According to research presented at the conference, people living with HIV who receive topical trichloroacetic acid are about as likely to experience improvement or resolution of precancerous anal cell changes as those who receive electrocautery. patients, but were less likely to experience pain or other side effects. European AIDS Conference (EACS 2023).Another study published in ID Week 2023found that many gay men living with HIV are not being screened to detect anal cancer at an earlier, more treatable stage.
anal cancer, like cervical cancer, is caused by the human papillomavirus (HPV), one of the most common sexually transmitted infections. HPV causes abnormal cell proliferation, or dysplasia, that can progress to precancerous intraepithelial neoplasia (also called squamous intraepithelial lesions) and eventually invasive cancer. People living with HIV, especially men who have sex with men, have a much higher risk of anal cancer than the general population, even if they have adequate CD4 T cell counts and are receiving effective antiretroviral therapy. Become.
anal cancer screening
Although widespread screening and early treatment have dramatically reduced cervical cancer morbidity and mortality, it is still not widely available to people at risk for anal cancer.
Many experts and advocates had hoped this would change after the ANCHOR study showed that screening and prompt treatment of anal tumors reduced the risk of invasive anal cancer by 57%. In that study, participants were screened using anal cytology (Pap test) and high-resolution anoscopy (examination of the anal canal using a magnifying glass). Patients with high-grade squamous intraepithelial disease were randomly assigned to receive immediate treatment or active monitoring.
“We believe that anal cancer precursor screening and treatment should become the standard of care for people over 35 with HIV,” said ANCHOR principal investigator Joel Palefsky, MD, PhD, of the University of California, San Francisco. He told POZ.
However, while some HIV clinics now routinely perform anal cancer tests, the cost remains inadequate.
As reported in IDWeek, Amit Akula, MD, MPH, PHD, of Yale University School of Medicine, and colleagues evaluated a screening cascade at two academic HIV clinics that have offered anal pap tests annually for more than a decade. did. People with abnormal cellular changes (atypical squamous cells of undetermined significance, or ASCUS) or anal intraepithelial neoplasia (AIN) are referred for high-resolution anoscopy (HRA) and treatment of dysplasia.
Researchers retrospectively examined medical records from 2018 to 2022 of HIV-positive men who had sex with men over the age of 35. They identified 432 people eligible for anal cancer screening. The median age of this group was 57 years, almost all were on antiretroviral therapy, and the median CD4 count was 635. More than half (57%) had an anal pap test before 2018, and 24% had a history of anal dysplasia. .
During the 5-year period, 51% had at least one anal pap or HRA test, while 26% had at least two tests and only 13% had three or more tests. People with a history of anal dysplasia were significantly more likely to be screened, while older people and smokers, risk factors for anal cancer, were less likely to be screened. However, screening rates did not differ by race/ethnicity or insurance type.
Approximately one-third of screened patients had an abnormal Pap test during follow-up, and nearly half of these underwent HRA. Of the 365 anal pap tests performed, 56% were negative (no abnormalities), 18% showed ASCUS, and 9% showed grade 1 AIN, but no grade 2 or 3 neoplasm. There was nothing. However, of the 112 HRA tests performed, only 29% were negative, with 19% showing grade 1 AIN and 54% showing grade 2 or 3 neoplasms. These findings suggest that follow-up anoscopy is necessary to accurately diagnose precancerous lesions.
The researchers noted that the anal pap test is “difficult to perform as a screening test.” [the] Real World. Cytologists found that about half of the tests were “unsatisfactory” (unanalyzable), and despite the high prevalence of grade 2 or 3 AIN by anoscopy, the Pap test found “high-grade” AIN. The detection rate for severe lesions is low.” “Better [anal cancer] “Screening tests and implementation models are urgently needed,” they concluded.
