Anal Squamous Intraepithelial NeoplasiaSeVIHanalNCT03713229
Seville Cohort of People Living With HIV at Risk for Anal Cancer
An observational study of Anal Squamous Intraepithelial Neoplasia, run by Hospitales Universitarios Virgen del Rocío at 1 site in Spain.
Trial summary
There is increasing awareness of augmenting risk of anal cancer in people living with HIV, especially among men who have sex with men (MSM). High resolution anoscopy (HRA) represents the gold standard to detect pre-cancerous anal high-grade squamous intraepithelial lesions (HSIL), however, the procedure is… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anal Squamous Intraepithelial Neoplasia
- What is being tested?
- Screening for anal squamous intraepithelial lesions
- How many people
- 3,000 participants
- Where
- 1 siteSpain
- Study dates
- 1 Sep 2010to 31 Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HIV-infected patients seen at the sexually transmitted diseases/HPV consultancy of the Infectious Diseases Unit of the Virgen del Rocío Hospital in Seville, Spain.
Who may be able to join
- HIV infection as confirmed by ELISA and western blot
Who cannot join
- Unable to provide informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Study to Screen for Anal Precancerous Squamous Intraepithelial Lesions and to Prevent Anal Cancer in a Real-life Setting of People Living With HIV at Different Risk: the Seville HIV Anal Cohort
There is increasing awareness of augmenting risk of anal cancer in people living with HIV, especially among men who have sex with men (MSM). High resolution anoscopy (HRA) represents the gold standard to detect pre-cancerous anal high-grade squamous intraepithelial lesions (HSIL), however, the procedure is time-consuming, costly and, most importantly, the learning curve is very flat. This yields a poor implementation of anal screening and, likely, to an excess of otherwise preventable anal cancer. Other screening methods include digital ano-rectal examination, anal-rectal cytology and human papillomavirus (HPV) genotyping, since infection with high-risk HPV genotypes has been identified as the main reason for the development of HSIL. To date, there is no consensus in screening strategies. Furthermore, it remains unclear whether, in whom and to which extend the currently available topic and invasive treatment options for HSIL should be applied, given that the natural history of the development of anal cancer remains poorly understood. The present cohort study aims to provide real-life data on the screening, management and follow-up of HIV-infected MSM is warranted for a better understanding of anal cancer in this setting.
Read the detailed description
The development of anal precancerous squamous intraepithelial lesions (SIL) and cancer of the anus is mainly caused by infection with high-risk human papillomavirus genotypes (HR-HPV). There is increasing awareness of marked (40 to 130-fold) risk of anal cancer in people living with HIV, especially among men who have sex with men (MSM). With the changing scenario of comorbidities in the HIV-infected population, given the success of modern antiretroviral therapy, anal cancer has emerged as a leading neoplasia across different cohorts in Western countries. In 2014, almost 30000 people were newly diagnosed with HIV in Europe, the majority of cases (77%) being men. This was largely driven by HIV transmission between MSM, which accounted for 42% of all HIV diagnoses. Hence, the incidence of anal cancer is likely to increase in the years to come.
The number of experts who support the necessity of implementing wide programs of anal cancer screening in at-risk populations is rapidly growing. Indeed, both the European Guidelines for treatment of HIV-infected adults and the Guidelines of the Spanish AIDS Society (GESIDA) currently recommend the screening of anal cancer in HIV-infected subjects at risk. It is likely that in years to come, a general recommendation to screen for anal cancer in patients with different conditions associated with immunosuppression is established, as experienced in other populations. In this context, since HIV-negative MSM and women with a history of anogenital dysplasia, as well as transplant patients, exhibit excess risk of anal cancer, these populations have been typically screened in center with ongoing anal cancer screening programs.
Digital ano-rectal examination (DARE) is mainly accepted as the first screening procedure for anal high-risk SIL (HSIL), followed by anal-rectal cytology. Both represent simple methods, however, cytology shows an alarmingly low negative predictive value and furthermore, in case of an abnormal cytology, the patient is referred to high resolution anoscopy (HRA) for biopsy of acetowhite lugol-negative lesions in the anal epithelium, suggestive of HSIL. HRA performance is similar to cervical colposcopy, but unfortunately, the training process is by far longer, hampering its implementation and availability to highly-specialized centers with large cohorts of people living with HIV under care.
