Full results from ANCHOR study published in NEJM
Simon Collins, HIV i-Base
Results from the large US ANCHOR study showing the importance of actively treating high grade interepithelial lesions (HSIL) to prevent anal cancer have now been published in the NEJM. 
Even though cases of anal cancer are rare, the incidence among HIV positive gay men is 89 per 100,000 person-years. The rate in women living with HIV is from 18.6 to 35.6.
In the general population, this compares to rates of 1.6 for anal cancer and 7.5 for cervical cancer among women in the US.
Screening approximately 10,000 people living with HIV who were older than 35 led to roughly half being diagnosed with HSIL. Of these, ANCHOR randomised 4446 participants to either treatment (mainly with clinic-based electrocautery) or to active monitoring.
Over a median follow-up of 26 months, participants in the active arm were 57% less likely to progress to anal cancer (95%CI: 6 to 80; p=0.03). Overall, 30 participants were diagnosed with invasive anal cancer (9 active, 21 monitoring only).
Benefits were also reported for the small number of people in the active arm (n=25) who were non-adherent to active treatment.
The NEJM paper includes more details about progressions rates. For example, progression rates per 100,000 person-years were 173 (95%CI: 90 to 332) vs 402 (95%CI: 262 to 616) in the active vs monitoring groups respectively. This was higher than expected in the control arm, perhaps due to earlier diagnosis of HSIL. It also shows that treatment was not always successful.
Time to progression (hazard ratio) was also significantly associated with lesion size (HR 5.26; 95% CI: 2.54 to 10.87) but not with nadir CD4 count (HR: 1.93; 95% CI: 0.88 to 4.23).
However, nadir CD4 count was <200 cells/mm3 in 70% (21/30) in the group with progression vs 50% (2230/4416) in those without.
The rate of progression was also significantly higher in participants with a lesion size of more than 50% of the anal canal or perianal region.
The ANCHOR study is remarkable for producing a long-needed data set comparable to the one that enabled cervical screening programmes. It is also a considerable achievement that so many participants agreed to be randomised to a monitoring arm after HSIL had been diagnosed.
Of the 30 people who developed anal cancer,10 had superficial squamous cell cancer which is usually just excised. Probably at most 20 required more aggressive chemoradiotherapy and only one had stage 4 disease which is likely to be incurable.
These results are also only possible because ANCHOR included early screening.
This was one of the headline studies from CROI 2022 that we reported in details in HTB in March. 
Comments to this earlier report include details of UK HIV clinics that currently offer screening for HSIL.
These include Homerton, UCL, the Royal Free and the Chelsea and Westminster hospitals.
Although the results support wider availability of screening and treatment it is unclear how this data will be used in the UK.
ANCHOR hasn’t reported number needed to treat (NNT) to prevent one case of anal cancer, which will be needed to pass the different NICE cost-effectiveness thresholds for screening and treatment.
Public pressure and lobbying might also be important.
- 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 (main article)
https://www.nejm.org/doi/suppl/10.1056/NEJMoa2201048/suppl_file/nejmoa2201048_appendix.pdf (supplementary material)
- ANCHOR study reduces anal cancer by 57% and supports screening for people living with HIV. HTB (1 March 2022).
This report was first published on 16 June 2022.