Screening and early treatment reduce anal cancer risk by 57% in people living with HIV

Professor Joel Palefsky at CROI 2022.
Professor Joel Palefsky at CROI 2022.

Screening for precancerous anal cell changes and treating them early lowers the risk of progression to anal cancer in people living with HIV, according to results from the ANCHOR study presented this week at the Conference on Retroviruses and Opportunistic Infections (CROI 2022).

“This is the first demonstration that screening and treatment reduces the risk of anal cancer,” said ANCHOR lead investigator Professor Joel Palefsky of the University of California at San Francisco. “I think the data support inclusion [of screening and treatment] in the standard of care for people with HIV over 35.”

Anal cancer is uncommon in the population at large, but rates have been rising for both men and women since the 1970s, Palefsky said. Like cervical cancer, anal cancer is caused by human papillomavirus (HPV), one of the most common sexually transmitted infections. The virus triggers abnormal cell changes that can progress to precancerous dysplasia (known as high-grade squamous intraepithelial lesions, or HSIL) and invasive cancer.

Professor Joel Palefsky talks about the anal cancer study at CROI 2022.

The incidence of anal cancer is much higher among people living with HIV, for whom it is the fourth most common cancer. Previous research has shown that people living with HIV have more types of HPV, are less likely to naturally clear the virus and experience more rapid progression to HSIL or cancer. Even people on effective antiretroviral therapy with a high CD4 count can develop anal dysplasia and cancer. Men who have sex with men are especially prone to anal cancer; other groups at risk include older individuals, women with cervical cancer and people with compromised immunity for other reasons.

Widespread screening and early treatment have dramatically lowered the prevalence and mortality of cervical cancer since the 1950s, but these interventions are not the standard of care for HIV-positive people at risk for anal cancer. The reason, Palefsky said, has been lack of evidence that they would work. Many at-risk people have multiple precancerous lesions, clinicians may miss or inadequately treat lesions, and new lesions often arise after treatment, leading to what Palefsky termed “anal whack-a-mole”.

Study design

The ANCHOR – or Anal Cancer HSIL Outcomes Research – trial was designed to address this question. The study aimed to determine whether treating anal HSIL can reduce the incidence of anal cancer in people living with HIV and whether doing so is safe. It also looked at quality of life, and is creating a data and specimen bank to aid further research into factors that contribute to disease progression.

The study enrolled people with HIV aged 35 and older in 15 US cities. At study entry, they were screened for HSIL using anal Pap smears (cytology) and a technique called high-resolution anoscopy, in which a magnifying scope is used to examine the anal canal. If HSIL was suspected, a biopsy sample was collected for analysis.

Participants found to have HSIL were randomly assigned to receive immediate treatment or active monitoring. Those in the monitoring arm returned for repeat screening every six months or more often if deemed to be at higher risk. People found to have anal cancer at any point were referred for further evaluation and treatment.

The most common treatments were electrocautery (hyfrecation) or infrared coagulation, two methods that use electricity or heat to remove abnormal lesions. Other treatments included topical imiquimod or 5-fluorouracil creams, or surgery in the most advanced cases.

Study results

A total of 10,723 people with HIV were screened between September 2014 and August 2021. More than half (53% of men, 46% of women and 63% of transgender people) were found to have HSIL at study entry, and 17 were diagnosed with pre-existing anal cancer. HSIL prevalence was about what was expected for men, but it was higher than expected for women, a group that mostly had not been screened before, Palefsky noted.

Out of this group, 4446 people with HSIL were randomly assigned to the immediate treatment arm (2227 people) or the active monitoring arm (2219 people). The median age of the randomised participants was 51 and they had been living with HIV for a median of 17 years. A large majority (80%) were men – mostly gay or bisexual – 16% were women and about 3% were transgender. About a third were White, 42% were Black and 16% were Latino. More than 80% were on antiretroviral therapy with an undetectable viral load and the median CD4 count was approximately 600.

