Treatment of precancerous anal lesions in HIV patients: should they be treated or monitored? : IJS Global Health

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Treatment of precancerous anal lesions in HIV patients: should they be treated or monitored?

Picón-Jaimes, Yelson A. MD, MSca; Rodríguez-Cabarca, Yarath Z. MDb; Pérez-Bertel, Roy R. MDc; Bueno-Prato, Nancy K.J. MDd; Narvaez-Rojas, Alexis R. MDe,

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International Journal of Surgery: Global Health 6(1):p e100, January 2023. | DOI: 10.1097/GH9.0000000000000100
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Controlling the burden of disease of human immunodeficiency virus (HIV) infection is currently one of the top priorities in global health1. According to data from the World Health Organization (WHO), in 2021, 650,000 people died from this infection and 1.5 million acquired it, estimating a total of 38.4 million people in the world with active disease1. One of the complications that can occur in the HIV patient, and which is precipitated by immunosuppression is cancer. In men who have sex with men, high-grade squamous intraepithelial anal lesions (HSIL) are a manifestation that may suggest a malignant process and should raise alarms about the development of anal cancer1–3. Over the years, there has been a discussion on how to treat HSIL in HIV patients, since the time of evolution to cancer is long, and under strict antiretroviral therapy and other measures, it may not even evolve3,4.

In 2014, Berry et al3 followed for 15 years 138 men with HIV and HSIL, who were consistently screened by digital anorectal examination, high-resolution anoscopy, and biopsy. During that period, only 22 (15.9%) men developed anal cancer. In 2017, Deshmukh et al4 analyzed the cost-effectiveness and clinical effectiveness of different management strategies for HSIL in men with HIV, based on data from the SEER database (Surveillance, Epidemiology, and End Results-Medicare). It was found that active surveillance was the most effective strategy in men aged 29 years and below. Also, they found that doing nothing was cost-effective up to 38 years and that treatment of HSIL plus quadrivalent human papillomavirus vaccination was cost-effective for those over 38 years of age. The authors concluded that the most rational approach was to treat only those aged 38 years and above and suggested active surveillance in young patients4.

Now, more recent studies that have further evaluated this phenomenon and compared the natural history of HSIL and anal cancer in men with and without HIV have found that age below 45 years [hazard ratio (HR): 1.64; 95% CI: 1.11–2.41], previous diagnosis of the intraepithelial lesion (P<0.001), infection with human papillomavirus 16 (HR: 3.39; 95% CI: 2.38–4.84) and HIV (HR: 1.43; 95% CI: 0.99–2.06), are significantly associated with the occurrence of HSIL. Particularly, it has been observed that ~22% of these lesions disappear per year and that age below 45 years (HR: 1.52; 95% CI: 1.08–2.16), small lesions (HR: 1.62; 95% CI: 1.11–2. 36), nonpersistent infection with human papillomavirus 16 (HR: 1.72; 95% CI: 1.23–2.41) and anal intraepithelial neoplasia grade 2 (HR: 1.79; 95% CI: 1.29–2.49), are predictors of this involution5. Thus, there is discrepancy and heterogeneity among certain predictors, and this makes it difficult to extrapolate measures of effect and recommendations in guidelines and algorithms, as not all populations behave in the same way or have the same risk.

However, a recent trial by Palefsky et al6 compared monitoring versus treatment of HSIL in 4459 men with HIV, showing that at a median follow-up of 25.8 months, there were 9 cases of cancer in the intervention group (equivalent to 173 cases per 100,000 person-years) versus 21 cases in the control group (equivalent to 402 cases per 100,000 person-years). This resulted in a 57% lower progression rate in the intervention group compared with the monitoring group (P <0.003)6. Thus, a significant benefit was evidenced in the treatment. Gaisa et al7, evaluated the effectiveness of electrocautery ablation of HSIL in 330 people with HIV, who had an average age of 45 years and 49% had multiple HSIL. During a median follow-up of 12.2 months postablation, ~60% of the patients had a global recurrence. It was found that smoking, HIV viraemia, and the rate of multiple lesions were associated with local recurrence, in addition to the prevalence of human papillomavirus types 16 and 187. Thus, it was concluded that although it is an effective option, it is necessary to consider the numerous predictors of recurrence to choose the most cost-effective option.

