Seville Cohort of People Living With HIV at Risk for Anal Cancer

Overview

There is increasing awareness of augmenting risk of anal cancer in people living with HIV, especially among men who have sex with men (MSM). High resolution anoscopy (HRA) represents the gold standard to detect pre-cancerous anal high-grade squamous intraepithelial lesions (HSIL), however, the procedure is time-consuming, costly and, most importantly, the learning curve is very flat. This yields a poor implementation of anal screening and, likely, to an excess of otherwise preventable anal cancer. Other screening methods include digital ano-rectal examination, anal-rectal cytology and human papillomavirus (HPV) genotyping, since infection with high-risk HPV genotypes has been identified as the main reason for the development of HSIL. To date, there is no consensus in screening strategies. Furthermore, it remains unclear whether, in whom and to which extend the currently available topic and invasive treatment options for HSIL should be applied, given that the natural history of the development of anal cancer remains poorly understood. The present cohort study aims to provide real-life data on the screening, management and follow-up of HIV-infected MSM is warranted for a better understanding of anal cancer in this setting.

The development of anal precancerous squamous intraepithelial lesions (SIL) and cancer of the anus is mainly caused by infection with high-risk human papillomavirus genotypes (HR-HPV). There is increasing awareness of marked (40 to 130-fold) risk of anal cancer in people living with HIV, especially among men who have sex with men (MSM). With the changing scenario of comorbidities in the HIV-infected population, given the success of modern antiretroviral therapy, anal cancer has emerged as a leading neoplasia across different cohorts in Western countries. In 2014, almost 30000 people were newly diagnosed with HIV in Europe, the majority of cases (77%) being men. This was largely driven by HIV transmission between MSM, which accounted for 42% of all HIV diagnoses. Hence, the incidence of anal cancer is likely to increase in the years to come. The number of experts who support the necessity of implementing wide programs of anal cancer screening in at-risk populations is rapidly growing. Indeed, both the European Guidelines for treatment of HIV-infected adults and the Guidelines of the Spanish AIDS Society (GESIDA) currently recommend the screening of anal cancer in HIV-infected subjects at risk. It is likely that in years to come, a general recommendation to screen for anal cancer in patients with different conditions associated with immunosuppression is established, as experienced in other populations. In this context, since HIV-negative MSM and women with a history of anogenital dysplasia, as well as transplant patients, exhibit excess risk of anal cancer, these populations have been typically screened in center with ongoing anal cancer screening programs. Digital ano-rectal examination (DARE) is mainly accepted as the first screening procedure for anal high-risk SIL (HSIL), followed by anal-rectal cytology. Both represent simple methods, however, cytology shows an alarmingly low negative predictive value and furthermore, in case of an abnormal cytology, the patient is referred to high resolution anoscopy (HRA) for biopsy of acetowhite lugol-negative lesions in the anal epithelium, suggestive of HSIL. HRA performance is similar to cervical colposcopy, but unfortunately, the training process is by far longer, hampering its implementation and availability to highly-specialized centers with large cohorts of people living with HIV under care. Although histological HSIL was identified as precursor of anal cancer, it remains unclear if, which and in whom treatment is indicated, since not all patients progress, a considerable proportion even regresses spontaneously and recurrence rates are high. Treatments currently available include topical imiquimod or 5-fluorouracil, as well as surgical treatment. Due to the lack of data, no consensus of HSIL management has been reached. Taken together what was mentioned above, real-life data on the screening, management and follow-up of HIV-infected MSM is warranted for a better understanding of anal cancer in this setting.