The trial was halted ahead of schedule in October 2021 after an interim analysis showed that screening and early treatment confers a clear benefit: removing HSIL significantly reduced the risk of progression to anal cancer. A data safety and monitoring board recommended that everyone in the monitoring arm should be offered treatment, and participants will continue to be followed.

Nine people in the immediate treatment arm and 21 people in the active monitoring arm were diagnosed with invasive anal cancer, reflecting a 57% risk reduction in the treatment group. The incidence of anal cancer was 173 cases per 100,000 person-years of follow-up in the immediate treatment group compared with 402 cases in the monitoring group. Among those diagnosed with anal cancer in both study arms, most were at an early stage.

Over the course of the study, 86% of participants received one type of treatment, 10% received two types and about 2% received three or four types. Treatment was generally safe and well tolerated. Seven people in the immediate treatment group and one in the monitoring group experienced serious adverse events related to biopsy or treatment procedures.

Implications for people with HIV

These findings support the inclusion of routine screening and early HSIL treatment as part of the standard of care for people living with HIV, Palefsky told reporters at a CROI media briefing. The results should also encourage health systems and insurers to cover the cost of these procedures.

Although the ANCHOR study was limited to people with HIV, the results will likely be applicable to other groups at increased risk for anal cancer, including HIV-negative men who have sex with men, women with a history of cervical or other HPV-related cancers, and people with immunosuppression for reasons other than HIV.

However, the lack of clinicians trained to perform high-resolution anoscopy remains a barrier. What’s more, there is a need for biomarkers to help predict who is at greatest risk for HSIL progression or, conversely, who is most likely to experience regression without treatment. And there is “room for improvement” in the treatment of anal HSIL, Palefsky said.


squamous intraepithelial lesion (SIL)

This term is used to describe the detection of abnormal cells that have been ‘transformed’ by HPV into a possibly pre-cancerous state. According to the degree of cell change this will be called low-grade or high-grade SIL (LSIL or HSIL). If SIL is detected, a colposcopy will usually be ordered.

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.


Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.


The cervix is the neck of the womb, at the top of the vagina. This tight ‘collar’ of tissue closes off the womb except during childbirth. Cancerous changes are most likely in the transformation zone where the vaginal epithelium (lining) and the lining of the womb meet.

standard of care

Treatment that experts agree is appropriate, accepted, and widely used for a given disease or condition. In a clinical trial, one group may receive the experimental intervention and another group may receive the standard of care.

A digital rectal exam can detect abnormal anal growths, and Palefsky recommended this as a first step for people living with HIV. When the availability of high-resolution anoscopy is limited, he said that first priority should go to people who have symptoms of anal HSIL or cancer, including pain, bleeding and new lumps. The next priority should be older individuals and those with a low current or nadir (lowest-ever) CD4 count.

The prevalence of HPV is high among people with HIV in many countries, even if anal cancer is currently rare. “Anal cancer will increase as the HIV population ages,” Palefsky said. “This is a great time to train the workforce and get them ready for when that inevitable increase happens.”

While these results are good news, prevention of anal cancer would be even better than early detection and treatment. Although smoking – a known risk factor for HPV-related cancers – did not reach the threshold for statistical significance in ANCHOR, Palefsky noted that just over 60% of people who progressed to anal cancer were smokers compared with about 30% of the study population as a whole.

Vaccination can prevent HPV infection in the first place. The Gardasil 9 vaccine protects against nine high-risk HPV types that cause cancer or genital warts. The vaccine is recommended for girls and boys at age 11 or 12 in the US and at age 12 or 13 in the UK, with catch-up vaccination through age 25 or 26 in the general population. HIV specialist societies and guidelines recommend that people living with HIV under the age of 45 who missed vaccination when they were younger discuss it with their doctor.


Palefsky J et al. Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer. Conference on Retroviruses and Opportunistic Infections, abstract 106LB, 2022.

View the abstract on the conference website.

Update: Following the conference presentation, this study was published in a peer-reviewed journal:

Palefsky J et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. The New England Journal of Medicine, 386: 2273-2282, June 2022.

DOI: 10.1056/NEJMoa2201048