Anal cytological lesions and HPV infection in individuals at increased risk for anal cancer

BACKGROUND: The effect of antiretroviral therapy (ART) on the natural history of anal HR-HPV and anal lesion progression is not well established. We reviewed the association of ART and other HIV-related factors on anal HPV infection, anal intraepithelial neoplasia (AIN), and anal cancer among people living with HIV (PLHIV). METHODS: We searched Medline and Embase for studies from 1 January 1996 to 30 October 2019 that reported the association of HIV-related exposures (ART, HIV-RNA plasma viral load [PVL] and nadir or current CD4+ cell count) with outcomes of anal HR-HPV prevalence, incidence or persistence or prevalence, incidence, progression or regression of anal histological/cytological abnormalities, or anal cancer incidence. We assessed the risk of bias of included studies using the Newcastle-Ottawa scale. We performed random-effects meta-analyses; heterogeneity was examined using I 2 statistic. FINDINGS: 122 studies were included comprising 417,006 PLHIV (19%, 44% and 5% women, men-whohave-sex-with-men; men-who-have-sex-with-women, respectively; 32% of studies did not stratify findings by gender and/or sexual orientation). PLHIV taking ART had 35% lower HR-HPV prevalence compared to ART-naïve (crude Odds Ratio[cOR]=0.65, 95%CI:0.54-0.79; I 2 =12.1%) in 18 studies and prolonged ART use was associated with a 10% reduction in HR-HPV prevalence in two studies (per year: aOR=0.90, 95%CI:0.85-0.95, I 2 =0.0%). PLHIV with undetectable PVL had lower HSIL/AIN2+ prevalence compared to those without (cOR=0.84, 95%CI:0.72-0.98, I 2 =0.0%) in 16 studies, particularly if sustained for >1 year (cOR=0.62, 95%CI:0.47-0.81, I 2 =0.0%). ART was not associated with anal cancer incidence when adjusted for years living with HIV in 3 studies (aHR=1.11, 95%CI: 0.68-1.80, I 2 =0.0%), but ART users with sustained undetectable HIV PVL had 44% lower risk of anal cancer compared to those without (aHR=0.56, 95%CI:0.44-0.70, I 2 =0%) and for each 100 cells/µl increase in nadir CD4+ count, there was a 40% decrease in anal cancer incidence (cHR=0.60, 95%CI:0.46-0.78, I 2 =21.7%). INTERPRETATION: Effective ART use and early initiation at higher nadir CD4+ may reduce anal HR-HPV and anal cancer risk.

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“…ART vs. ART naïve (26, 27, 32-35, 102-104, 107-112, 116-122, 124 Nadir CD4+ ≥200 vs. <200 cells/µl (27,102,105,106,108…”

Section: Ascus-ain1+ Prevalencementioning

confidence: 99%

Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia, and anal cancer in people living with HIV: a systematic review and meta-analysis

et al. 2020

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“…A recent study by Dona et al reported lower CD4 counts and CD4 nadir in patients with anal dysplasia, but these parameters were without statistical significance . Multiple studies have examined and reported a correlation between these parameters and anal dysplasia .…”

Section: Discussionmentioning

confidence: 99%

“…In 2017, there were approximately 8200 new cases with approximately 1100 deaths reported in the United States, and the disease is more common in women than men, with a ratio of 1.8:1 . Both HIV‐positive (HIV+) and HIV‐negative (HIV‐) individuals with high‐risk HPV infection, in particular HPV types 16/18, were found to be 2 to 4 times more likely to have cytological lesions compared with those who were negative for these genotypes . An HPV infection is prevalent, and approximately 90% of people living with HIV (PLWH) also are HPV positive.…”

Section: Introductionmentioning

confidence: 99%

Importance of anal cytology and screening for anal dysplasia in individuals living with HIV with an emphasis on women

Cimic

Wilkin

Heymann

et al. 2019

Cancer Cytopathology

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BACKGROUND:The incidence of squamous cell carcinoma of the anal canal has been increasing in high-risk populations.To the authors' knowledge, there is no international consensus regarding screening for squamous cell carcinoma of the anal canal, but screening is commonly comprised of a Papanicolaou (Pap) test in combination with digital anorectal examination followed by high-resolution anoscopy if necessary. The current study focused on individuals living with HIV and particularly on women living with HIV. METHODS: In this 5-year retrospective study, the authors identified 5982 Pap tests, 1848 of which had follow-up biopsy within 6 months. The rate of atypical squamous cells of undetermined significance was 42%, and approximately 38.1% of cases with this interpretation were diagnosed as high-grade squamous intraepithelial lesions on follow-up biopsy. In addition, 82 women with anal cytology had long-term follow-up (>10 years) available. RESULTS: The authors investigated a relationship between cervicovaginal human papillomavirus (HPV) results, cervical pathology, CD4 T-cell count, and CD4/8 ratio with the anal cytology interpretation. A statistical correlation was noted between the CD4 count and the CD4/8 ratio and the presence of anal dysplasia. Nearly one-half of the women without cervicovaginal HPV positivity presented with anal dysplasia. CONCLUSIONS: The results of the current study demonstrated that, among women living with HIV, screening for anal dysplasia should not be eschewed, regardless of lower genital tract pathology and/or HPV status. To the authors' knowledge, the current study is the largest reported retrospective anal cytology cohort in individuals living with HIV.

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“…Another limitation is that the presence and effect of low-risk HPV types could not be evaluated with the genotyping test used in our study. However, although it has been suggested that low-risk HPV types may have a role in the appearance of anal lesions, the risk of low-risk HPV infection in the development and progression of anal premalignancies is clearly lower than the risk due to high-risk HPV infection [44,45].…”

Section: Discussionmentioning

confidence: 99%

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

Pino

Martí

Gaber³

et al. 2019

Diagnostics

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There is growing interest in anal cancer screening strategies. However, cytological/molecular evaluation of anal samples is challenging. We aimed to determine the feasibility of detecting, in anal liquid-based cytologies, the expression of biomarkers involved in the cell cycle disturbance elicited by human papillomavirus (HPV). The accuracy of this approach in the identification of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia grade2–3 (HSIL/AIN2–3) was also evaluated. 215 anal cytologies from men having sex with men living with human immunodeficiency virus were evaluated. Patients showing concordant cytological and anoscopy-directed biopsy diagnosis were selected: 70 with negative cytology and HPV test, 70 with low-grade SIL (LSIL/AIN1) cytology and biopsy, and 75 with cytology and biopsy of HSIL/AIN2–3. CDKN2A/p16, MKI67 and TOP2A mRNA expression was analyzed. HPV detection was performed with Xpert HPV Assay (Cepheid, Sunnyvale, CA, USA). HSIL/AIN2–3 showed higher expression for the biomarkers than LSIL/AIN1 or negative samples. The specificity for HSIL/AIN2–3 detection for a sensitivity established at 70% was 44.7% (95%confidence interval [CI] 36.5–53.2) for TOP2A and MKI67 and 54.5% (95%CI 46.0–62.8%) for CDKN2A/p16. mRNA detection of cell biomarkers in anal liquid-based cytology is feasible. Further studies are warranted to confirm if strategies based on mRNA detection have any role in anal cancer screening.

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Anal cytological lesions and HPV infection in individuals at increased risk for anal cancer

Cited by 20 publications

References 44 publications

Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia, and anal cancer in people living with HIV: a systematic review and meta-analysis

Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia, and anal cancer in people living with HIV: a systematic review and meta-analysis

Importance of anal cytology and screening for anal dysplasia in individuals living with HIV with an emphasis on women

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

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