Although histological HSIL was identified as precursor of anal cancer, it remains unclear if, which and in whom treatment is indicated, since not all patients progress, a considerable proportion even regresses spontaneously and recurrence rates are high. Treatments currently available include topical imiquimod or 5-fluorouracil, as well as surgical treatment. Due to the lack of data, no consensus of HSIL management has been reached.
Taken together what was mentioned above, real-life data on the screening, management and follow-up of HIV-infected MSM is warranted for a better understanding of anal cancer in this setting.
- Conditions
- Anal Squamous Intraepithelial Neoplasia
- Being tested
- Screening for anal squamous intraepithelial lesions
- Keywords
- anal squamous intraepithelial lesions, anal squamous cell carcinoma, high-resolution anoscopy, liquid-based cytology, human papillomavirus, men who have sex with men, HIV infection, diagnostic performance
- Medical subject headings
- Anus Neoplasms, Homosexuality, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Screening for anal squamous intraepithelial lesionsDiagnostic test
digital-anorectal exam, liquid-based cytology, human papillomavirus testing, high-resolution anoscopy
| Study group | Role | What they receive |
|---|---|---|
| HIV-infected men who have sex with men | HIV-infected male patients who refer to conducting sexual risk practices that enable HPV transmission Receives: Diagnostic Test: Screening for anal squamous intraepithelial lesions | |
| HIV-infected men | HIV-infected male patients who neglect conducting sexual risk practices that enable HPV transmission Receives: Diagnostic Test: Screening for anal squamous intraepithelial lesions | |
| HIV-infected women | HIV-infected female patients disregarding sexual risk practices Receives: Diagnostic Test: Screening for anal squamous intraepithelial lesions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of anal HSIL
The proportion of patients with cancer of the anal squamous intraepithelial cells stage 0, defined as anal high-risk squamous intraepithelial lesions (HSIL) according to the Lower Anogenital Squamous Terminology.
Measured: 2007-2025
Incidence of anal cancer
Incidence rates per person-years of cancer of the anal squamous intraepithelial cells stage 1-4 observed over time as defined by the National Cancer Institute of the National Institutes of Health, US Department of Health and Human Services (www.cancer.gov).
Measured: 2007-2025
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2018
- Study start1 Sep 2010
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Anal Squamous Intraepithelial NeoplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 3,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospitales Universitarios Virgen del Rocío
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Biomedicina de Sevilla
- Responsible party
- Principal investigator, Karin Neukam, Hospitales Universitarios Virgen del Rocío
- Investigators
- Pompeyo Viciana, MD, PhD, Study director, Clínica El SurKarin Neukam, PharmD, PhD, Study chair, Hospitales Universitarios Virgen del RocíoCésar Sotomayor de la Piedra, Principal investigator, Hospitales Universitarios Virgen del Rocío
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03713229
- Sponsor's protocol ID
- SeVIHanal Cohort
- Acronym
- SeVIHanal
- Status last verified
- Sep 2023
- First submitted
- 18 Oct 2018
- Last updated
- 22 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Wei F, Gaisa MM, D'Souza G, Xia N, Giuliano AR, Hawes SE, Gao L, Cheng SH, Dona MG, Goldstone SE, Schim van der Loeff MF, Neukam K, Meites E, Poynten IM, Dai J, Combes JD, Wieland U, Burgos J, Wilkin TJ, Hernandez AL, Iribarren Diaz M, Hidalgo-Tenorio C, Valencia Arredondo M, Nyitray AG, Wentzensen N, Chow EP, Smelov V, Nowak RG, Phanuphak N, Woo YL, Choi Y, Hu Y, Schofield AM, Woestenberg PJ, Chikandiwa AT, Hickey AC, de Pokomandy A, Murenzi G, Pere H, Del Pino M, Ortiz AP, Charnot-Katsikas A, Liu X, Chariyalertsak S, Strong C, Ong JJ, Yunihastuti E, Etienney I, Ferre VM, Zou H, Segondy M, Chinyowa S, Alberts CJ, Clifford GM. Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies. Lancet HIV. 2021 Sep;8(9):e531-e543. doi: 10.1016/S2352-3018(21)00108-9. Epub 2021 Jul 30.
