Screening for precancerous lesions can prevent rectal cancer

/ Sebastian Kaulitzki, stockadobecom

San Francisco – Screening and early treatment of high-grade anal intraepithelial lesions (HSIL), a precursor to HPV-induced cancer, have reduced the incidence of rectal cancer by almost half in a randomized phase 3 study in HIV-infected people now in New England Journal of Medicine (NEJM 2022; DOI: 10.1056 / NEJMoa2201048) show published results.

Like cervical cancer, anal cancers are caused by oncogenic variants of human papillomavirus (HPV). In both cases, these are initially intraepithelial lesions, which gradually develop into cancer.

For decades, there has been effective early detection of cervical cancer, which has led to a significant reduction in the incidence of cancer. For anal cancer, such screening would hardly be worthwhile because cancer is very rare.

The exceptions are HIV-infected people, who can become infected during anal sex. In HIV-infected men who have sex with men (MSM), the incidence of anal cancer in the United States is estimated at 89 / 100,000 persons-years, in HIV-infected women, the incidence was estimated at 18.6 and 35.6 / 100,000 persons-years. years.

In both groups, HPV-induced cancer is more common in the United States (and probably in Europe) than cervical cancer in women (7.5 / 100,000 person-years). Regular screening of this risk group could therefore be useful.

As with gynecological cancer screening, screening would specifically look for cancer precursors. As with cervical cancer, a “low grade squamous intraepithelial lesion” (LSIL) – formerly known as CIN1 in cervical screening – initially occurs, which can develop into a “high grade squamous intraepithelial lesion” (HSIL), which gynecologists also call CIN2 / 3 and which is the reason for treatment.

The US National Cancer Institute has been researching in recent years whether early removal of HSIL can prevent the development of rectal cancer. The phase 3 study included 10,723 people living with HIV aged 35 and over at 25 centers in the United States. HSIL was found in 4,459 participants during high-resolution anoscopy.

These were then randomized to immediate treatment or active observation. The treatment for most patients consisted of outpatient electrocautery, in which heat was used to destroy the lesions. Both groups underwent follow-up anoscopy every 6 months to detect and eliminate cancer in a timely manner.

During a median follow-up of 25.8 weeks, 9 subjects (173 per 100,000 person-years) were diagnosed with rectal cancer in the HSIL immediate removal group compared to 21 people (402 per 100,000 persons) in the active observation group.

Joel Palefsky of the University of California, San Francisco and his colleagues found a 57% lower rate of progression, which was significant with a 95% confidence interval of 6 to 80%.

According to Palefsky, the results clearly support the screening and early removal of HSIL, which was associated with only minor side effects in the study: only 7 of 2,227 patients had serious treatment-related complications such as abscesses (3 patients), pain (3 patients) or skin ulceration (1 patient) after topical application of fluorouracil, an alternative treatment to cauterization. © rme /

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