Journal Scan / Research · October 26, 2022 Risk of Nonkeratinocyte Skin Cancers in People Living With HIV During the Era of Antiretroviral Therapy Journal of Investigative Dermatology

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• This study of 585,706 people living with HIV in the age of antiretroviral therapy (ART) found a total of 2743 nonkeratinocyte skin cancers (0.5% of patients). The most common skin cancer was Kaposi sarcoma (82.0%), followed by melanoma (12.0%) and cutaneous lymphoma (2.6%). There was an elevated risk of diffuse large B-cell lymphoma (DLBCL) and Merkel cell carcinoma (MCC) among those with a prior diagnosis of AIDS.

• Kaposi sarcoma remains the most common nonkeratinocyte skin cancer among patients living with HIV during the era of ART, and patients with prior history of AIDS are at risk of other virus-associated cancers such as MCC and DLBCL.

–  Kelly B. Scarberry, MD

Written by

 

 

Klint Peebles MD

This is a large population-based study of non-keratinocyte skin cancers (NKSC) in people living with HIV infection (PLWH) during the antiretroviral therapy era. It is important to remember that PLWH face the complete spectrum of dermatologic conditions, including cutaneous malignancies. And, while entities such as Kaposi sarcoma and other AIDS-defining conditions may be perceived as most classically associated with HIV infection, PLWH may present with any type of skin cancer. That written, this study found that, for most NKSCs, risk was not elevated for PLWH compared with the general population, suggesting that PLWH may not require routine skin cancer screening in the absence of other meaningful risk factors.

Importantly, comments made in this paper regarding screening are made in the context of the cancers specifically investigated in the study, namely NKSCs. The jury is still out regarding risk of keratinocyte skin cancer in PLWH. Prior studies, including meta-analyses, have suggested that HIV infection may be independently associated with a higher incidence of both keratinocyte carcinoma and melanoma, although these studies come with limitations.1-4 A more recent systematic review included four studies, the majority of which did not show any such associations in patients older than 50 years compared with age-matched, HIV-uninfected persons.5 However, it was found that HIV infection might be associated with higher risks of subsequent squamous cell carcinoma in PLWH who already had a history of keratinocyte carcinoma.

Of course, the USPSTF currently does not recommend routine skin cancer screening, and existing care guidelines for PLWH have also yet to offer specific recommendations on skin cancer screening and risk reduction. That written, it is important that a personalized, patient-centered approach be utilized in the care of PWLH given the intersection of multiple factors germane to skin cancer outcomes, including HIV infection itself, degree of immunosuppression, medications, aging, and behavioral risk factors, just to name a few. Regarding the latter, disproportionately high rates of some skin cancers and indoor tanning have been identified in some populations of gay and bisexual men,6 and, given the higher risk of HIV infection in these populations, these intersections further amplify the need for focused research into these risks and how they can be mitigated in a manner that does not unduly conflate distinct populations and risk factors.

Intuitively, PLWH may be at a higher risk for tumors caused by oncogenic viruses, including Merkel cell carcinoma, associated with the Merkel cell polyomavirus, and diffuse large B-cell lymphoma, associated with the Epstein-Barr virus. Conceptually, this mirrors observations in other organ systems in PLWH, specifically the rising incidence of anal dysplasia and anal cancer (caused by the human papillomavirus). In the case of anal cancer, the ongoing increase in incidence despite antiretroviral therapy may be related to the qualitative impacts of HIV infection on the immune system, immunologic dysregulation, and/or decreased efficiency of oncogenic viral surveillance. Further, antiretroviral therapy has allowed for PLWH to live longer and healthier lives, but this also arguably allows for greater opportunities for oncogenic viral replication and transformation.

Ultimately, we must be aware that neither all people within a group nor all skin cancers are homogeneous. PLWH encompass innumerable characteristics from all walks of life, representing all gender identities, sexual orientations, races/ethnicities, countries of origin, and ages. As such, care must be individualized and patient-centered to understand the unique risk factors of the patient in front of you and to most effectively and humbly meet them where they are. 

References

1. Olsen CM, Knight LL, Green AC. Risk of melanoma in people with HIV/AIDS in the pre-and post-HAART eras: a systematic review and meta-analysis of cohort studies. PloS One. 2014;9(4):e95096. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095096 
2. Zhao H, Shu G, Wang S. The risk of non-melanoma skin cancer in HIV-infected patients: new data and meta-analysis. Int J STD AIDS. 2016;27(7):568-575. https://journals.sagepub.com/doi/10.1177/0956462415586316 
3. Omland SH, Ahlström MG, Gerstoft J, et al. Risk of skin cancer in patients with HIV: A Danish nationwide cohort study. J Am Acad Dermatol. 2018;79(4):689-695. https://www.jaad.org/article/S0190-9622(18)30475-4/fulltext 
4. Venanzi Rullo E, Maimone MG, Fiorica F, et al. Non-Melanoma Skin Cancer in People Living With HIV: From Epidemiology to Clinical Management. Front Oncol. 2021;11:689789. https://www.frontiersin.org/articles/10.3389/fonc.2021.689789/full 
5. Yeung H, Balakrishnan V, Luk KMH, et al. Risk of skin cancers in older persons living with HIV: a systematic review. J Assoc Nurses AIDS Care. 2019;30(1):80-86. https://journals.lww.com/janac/Abstract/2019/02000/Risk of Skin Cancers in Older Persons Living With.10.aspx 
6. Mansh M, Katz KA, Linos E, et al. Association of skin cancer and indoor tanning in sexual minority men and women. JAMA Dermatol. 2015;151(12):1308-1316. https://jamanetwork.com/journals/jamadermatology/fullarticle/2453327 

Abstract

Antiretroviral therapy (ART) may alter susceptibility to nonkeratinocyte skin cancers (NKSCs) by improving immunity in people living with HIV (PLWH). Using linked data from HIV and cancer registries in 12 US states/regions during the ART era (1996-2018), we calculated standardized incidence ratios (SIRs) for 27 NKSCs comparing incidence to the general population. Risk factors for NKSCs were evaluated using Poisson regression. There were 2,743 NKSCs diagnosed in 585,706 PLWH followed for 4,575,794 person-years. Kaposi sarcoma (KS) was the most common cancer (82%) followed by melanoma (12%) and cutaneous lymphoma (2.6%). Incidence was elevated for virus-related NKSCs: KS (SIR 147, 95%CI 141-153), diffuse large B-cell lymphoma (DLBCL, 5.19, 3.13-8.11), and Merkel cell carcinoma (MCC, 3.15, 1.93-4.87); elevated incidence for DLBCL and MCC was observed only among PLWH with a prior AIDS diagnosis. KS risk was highest among men who have sex with men. Incidence was not increased for melanoma, adnexal carcinomas, and sarcomas. Melanoma and MCC arose disproportionately on sun-exposed skin, supporting a role for ultraviolet radiation in their development. In conclusion, risk for most NKSCs was similar to the general population during the ART era, suggesting that PLWH without NKSC risk factors may not require intensive skin surveillance.

Journal of Investigative Dermatology

Risk of nonkeratinocyte skin cancers in people living with HIV during the era of antiretroviral therapy

J Invest Dermatol 2022 Oct 07;[EPub Ahead of Print], YT Luu, Q Luo, MJ Horner, M Shiels, EA Engels, MR Sargen 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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