CROI 2022: ANCHOR study reduces anal cancer by 57% and supports screening for people living with HIV

Kirk Taylor and Simon Collins, HIV i-Base

Anal cancer is an AIDS defining cancer and the fourth most common cancer in people living with HIV in the US. Incidence rates of 160/100,000 person-years are significantly higher than the general population and are highest in gay men older than 45. [1]

HIV also increases the risk for other groups, including heterosexual men and women, also linked to duration for being HIV positive.

Although successfully treatable, especially if diagnosed early, late diagnosis is largely due to a lack of screening programmes, even though the causative link to HPV is the same as for cervical cancer.

The phase 3 ANCHOR study was launched in 2014 to see whether treating HIV positive people with anal high grade squamous intraepithelial lesions (HSIL) could reduce incidence of anal cancer. Secondary outcomes included the efficacy and safety of treatment, including quality of life. [2, 3]

In October 2021, the Data Safety Monitoring Board recommended stopping further randomisation and for all participants to be offered active treatment. [4]

The first trial results from the ANCHOR study were presented by lead investigator Dr Joel Palefsky at a special session of CROI 2022, that also included a wider panel discussion. [5].

Participants were recruited from 15 US sites and randomised to either receive immediate treatment for HSIL or six-monthly active monitoring (AM) with annual biopsy. Both arms could have more frequent monitoring and biopsy if cancer was suspected. Over 10,700 HIV positive people were screened with high resolution anoscopy, with over half (52%) having biopsy-proven HSIL. Rates were similarly high in all groups (53% in men, 45% in women and 62% in trans people).

Nearly all those screened (99.7%) were randomised, stratified by nadir CD4 count (above/below 200 cells/mm³), lesion size, and study site, to either treatment (n=2,227) or AM (n=2,219).

The 17 individuals who were diagnosed with anal cancer at screening (0.16%, 160/100,000) were all referred for immediate treatment, outside the study. This is about 20-fold higher than current rates of cervical cancer in the largely screened US general population.

Baseline demographics included median age 51 (IQR: 44 to 57) and people had been living with HIV for a median of 17 years (IQR: 10 to 25). Approximately 80% were male, 16% female and 3% transgender. Ethnicity included 42% African-American, 23% white, 16%  Hispanic.

Approximately 32% were current smokers, with CDC likely risk group including 78% gay men, 23% heterosexual, 7% drug users and 3% blood products or other.

HIV characteristics included mainly controlled viral load was (80% <50, 7% 50 to 200 and ~5% >1000 copies/mL), median CD4 count approximately 600 cells/mm³ (IQR: 400 to 850) and roughly half had a nadir CD4 <200. Participants had been diagnosed with HIV for a median 17 years (IQR: 10 to 24).

Participant characteristics were similar between groups.

Treatment was primarily by office-based electrocautery (93%), with smaller numbers using infrared or topical treatments.

DSMB were informed when 32 cancers were diagnosed, of which 30 were included in the final analysis. Invasive cancers were more common in the AM arm (21 vs 9). Median follow-up time was 25.8 months and a 57% reduction in anal cancer was observed (95% CI: 6% to 80%; p=0.029). The annual incidence rate of anal cancer was 173 vs 402/100,000 in the treatment vs monitoring arm respectively.

The randomised arm of the study was stopped early and treatment recommended for all participants, with follow-up continuing for another two years.

Overall, there were 54 vs 48 deaths in the treatment vs AM arms, none related to the study; similar adverse events (683 vs 635) and serious events (586 vs 658).

There were seven study-related serious adverse events were in the treatment arm, of which five related to the treatment procedure and two were infection or abscess due to anal biopsy. There was a single biopsy related serious adverse event in the AM arm.

The authors concluded that this is the first study to prove that treatment of anal HSIL is effective in preventing anal cancer and that these data should be used to support screening and treatment as a new standard of care.

They also commented that training programmes are required to improve detection of anal cancers and support roll-out of screening programmes for high-risk individuals, and also to further improve treatment.

It also sets a significant challenge for how these results can be immediately used, given the high prevalance of HSIL and the current lack of resources to screen and treat (see comments below).

comments

The ANCHOR study is a significant achievement for producing a dataset that should support new services and a new standard of care for people living with HIV.

It is also significant for engaging so many people diagnosed with HSIL to agree to monitoring in the control arm. Although immediate treatment of HSIL seems intuitive, it does carry uncertain risks due to greater size of anal lesions (compared to cervical screening) and that lesions can be missed, badly treated or can recur.

The ANCHOR study is also working to identify biomarkers that will predict risk of progression.

However, the very high prevalence of HSIL means that screening algorithms should prioritise HIV positive people with symptoms. Following digital exam, HRA should then be prioritised for those with bumps. Older men with longer duration of infection and lowest CD4 nadir are also factors for higher risk.

Several HIV clinics in the UK already offer screening services or are running research studies. 

The Royal Free Hospital has an ‘opt in’ referral pathway straight to an HRA clinic and plan to start a programme where based on people checking themselves monthly, similar to self-breast exams. They can then report lumps or changes early.

The Chelsea and Westminster Hospital have services at 10 Hammersmith Broadway, the Kobler Centre and 56 Dean Street that includes anal smears tests and anoscopy to those with higher grade abnormalities.

Although this list is London-centric, other services are likely to be available nationally. Please contact i-Base with details to expand this online list.

A recent natural history study of HSIL in gay and bisexual men (about one-third were HIV positive) reported that about 20% cases of HSIL reversed without treatment. [6]

NB:Full results have since been published in the NEJM. [7]

References

Unless stated otherwise, references are to the 29th Conference on Retroviruses and Opportunistic Infections, 12–16 and 22–24 February 2022, virtual meeting. Depending on CROI policy, links might require conference registration and might only be active for a limited time on this platform after the meeting.

1. Clifford GM et al. A meta-analysis of anal cancer incidence by risk group: Toward a unified anal cancer risk scale. Int J Cancer. 2021 Jan 1;148(1):38-47. doi: 10.1002/ijc.33185. Epub 2020 Jul 29.
   https://pubmed.ncbi.nlm.nih.gov/32621759
2. ANCHOR Study website.
   https://anchorstudy.org
3. ClinicalTrials.gov. Topical or ablative treatment in preventing anal cancer in patients with HIV and anal high-grade squamous intraepithelial lesions (ANCHOR).
   https://clinicaltrials.gov/ct2/show/NCT02135419
4. Early treatment prevents anal cancer in people living with HIV: ANCHOR study stops early. (HTB 12 March 2020).
   https://i-base.info/htb/41378
5. Palefsky J et al. Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer. CROI 2022. 12-16 February 2022, virtual. Special Session Oral presentation 106.
   https://www.croiconference.org/abstract/treatment-of-anal-high-grade-squamous-intraepithelial-lesions-to-prevent-anal-cancer/
6. Poynten M et al. The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men. Clinical Infectious Diseases, 72(5);853–861. DOI: 10.1093/cid/ciaa166. (1 March 2021).
   https://academic.oup.com/cid/article/72/5/853/5826154
7. Palefsky J et al. Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer. N Engl J Med 2022; 386:2273-2282
   DOI: 10.1056/NEJMoa2201048. (16 June 2022).
   https://www.nejm.org/doi/full/10.1056/NEJMoa2201048

This report was first posted on 15 February 2022.