Strategies for screening and early detection of anal cancers: A narrative and systematic review and meta‐analysis of cytology, HPV testing, and other biomarkers

Abstract

Anal cancer incidence and mortality have been increasing over the past decade. Although the incidence in the general population remains low, it is much higher in certain subgroups, including those living with human immunodeficiency virus and men who have sex with men. Approximately 90% of anal squamous cell cancers are caused by infection with carcinogenic human papillomavirus (HPV). Given the common etiology between anal and cervical carcinogenesis, screening for anal cancer has been proposed in certain high-risk populations using strategies adapted from cervical cancer prevention. In this review, the authors discuss important differences in anal and cervical cancer regarding the populations at risk, disease natural history, and clinical procedures and outcomes that need to be considered when evaluating strategies for anal cancer screening. They also performed a systematic review and meta-analysis of the performance of anal cytology, anal HPV testing, and various biomarkers for the detection of anal precancers and cancers. The implications of these performance estimates are summarized in the context of risk-based screening and management of anal precancers, and important research gaps are highlighted that need to be addressed to fully understand the benefits and harms of anal cancer screening. Cancer Cytopathol 2018. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Identification of HPV genotypes causing cervical precancer using tissue‐based genotyping

“…Going forward, it will be important to validate our findings in even larger studies. Biomarkers of transforming HPV infections, such as HPV gene‐specific DNA methylation and E6/E7 oncoprotein expression, may help distinguish the causal hrHPV genotype and may be less costly and laborious compared to LCM …”

“…Biomarkers of transforming HPV infections, such as HPV genespecific DNA methylation and E6/E7 oncoprotein expression, may help distinguish the causal hrHPV genotype and may be less costly and laborious compared to LCM. [19][20][21] Conflict of interest Dr J.T. declares that he is a current employee at Merck, but completed all work associated with this manuscript while employed at the National Cancer Institute.…”

ART is key to clearing oncogenic HPV genotypes (HR-HPV) in anal mucosa of HIV-positive MSM

“…Around one-quarter of the HSIL+ mucosa samples had normal cytology; hence, according to current HSIL/ASCC screening recommendations [36], 11 (6.7%) patients (10 with HSIL and 1 with ASCC) would not have been diagnosed or treated. In contrast, no HSIL + samples were found among those with normal cytology and negative HR-HPV PCR.…”

mRNA Detection in Anal Cytology: A Feasible Approach for Anal Cancer Screening in Men Who Have Sex with Men Living With HIV

“…Although anal cancer is infrequent in the general population, over the past decade its incidence and mortality have increased by about 2.2% and 2.9% per year, respectively [1]. The incidence of anal cancer is mainly concentrated in some specific, well-defined groups of patients, including men who have sex with men, particularly those living with human immunodeficiency virus (HIV), other non-HIV-related immunosuppressed populations, and women with human papillomavirus (HPV)-associated disease [2][3][4][5].…”

“…Indeed, the common etiology of these two cancers (HPV) has prompted the use of the screening strategies performed for cervical cancer to prevent anal cancer. However, there are important differences between these two diseases that need to be addressed in the populations at risk [2][3][4]: the diverse evolution of the two diseases in the absence of treatment (natural history) [7,8] and the results in terms of disease control of the clinical management of the two premalignant lesions (clinical outcomes) [1].…”