Vergara-Fernandez et al8 studied radiofrequency ablation in the same population group (n=12), which were young adults (mean age 38 y). At 1-year postintervention, high-resolution anoscopy showed normality in 58.3% of patients, 3 showed recurrence, and 2 showed persistence, which were treated with electrocautery. It is necessary to highlight that individuals reported severe pain with radiofrequency ablation. Thus, radiofrequency ablation was shown to be ~60% effective in immunocompromised patients with HSIL8. Then, the genotypical and clinicopathologic characteristics of anorectal lesions in HIV patients must be known with precision in order to define the most appropriate, cost-effective, and cost-useful behavior9,10.

The above leads to the following conclusions: (1) it is necessary to carry out massive epidemiological, molecular, and genetic studies in male patients with HIV, HSIL, and who have sex with men, in order to evaluate if the behavior described in the literature is similar to that of each sociodemographic, cultural and health context; (2) ~1 in 5 patients with HSIL who have had nothing or only monitoring performed will resolve the lesion; therefore, it is suggested that the lesion be treated to prevent progression to anal cancer; (3) radiofrequency ablation does not have sufficient evidence for its use and, on the contrary, electrocautery proves to be cost-effective and clinically effective; (4) predictors reported in clinical studies should be taken into account to define the most appropriate behavior, according to the availability of therapeutic tools and patient needs. This reaffirms that it is imperative to promote translational, clinical and outcome research in cancer11, as well as to promote research activity in the different stages of medical training12–14, in order to have active researchers in all settings where HIV patients are cared for.

Ethical approval

None.

Sources of funding

None.

Authors’ contribution

All authors equally contributed to the analysis and writing of the manuscript.

Conflict of interest disclosures

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Research registration unique identifying number (UIN)

None.

Guarantor

Alexis Rafael Narvaez-Rojas.

Data statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Provenance and peer review

Commentary, internally reviewed.

References

1. World Health Organization. HIV. 2022. Accessed November 20, 2022 https://www.who.int/news-room/fact-sheets/detail/hiv-aids
2. Centers for Disease Control and Prevention. HIV Statistics Center. 2022. Accessed November 20, 2022 https://www.cdc.gov/hiv/statistics/index.html
3. Berry JM, Jay N, Cranston RD, et al. Progression of anal high-grade squamous intraepithelial lesions to invasive anal cancer among HIV-infected men who have sex with men. Int J Cancer 2014;134:1147–55.
4. Deshmukh AA, Chiao EY, Cantor SB, et al. Management of precancerous anal intraepithelial lesions in human immunodeficiency virus-positive men who have sex with men: clinical effectiveness and cost-effectiveness. Cancer 2017;123:4709–19.
5. Poynten IM, Jin F, Roberts JM, et al. The natural history of anal high-grade squamous intraepithelial lesions in gay and bisexual men. Clin Infect Dis 2021;72:853–61.
6. Palefsky JM, Lee JY, Jay N, et al. Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer. N Engl J Med 2022;386:2273.
7. Gaisa MM, Liu Y, Deshmukh AA, et al. Electrocautery ablation of anal high-grade squamous intraepithelial lesions: effectiveness and key factors associated with outcomes. Cancer 2020;126:1470–9.
8. Vergara-Fernandez O, Solórzano-Vicuña D, Coss-Adame E, et al. Outcomes of radiofrequency ablation for anal high-grade squamous intraepithelial lesions. Tech Coloproctol 2021;25:701–7.
9. Liu Y, Sigel KM, Westra W, et al. HIV-infected patients with anal cancer precursors: clinicopathological characteristics and human papillomavirus subtype distribution. Dis Colon Rectum 2020;63:890–6.
10. Barroso LF, Stier EA, Hillman R, et al. Anal cancer screening and prevention: summary of evidence reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Guidelines. Clin Infect Dis 2022;74(S-2):S179–92.
11. Reyes-Monasterio A, Lozada-Martinez ID, Cabrera-Vargas LF, et al. Breast cancer care in Latin America: the ghost burden of a pandemic outbreak. Int J Surg 2022;104:106784.
12. Mass-Hernández LM, Acevedo-Aguilar LM, Lozada-Martínez ID, et al. Undergraduate research in medicine: a summary of the evidence on problems, solutions and outcomes. Ann Med Surg (Lond) 2022;74:103280.
13. Lozada-Martinez ID, Suarez-Causado A, Solana-Tinoco JB. Ethnicity, genetic variants, risk factors and cholelithiasis: The need for eco-epidemiological studies and genomic analysis in Latin American surgery. Int J Surg 2022;99:106589.
14. Pérez-Fontalvo NM, De Arco-Aragón MA, Jimenez-García JDC, et al. Molecular and computational research in low- and middle-income countries: development is close at hand. J Taibah Univ Med Sci 2021;16:948–9.
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