Mathematical model helps predict anal cancer risk in individuals with HIV infection

Both cervical cancer and anal cancer are caused by the human papilloma virus. Both diseases also share a common precursor: abnormal cells known as high-grade squamous intraepithelial lesions (HSIL).

In cervical neoplasia, treating HSILs has been shown to reduce progression to cervical cancer. Recently published research suggests the same is true for anal cancer: HSIL treatment reduced the risk of progression to invasive anal cancer by 57 percent.

Individuals living with the human immunodeficiency virus or HIV are most at risk for invasive anal cancer, but state and national guidelines regarding the efficacy of cancer screening, which may include physical examination and cell sampling, are mixed and controversial.

In a new study, published June 20, 2022 in the journal Clinical infectious diseasesResearchers from the University of California San Diego School of Medicine and UC San Diego Health describe a new mathematical model to predict anal cancer risk in individuals with HIV infection and to help clinicians and patients make screening decisions.

“Unfortunately, many misconceptions, discomfort, and stigma remain in tackling this topic,” said first author Edward Cachay, MD, a professor of medicine at the UC San Diego School of Medicine and an infectious disease specialist at UC San Diego Health’s Owen Clinic. , the largest primary care center in San Diego for people living with HIV.

“Our goal was to develop a model-based nomogram that would help patients and their physicians make anal cancer screening decisions based on predicted risk profiles.”

Nomograms are mathematical models that calculate relationships between numerical variables. They are often used in cancer forecasting to predict the probability of an event, such as a positive biopsy, risk of recurrence, or survival rate.

In the new study, Cachay and colleagues examined data from 8,139 individuals with HIV who were treated at the Owen Clinic between 2007 and 2020. Of that total, just under half underwent at least one anal cytology test: 65 percent had abnormal anal cytology results, 12.2 percent had HSILs. The adjusted probability of having an HSIL ranged from 5 to 18 percent, depending on patient characteristics and behavioral exposure.

The highest risk observed was associated with men who have sex with men (14 percent) and those who had a CD4 count of less than 200. (CD4 cells, also called T cells, are white blood cells that fight infection and play an important role in the immune system.)

However, the authors noted that no patient characteristic was associated with a predicted HSIL risk of less than 8 percent, highlighting the increased risk of anal cancer among individuals with HIV.

Anal cytology is a simple, inexpensive and uncomplicated component of anal cancer precursor screening. In combination with digital rectal exams, both precursor lesions and established cancers can be identified early in people at risk, Cachay said.

“We have solid evidence from a large randomized controlled trial that treatment of anal HSIL significantly reduces the risk of progression to invasive cancer. Although national consensus guidelines have not yet approved anal cancer screening, we believe there is sufficient evidence to justify shared decision-making discussions between HIV-infected patients and their clinicians about whether or not to screen.

“Our nomogram informs one strand of a screening discussion: the risk of the direct precursor to invasive cancer, HSIL. It estimates quantitative risk based on modeled patient characteristics. Our paper also highlights the limits of risk uncertainty and discusses other important issues that should be included in discussions of shared decision-making regarding screening.”

Co-authors include: Tari Gilbert, Robert Deiss, and William Christopher Mathews, all from UC San Diego.