discovery of two new biomarkers for which screening methods can be easily established could improve the current anal cancer screening strategy.”
The research indicates that the combination of succinyl-CoA and cobalamin It outperforms anal cytology in diagnostic performance, since it improves sensitivity, specificity and predictive values.
“Our discovery of two new biomarkers for which detection methods can be easily established could improve the current anal cancer screening strategy,” he explains. Sergio Serrano-VillarCIBERINFEC researcher at the Ramón y Cajal University Hospital / IRYCIS and project coordinator.
“We believe our findings have the potential to reduce the burden of this devastating disease. But beyond that, our study demonstrates the potential of harnessing the microbiome to discover scalable diagnostic markers,” adds Serrano-Villar.
The next step is to develop a cost-effective, non-invasive diagnostic test that can be used in clinical practice to improve screening and prevention of anal cancer in people with HIV.
Source: UCC+i CIBER Scientific Culture Unit