Advancing anal cancer prevention: Screening expansion and the emerging role of host-cell DNA methylation

By Rebecca Millecamps, Fujirebio

Anal cancer incidence remains low in the general population but is significantly elevated in defined at-risk groups, including people living with HIV, men who have sex with men (MSM), immunocompromised individuals, and women with a history of HPV-associated disease. Persistent infection with high-risk human papillomavirus (hrHPV) is recognized as the principal causal factor in the development of anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma (ASCC).¹

Recent years have marked an inflection point in the field, driven by three key developments:

1. Evidence that treatment of high-grade squamous intraepithelial lesions (HSIL) reduces progression to anal cancer.¹
2. Identification of the anal cancer incidence by risk group and proposal of a unified anal cancer risk scale.²
3. Publication of updated international screening recommendations supporting structured screening of at-risk populations.³

The objective of screening moves from early diagnosis of cancer towards prevention of cancer through diagnosis and treatment of precancerous lesions in groups at risk. Attention is increasingly turning toward risk stratification tools that may help refine management decisions beyond hrHPV detection and cytology alone.^4,5

From detection to prevention: a changing clinical landscape

The ANCHOR trial demonstrated that treatment of anal HSIL significantly reduced the incidence of progression to invasive anal cancer.¹ These findings have provided an important evidence base for expanded screening recommendations in high-risk populations.³

Previous Fujirebio “Insight” articles have reviewed both the evolving screening guidelines³ and the clinical validation of host-cell methylation testing in anal disease.⁶

Expanded screening, however, introduces complexity. Cytology and hrHPV testing identify cellular abnormalities and high risk HPV infection but do not directly measure the biological transformation processes associated with carcinogenic progression. Many lesions regress or remain stable, while only a subset progress. The ability to distinguish between these trajectories remains a key unmet clinical need.