Anal HSIL treatment key to anal cancer prevention in PLHIV?

In persons living with HIV (PLHIV) with anal high-grade squamous intraepithelial lesions (HSIL), treatment of the lesions reduced the risk of progression to anal cancer compared with active monitoring, the phase III ANCHOR* trial has shown.

“Anal cancer is among the limited types of cancers that are potentially preventable through treatment of known cancer precursors … The prevention of anal cancer [which is preceded by HSIL] is desirable because anal cancer is associated with poor survival when detected at late stages,” said the researchers.

“Our data show that treatment of anal HSIL, primarily with office-based electrocautery, significantly reduced the risk of progression to anal cancer among PLHIV aged ≥35 years. Such treatment was associated with a low incidence of serious adverse events (AEs),” they continued.

A total of 4,459 PLHIV (median age 51 years, 80 percent male) with biopsy-proven anal HSIL (AIN*3 or p16-positive AIN2) were randomized 1:1 to receive either HSIL treatment or active monitoring without treatment. Participants in the treatment arm were treated until complete resolution of the lesions. [N Engl J Med 2022;386:2273-2282]

Office-based electrocautery ablation (primarily hyfrecation) was the most common HSIL treatment modality used (in 83.6 percent of participants), followed by infrared coagulation (4.8 percent), topical fluorouracil (4.5 percent), ablation or excision under anaesthesia (2.3 percent), and topical imiquimod (0.5 percent).

After a median follow-up of about 26 months, nine cases of invasive anal cancer were diagnosed in the treatment arm, which was markedly less than the 21 reported in the active-monitoring arm. “All cases were confirmed on central pathological review,” the researchers noted.

The observed rate of progression to cancer in the treatment arm was nearly 60-percent lower than those in the active-monitoring arm (173 vs 402/100,000 person-years; p_log-rank=0.03).

At 48 months, the cumulative incidence of progression to anal cancer in the treatment arm was only half of what was reported in the active-monitoring arm (0.9 percent vs 1.8 percent).

Of the eight trial-related serious AEs, seven were from the treatment arm. A total of 103 deaths were reported, of which 55 were from the treatment arm. None of the deaths were deemed related to the interventions.

Strong prevention efforts warranted

The risk of anal cancer is high among PLHIV given their susceptibility to anal HPV infection and anal HSIL. [Int J Cancer 2021;148:38-47; Lancet HIV 2021;8:e531-e543] “The high rate of progression from HSIL to cancer among PLHIV in our trial highlights the need for strong prevention efforts,” the researchers said.

“Treatment of anal HSIL is particularly challenging in PLHIV owing to a large lesion burden and number as reflected by high rates of HSIL recurrence or metachronous disease with currently available methods of treatment,” they continued. “[Hence, there is a] need for more effective HSIL treatment approaches and for close follow-up after HSIL treatment.”

Despite the efficacy of HPV vaccination in preventing initial acquisition of anal HPV38 and development of anal HSIL in young PLHIV, the researchers underlined the need for secondary prevention programmes for those already exposed to anal HPV. [Clin Infect Dis 2021;73:1388-1396]

The investigators also underscored the need for additional research to improve screening algorithms in identifying anal HSIL, given the limitations of high-resolution anoscopy (eg, cost, availability), anal HPV testing, and anal cytologic analysis. [Cancer Cytopathol 2018;126:447-460] “Expansion of diagnostic and therapeutic training programmes in the use of high-resolution anoscopy is also needed,” they added.

“[Taken together,] our data provide support for the use of screening and treatment for anal HSIL as the standard of care for PLHIV aged ≥35 years,” the researchers concluded. “Our data may also be relevant for other groups at increased risk for anal cancer.”