Ignite Creation Date:
2024-05-06 @ 7:16 AM
Last Modification Date:
2024-10-26 @ 11:46 AM
Study NCT ID:
NCT02503111
Status:
TERMINATED
Last Update Posted:
2022-06-13
First Post:
2015-07-10
Brief Title:
The HPV-SAVE Study Team HPV Screening and Vaccine Evaluation in Men Who Have Sex With Men
Sponsor:
University Health Network Toronto
Organization:
University Health Network Toronto
Study Overview
Official Title:
A Randomized Controlled Open-label Trial Examining the Efficacy Safety and Tolerability of Ablative Therapies for High-grade Anal Dysplasia Versus Observation Alone in HIV-positive Men Who Have Sex With Men MSM
Status:
TERMINATED
Status Verified Date:
2022-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Results from ANCHOR study showed benefit of Treatment over Surveillance in preventing anal cancer
That study was similar to the current one
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HPV-SAVE
Brief Summary:
Human papillomavirus HPV is the most common sexually transmitted infection worldwide Infection by certain high-risk oncogenic types of HPV HR-HPV is the major cause of several cancers in men notably squamous cell carcinoma SCC of the anal canal Rates of anal infection with these HR-HPV strains and the resultant high-grade anal dysplasia and anal cancer are much higher in men who have sex with men MSM than in the general population Co-infection with human immunodeficiency virus HIV further amplifies this burden making the rates of anal SCC in HIV-positive MSM higher than the historic rates of cervical cancer prior to the adoption of routine cervical cytology screening Despite these alarming statistics there are no established protocols for optimal screening and treatment of anal HPV and cancer precursors nor has there been any widespread rollout of organized screening programs anywhere in Canada Further not only does HPV directly cause significant disease in these men but there is growing epidemiologic evidence that HPV infection may enhance sexual transmission of HIV These significant knowledge gaps translate into fundamental deficiencies in care for HIV-positive MSM
The HPV Screening and Vaccine Evaluation in MSM HPV-SAVE study team will recruit a large group of MSM from various Ontario and Vancouver clinics in order to carry out a number of different studies The HPV-SAVE team brings together community and internationally-recognized experts in HPV and HIV disease and mucosal immunology to better define the optimal approaches for primary and secondary prevention and treatment of HPV-associated anal disease among HIV-positive MSM and to explore biological mechanistic evidence regarding the potential role of HPV as a co-factor for HIV transmission This will yield critical information which can lead to improvement in the health of MSM and will provide a foundation on which to build further large-scale screening and treatment trials on a national level The primary aim of the current study is to systematically compare ablative therapy versus intensive observation alone also known as watchful waiting in outcomes relating to high-grade anal dysplasia
The HPV Screening and Vaccine Evaluation in MSM HPV-SAVE study team will recruit a large group of MSM from various Ontario and Vancouver clinics in order to carry out a number of different studies The HPV-SAVE team brings together community and internationally-recognized experts in HPV and HIV disease and mucosal immunology to better define the optimal approaches for primary and secondary prevention and treatment of HPV-associated anal disease among HIV-positive MSM and to explore biological mechanistic evidence regarding the potential role of HPV as a co-factor for HIV transmission This will yield critical information which can lead to improvement in the health of MSM and will provide a foundation on which to build further large-scale screening and treatment trials on a national level The primary aim of the current study is to systematically compare ablative therapy versus intensive observation alone also known as watchful waiting in outcomes relating to high-grade anal dysplasia
Detailed Description:
Since the 1990s combination antiretroviral therapy cART has markedly reduced HIV-related opportunistic infections and mortality 1 and increased the life expectancy of people living with HIV 2 While acquired immune deficiency syndrome AIDS-defining malignancies have declined 34 non-AIDS defining malignancies continue to occur at higher rates in HIV-infected persons than in the general population 4 Amongst these are cancers associated with HPV which is responsible for the vast majority of cervical cancers itself a well-established AIDS-defining illness and an estimated 90 of SCC of the anal canal 5 cART not only fails to protect against anal pre-cancers and cancers 467 but the incidence of anal SCC is increasing in the cART era 68 Because of this increasing burden of disease there is an urgent need to find effective ways of preventing anal SCC in those living with HIV This includes screening for anal cancer precursors and ablative treatment of these lesions
