"Host Genome Methylation: a Screening Tool in Anal Cancer Detection"
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 770
- 试验地点
- 9
- 主要终点
- High- grade anal lesion at 3 years
研究概览
简要总结
In January 2023, the first recommendations for anal cancer screening were issued by the French National Society of Coloproctology (SNFCP). These were the world's first national recommendations for anal cancer screening for at-risk patients, not limited to people living with HIV. They are based on screening for papillomavirus type 16 (HPV16) as the first line of defence, followed by reflex cytology in the event of a positive HPV16 smear and a proctological examination. In the event of abnormal cytology or proctological examination, high-resolution anoscopy (HRA) should be performed, but access to it is limited by the number of proctologists with the expertise to carry out this examination and the cost of the equipment. The development of biological markers could enable only patients at high risk of high-grade dysplasia/anal cancer to be referred for HRA.
As part of the AIN3 cohort, we demonstrated that the markers ZNF582 and ASCL1, studied on anal smears taken when patients were included in the cohort, showed a significantly higher level of methylation in patients who subsequently progressed to anal cancer.
The aim of this project is to test, in real-life conditions, the contribution of these methylation markers in the triage of asymptomatic patients eligible for anal cancer screening according to the SNFCP guidelines (MSM over 30 years of age living with HIV, women with a history of vulvar lesions or vulvar, women patients who have had a solid organ transplant for more than 10 years and extension to men patients who have had a solid organ transplant for more than 10 years).
详细描述
I. Current state of knowledge on the pathology
In 2020, 30,000 cases of squamous cell carcinoma of the anus were reported worldwide. These cancers affect women in 2/3 of cases. They are fairly rare in the general population, with an age-standardised incidence rate of 0.35 per 100,000 person-years (p.a.) in men and 0.57 in women.
The population of men who have sex with men (MSM) living with HIV is at greater risk of anal cancer: studies in 2012 reported an 80-fold increase in the relative risk compared with the non-HIV-infected male population. This population is also more exposed to anal HPV infections, which adds to the dysimmunity associated with HIV infection. As a result, this population was already the subject of specific recommendations concerning anal canal cancer screening based on cytology. A recent meta-analysis has stratified the risk of anal cancer in different populations. It confirms the excess risk of anal cancer in the MSM population living with HIV (up to 100 per 100,000 pa in MSM living with HIV aged over 45).
It has also identified other groups at risk of anal cancer. A higher incidence rate of anal cancer in women who have already had cervical or vulvovaginal cancer is clearly established. But this meta-analysis by Clifford et al. shows a different stratification of anal cancer risk according to the type of previous HPV-induced cancer. Thus, the incidence rate of anal cancer is highest in the case of a history of vulvar cancer, equal to 50 per 100,000 pa, whereas it is close to 10 per 100,000 pa in the case of a history of vaginal or cervical cancers. Another group at risk of anal cancer is made up of immunosuppressed people not infected with HIV, and in particular solid transplant recipients, with different incidence rates of anal cancer depending on the type of transplant and above all the time since the transplant.
Overall, incidence rates of anal cancer, regardless of sex, are higher in high-income countries. In 2018, 1,532 new cases of anal cancer were reported in women in France, corresponding to an incidence rate of 2.4 per 100,000 woman-years, and 479 new cases in men, corresponding to an incidence rate of 0.8 per 100,000 man-years. As in many high-income countries, an overall increase in the incidence of this cancer has been observed in France, both in women (+3.4% and +5.7% between 1990 and 2018 and between 2010 and 2018 respectively) and in men (+1.5% and +3.3% between 1990 and 2018 and between 2010 and 2018 respectively). Trends by age for anal cancer show an increase in the number of cases, mainly in women aged 50 and 60.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (age ≥ 18 years)
- •Eligible for anal cancer screening according to the SNFCP guidelines (with extension to men who have received solid organ transplants for more than 10 years):
- •MSM (men who have sex with men) aged over 30 living with HIV
- •Patients who have received a solid organ transplant for more than 10 years
- •Women with a history of vulvar lesions or vulvar cancer
- •Non-inclusion Criteria:
- •Proctological follow-up for a current high-grade anal lesion or cancer
- •Pregnant or breastfeeding women
- •Subject deprived of liberty or under legal protection
- •Non-affiliation with social security system
- •Refusal to participate expressed by the patient
排除标准
- •Refusal of anal self-sampling on inclusion
研究组 & 干预措施
Cohort
Patient HPV16 + at inclusion :
- Cytological analysis of the smear
- Referral to proctology (recommendation): Standard proctological examination Additional self-samples will be taken at 1 year (M12), 2 years (M24) and 3 years (M36 - end of follow-up) during a visit as part of standard care Questionnaire carried out at 1 year (M12), 2 years (M24) and 3 years (M36 - end of follow-up) during a visit as part of standard care
And if cytology positive or if anal symptoms :
- Standard proctological examination
- Anal smear at clinician's discretion (virological analysis)
- Anal biopsy if necessary (cytological analysis)
- AHR (high-resolution anoscopy)
Patient HPV16 - at inclusion :
- Additional self-sampling at 3 years during a visit as part of standard care
- Questionnaire carried out at 3 years during a visit as part of standard care And if anal symptom
- Standard proctological examination, Anal smear, AHR at clinician's discretion
- Anal biopsy if necessary
干预措施: Anal self-sampling (smear) (Device)
Cohort
Patient HPV16 + at inclusion :
- Cytological analysis of the smear
- Referral to proctology (recommendation): Standard proctological examination Additional self-samples will be taken at 1 year (M12), 2 years (M24) and 3 years (M36 - end of follow-up) during a visit as part of standard care Questionnaire carried out at 1 year (M12), 2 years (M24) and 3 years (M36 - end of follow-up) during a visit as part of standard care
And if cytology positive or if anal symptoms :
- Standard proctological examination
- Anal smear at clinician's discretion (virological analysis)
- Anal biopsy if necessary (cytological analysis)
- AHR (high-resolution anoscopy)
Patient HPV16 - at inclusion :
- Additional self-sampling at 3 years during a visit as part of standard care
- Questionnaire carried out at 3 years during a visit as part of standard care And if anal symptom
- Standard proctological examination, Anal smear, AHR at clinician's discretion
- Anal biopsy if necessary
干预措施: HPV questionnaire (Behavioral)
结局指标
主要结局
High- grade anal lesion at 3 years
时间窗: 3 years after Inclusion
Analyse if methylation markers on an initial anal self sample (M0) could predict high grade anal lesion at M3
次要结局
- Persistance of HPV infection(4 years after the inclusion of the first patient)
- Rate of patients with a follow-up in accordance with French national recommendations after HPV16 positive self anal sampling(4 years after the inclusion of the first patient)
- HSIL cytology on the anal self-sample at 3 year in HPV 16 negative patients at M0(3 years after Inclusion)
- High grade anal lesion in HPV 16 positive patients at M0(1 year, 2 years, 3 years after inclusion)
- Diagnostic properties of methylation in HPV 16-positive patients at M0(M0)
- Time for HPV16 clearance(3 years after Inclusion)
- Incidence of high grade Anal lesions(3 years after Inclusion)
- Number of protocol-eligible patients refusing to participate(4 years after the inclusion of the first patient)
- Methylation levels(1 year, 2 years, 3 years after inclusion)