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Human papillomavirus 16 L1 gene methylation as a potential biomarker for predicting anal intraepithelial neoplasia in men who have sex with men (MSM).

ABSTRACT: The human papillomavirus (HPV) 16 early promoter and L1 gene methylation were quantitatively measured using pyrosequencing assay in anal cells collected from men who have sex with men (MSM) to determine potential biomarkers for HPV-related anal cancer. The methylation patterns of HPV16 genes, including the early promoter (CpG 31, 37, 43, 52, and 58) and L1 genes (CpG 5600, 5606, 5609, 5615, 7136, and 7145), were analyzed in 178 anal samples. The samples were diagnosed as normal, anal intraepithelial neoplasia (AIN) 1, AIN2, and AIN3. Low methylation levels of the early promoter (< 10%) and L1 genes (< 20%) were found in all detected normal anal cells. In comparison, medium to high methylation (≥ 20-60%) in the early promoter was found in 1.5% (1/67) and 5% (2/40) of AIN1 and AIN2-3 samples, respectively. Interestingly, slightly increased L1 gene methylation levels (≥ 20-60%), especially at the HPV16 5'L1 regions CpGs 5600 and 5609, were demonstrated in AIN2-3 specimen. Moreover, a negative correlation between high HPV16 L1 gene methylation at CpGs 5600, 5609, 5615, and 7145 and a percentual CD4 count was found in AIN3 HIV positive cases. When comparing the methylation status of AIN2-3 to that of normal/AIN1 lesions, the results indicated the potential of using HPV16 L1 gene methylation as a biomarker for HPV-related cancer screening.

SUBMITTER: Chaiwongkot A

PROVIDER: S-EPMC8409669 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We examined the long-term clinical and economic benefits of quadrivalent human papillomavirus (qHPV) vaccine as a secondary/adjunct prevention strategy in the prevention of recurrent high-grade intraepithelial neoplasia (HGAIN) in HIV-negative men who have sex with men (MSM) and are 27 years or older. We constructed a Markov model to evaluate the clinical effectiveness and cost-effectiveness of two strategies: (1) no qHPV vaccine after treatment for HGAIN versus (2) qHPV vaccine after treatment for HGAIN. Model parameters, including natural history of anal cancer, vaccine efficacy measured in terms of hazard ratio (HR) (decrease in the risk of recurrent HGAIN), HGAIN treatment efficacy, utilities, and costs, were obtained from the literature. The outcomes were measured in terms of lifetime risk of anal cancer, lifetime cost, quality-adjusted life years, and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted on all model parameters. We found that vaccinating HIV-negative MSM reduced the lifetime risk of anal cancer by 60.77% at an ICER of US$87,240 per quality-adjusted life-year. The results were highly sensitive to vaccine efficacy, transition of HGAIN to anal cancer, cost of treatment for HGAIN, vaccine degree of protection over time, and the vaccine duration of protection and less sensitive to HPV clearance, cost of qHPV vaccine, and the transitions from normal to low-grade anal intraepithelial neoplasia (LGAIN) and normal to HGAIN. With an HR of 0.3, the ICER was well below a $50,000 willingness-to-pay threshold; with an HR of 0.5, the ICER was still below a threshold of $100,000. The most critical disease-related factor influencing the cost-effectiveness was the progression of HGAIN to anal cancer. At an annual transition probability below 0.001, the ICER was below $50,000. Vaccinating HIV-negative MSM treated for HGAIN decreases the lifetime risk of anal cancer and is likely to be a cost-effective intervention.

Project description:BACKGROUND:The aim of the present study was to evaluate patient factors that affect the progression of anal dysplasia in human immunodeficiency virus (HIV)-positive individuals. METHODS:A retrospective cohort study of HIV-positive adults with human papilloma virus related anal lesions was performed from 2012 to 2017. All patients underwent surgical excision or biopsy and fulguration of lesions in the operating room without using high resolution anoscopy. Patients with initial presentation of squamous cell carcinoma were excluded. The study was designed to investigate progression between the first available histology and either the follow up histology or a negative examination. Patient files were reviewed and data was collected. A bivariate analysis of continuous and categorical variables was performed. RESULTS:One hundred and sixty-one patients met the inclusion criteria. Ninety-seven percent were male. Mean age was 41 years. Thirty-five percent were African American and 47% were Caucasian. After a median follow-up interval of 331 days (IQR 120-615 days) 14 (9%) of patients had progression of disease. Visible lesions on initial presentation, as opposed to lesions found in patients undergoing examination under anesthesia because of HSIL on anal pap smear, was associated with progression (p = 0.0.2). A lower initial CD4 count (p?=?0.01) and initial surgical pathology of anal condylomata (p?=?0.01) were also associated with progression. High-risk serotype was associated with no change or regression (p?=?0.01). CONCLUSIONS:In our large cohort of HIV-positive patients treated without high resolution anoscopy the rate of progression was low. Most notably, visible lesions at initial presentation and CD4 count when lower were associated with progression. Initial surgical pathology of anal condylomata was associated with progression, while high-risk serotypes correlated with regression or stability. Identification of risk factors has important implications concerning postoperative surveillance and counseling of HIV-positive patients with anal condylomata/ anal dysplasia.

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Human papillomavirus 16 L1 gene methylation as a potential biomarker for predicting anal intraepithelial neoplasia in men who have sex with men (MSM).

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