Though it is infrequent at a rate of 1 per 100 000 anal SCC is on the rise in the general population 9 It occurs at significantly higher rates in HIV-positive men - particularly among men who have sex with men MSM - with an estimated rate of 60 to 160 per 100 000 4 and no evidence of slowing in the era of increased cART use 10 See Figure 1 In fact rates of anal cancer among HIV-infected MSM are comparable to rates of cervical cancer in women prior to the adoption of routine screening for cervical dysplasia 11 According to data from the Public Health Agency of Canada rates of cervical cancer in 1972 were 18 per 100 000 dropping to just under 8 per 100 000 in 2004 12 In addition to its etiologic association with HPV anal cancer shares many similarities with cervical cancer Both are squamous cell cancers occurring at the squamocolumnar junction 1314 and both likely arise from histologically-similar dysplastic precursor lesions 1516 It is postulated that a critical step in anal cancer carcinogenesis is the establishment of persistent infection with oncogenic HPV in the anal canal 16 Though the majority of HPV infections are considered transient and will eventually clear even in HIV-positive individuals 17 HIV-positive individuals have higher rates of persistent infection especially with oncogenic HPV types 18
Of the greater than 170 HPV types over 50 favour the anogenital area and on the basis of epidemiologic and phylogenetic data these have been classified by the International Agency for Research on Cancer 19 The vast majority of anal cancers as well as cervical cancers are caused by two high-risk HPV types HPV type 16 and HPV type 18 which are responsible for 66 and 5 of anal cancers respectively 20 HPV lesions caused by low-risk HPV LR-HPV types include condylomata commonly known as genital warts of which 90 are caused by HPV types 6 and 11 21 Prevention strategies for anal cancers have emerged that are analogous to strategies used in cervical cancer screening in that the aim is to identify precursor lesions which can then be removed before progression to cancer Screening and detection rely on a combination of anal cytology Papanicolaou or Pap smear anal HPV detection and high-resolution anoscopy HRA which is analogous to colposcopy Visually-directed anal biopsy during HRA is considered the gold standard for detecting dysplastic lesions such as high-grade anal intraepithelial neoplasia HGAIN typically graded as AIN-2 or -3 1622 Anal cytology is generally used as a screening test to determine whether HRA is needed however cytology is an imperfect predictor of intra-anal HGAIN Despite the clear evidence indicating the benefit of screening and treatment procedures in cervical cancer screening no large rigorous studies have been performed to assess such strategies in anal cancer prevention in men or women
Though it is infrequent at a rate of 1 per 100 000 anal SCC is on the rise in the general population 9 It occurs at significantly higher rates in HIV-positive men - particularly among men who have sex with men MSM - with an estimated rate of 60 to 160 per 100 000 4 and no evidence of slowing in the era of increased cART use 10 See Figure 1 In fact rates of anal cancer among HIV-infected MSM are comparable to rates of cervical cancer in women prior to the adoption of routine screening for cervical dysplasia 11 According to data from the Public Health Agency of Canada rates of cervical cancer in 1972 were 18 per 100 000 dropping to just under 8 per 100 000 in 2004 12 In addition to its etiologic association with HPV anal cancer shares many similarities with cervical cancer Both are squamous cell cancers occurring at the squamocolumnar junction 1314 and both likely arise from histologically-similar dysplastic precursor lesions 1516 It is postulated that a critical step in anal cancer carcinogenesis is the establishment of persistent infection with oncogenic HPV in the anal canal 16 Though the majority of HPV infections are considered transient and will eventually clear even in HIV-positive individuals 17 HIV-positive individuals have higher rates of persistent infection especially with oncogenic HPV types 18
Of the greater than 170 HPV types over 50 favour the anogenital area and on the basis of epidemiologic and phylogenetic data these have been classified by the International Agency for Research on Cancer 19 The vast majority of anal cancers as well as cervical cancers are caused by two high-risk HPV types HPV type 16 and HPV type 18 which are responsible for 66 and 5 of anal cancers respectively 20 HPV lesions caused by low-risk HPV LR-HPV types include condylomata commonly known as genital warts of which 90 are caused by HPV types 6 and 11 21 Prevention strategies for anal cancers have emerged that are analogous to strategies used in cervical cancer screening in that the aim is to identify precursor lesions which can then be removed before progression to cancer Screening and detection rely on a combination of anal cytology Papanicolaou or Pap smear anal HPV detection and high-resolution anoscopy HRA which is analogous to colposcopy Visually-directed anal biopsy during HRA is considered the gold standard for detecting dysplastic lesions such as high-grade anal intraepithelial neoplasia HGAIN typically graded as AIN-2 or -3 1622 Anal cytology is generally used as a screening test to determine whether HRA is needed however cytology is an imperfect predictor of intra-anal HGAIN Despite the clear evidence indicating the benefit of screening and treatment procedures in cervical cancer screening no large rigorous studies have been performed to assess such strategies in anal cancer prevention in men or women
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None