Anal cancer treatment
Turning to treatment, Dr. Stefan Esser of Essen University Hospital presented the results of a randomized trial comparing 85% trichloroacetic acid (TCA) with electrocautery for the treatment of anal intraepithelial neoplasia in people infected with HIV. . TCA is a topical drug used to treat genital and anal warts and dysplasia caused by HPV. Electrocautery uses electricity to burn out abnormal lesions. Most people in the treatment arm of the ANCHOR study were treated with electrocautery.
The TECAIN study enrolled 233 patients diagnosed with AIN by HRA from seven German outpatient clinics for biopsy between November 2015 and March 2020. Most were white gay or bisexual men, with a median age of about 49 years. More than 90% had undetectable HIV viral loads, and the median CD4 count was approximately 640. While current CD4 counts are generally high, people with lowest CD4 counts (lowest ever) have more HPV-related lesions and more advanced lesions. People diagnosed with anal cancer within the past 5 years were excluded.
Pap test results showed that 21% of participants had ASCUS, 29% had low-grade squamous intraepithelial lesions, and 32% had high-grade squamous intraepithelial lesions. . The majority (77%) had high-risk, or carcinogenic, HPV types, 10% had low-risk types, and 7% had no detectable HPV. The highest AIN grade was grade 1 in 37%, grade 2 in 30%, and grade 3 in 33%. Esser pointed to study limitations that most participants had a small number of HPV-related lesions and the lesions were small in size.
Approximately half of the participants were randomly assigned to each type of treatment. They received up to four doses of TCA or electrocautery at four-week intervals. The primary efficacy endpoint was “treatment success,” defined as clinically and histologically confirmed resolution or regression of AIN 4 weeks after the last treatment.
In an intention-to-treat analysis 4 weeks after last treatment, 53% of the TCA group reached this endpoint after an average of 2.8 doses and 62% of the electrocautery group reached this endpoint after an average of 2.3 doses. did. Does not meet prespecified noninferiority criteria. However, 67% of both groups experienced “histological cure” or downgrade of AIN stage. Dr. Esser reported that 24% of TCA recipients and 37% of electrocautery recipients experienced “complete clinical healing” four weeks after the first treatment, and 70% each four weeks after the last treatment. % and rose to 83%.
At 24 weeks after the last treatment, 51% of participants in the TCA group and 49% of participants in the electrocautery group experienced clinical and histologic healing or downgrade of AIN, which is a non-inferiority criterion. was met. At this point, 75% and 70%, respectively, showed complete clinical healing. Eight TCA and seven electrocautery patients received additional intervention, mostly with imiquimod cream, between 4 and 24 weeks.
TCAs required significantly higher therapeutic doses to be successful in the clinic, but had fewer side effects. Adverse events were observed in 27% of TCA recipients and 36% of electrocautery recipients. Overall, the most common side effects were pain or burning during or after treatment administration. Those who received electrocautery were almost twice as likely to report pain compared to those who received TCA (25% vs. 14%). Electrocautery recipients were more likely than TCA recipients to require local or general anesthesia or sedation during the procedure (39% vs. 7%) and were more likely to require intervention to control bleeding. (4% vs. 3%). Nevertheless, Esser said both treatments were generally well-tolerated, side effects were mostly mild and temporary, and there were no serious adverse events with either treatment.
“This is the first prospective randomized study to demonstrate comparable outcomes of TCA and electrocautery in treating AIN in HIV-infected people,” the researchers concluded. “TCAs are well-tolerated, cost-effective, and simple treatment options for AIN in HIV-infected people.”
Esser noted that, unlike electrocautery, TCA does not require complex equipment and can be applied without anesthesia in a regular office by a doctor without special training.
He added that recurrence of anal dysplasia is common, so long-term follow-up is needed to determine the durability of treatment. However, in this study, 7% of those successfully treated with TCAs experienced a relapse during follow-up, whereas 22% of those successfully treated with electrocautery found that TCAs had a “more sustainable effect.” ”.
For more news about anal cancer, click here.
Click here for more reports from IDWeek 2023.
Click here for more reports from EACS 2023.