PubMed 34339628Milanes Guisado Y, Sotomayor C, Fontillon M, Dominguez Castano A, Espinosa N, Roca C, Lopez-Cortes LF, Viciana P, Neukam K; SeVIHanal Study Group. Incidence Rate and Risk Factors for Anal Squamous Cell Carcinoma in a Cohort of People Living With HIV from 2004 to 2017: Implementation of a Screening Program. Dis Colon Rectum. 2022 Jan 1;65(1):28-39. doi: 10.1097/DCR.0000000000002218.
PubMed 34694279Viciana P, Milanes-Guisado Y, Fontillon M, Dominguez Castano A, Sotomayor C, Espinosa N, Lopez-Cortes LF, Neukam K. High-risk Human Papilloma Virus Testing Improves Diagnostic Performance to Predict Moderate- to High-grade Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus-infected Men Who Have Sex With Men in Low-to-Absent Cytological Abnormalities. Clin Infect Dis. 2019 Nov 27;69(12):2185-2192. doi: 10.1093/cid/ciz144.
PubMed 30770528Neukam K, Milanes Guisado Y, Fontillon M, Merino L, Sotomayor C, Espinosa N, Lopez-Cortes LF, Viciana P; SeVIHanal Study Group. High-resolution anoscopy in HIV-infected men: Assessment of the learning curve and factors that improve the performance. Papillomavirus Res. 2019 Jun;7:62-66. doi: 10.1016/j.pvr.2019.01.003. Epub 2019 Feb 1.
PubMed 30716543
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Screen for Anal Precancerous Squamous Intraepithelial Lesions and to Prevent Anal Cancer in a Real-life Setting of People Living With HIV at Different Risk: the Seville HIV Anal Cohort
- ClinicalTrials.gov ID
- NCT03713229
- Acronym / sponsor ID
- SeVIHanal / SeVIHanal Cohort
- Conditions
- Anal Squamous Intraepithelial Neoplasia
- Keywords
- anal squamous intraepithelial lesions, anal squamous cell carcinoma, high-resolution anoscopy, liquid-based cytology, human papillomavirus, men who have sex with men, HIV infection, diagnostic performance
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- Hospitales Universitarios Virgen del RocíoUniversity, hospital or other
- Collaborators
- Instituto de Biomedicina de Sevilla
- Study start
- 1 Sep 2010 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 19 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There is increasing awareness of augmenting risk of anal cancer in people living with HIV, especially among men who have sex with men (MSM). High resolution anoscopy (HRA) represents the gold standard to detect pre-cancerous anal high-grade squamous intraepithelial lesions (HSIL), however, the procedure is time-consuming, costly and, most importantly, the learning curve is very flat. This yields a poor implementation of anal screening and, likely, to an excess of otherwise preventable anal cancer. Other screening methods include digital ano-rectal examination, anal-rectal cytology and human papillomavirus (HPV) genotyping, since infection with high-risk HPV genotypes has been identified as the main reason for the development of HSIL. To date, there is no consensus in screening strategies. Furthermore, it remains unclear whether, in whom and to which extend the currently available topic and invasive treatment options for HSIL should be applied, given that the natural history of the development of anal cancer remains poorly understood. The present cohort study aims to provide real-life data on the screening, management and follow-up of HIV-infected MSM is warranted for a better understanding of anal cancer in this setting.
Detailed description
The development of anal precancerous squamous intraepithelial lesions (SIL) and cancer of the anus is mainly caused by infection with high-risk human papillomavirus genotypes (HR-HPV). There is increasing awareness of marked (40 to 130-fold) risk of anal cancer in people living with HIV, especially among men who have sex with men (MSM). With the changing scenario of comorbidities in the HIV-infected population, given the success of modern antiretroviral therapy, anal cancer has emerged as a leading neoplasia across different cohorts in Western countries. In 2014, almost 30000 people were newly diagnosed with HIV in Europe, the majority of cases (77%) being men. This was largely driven by HIV transmission between MSM, which accounted for 42% of all HIV diagnoses. Hence, the incidence of anal cancer is likely to increase in the years to come.
The number of experts who support the necessity of implementing wide programs of anal cancer screening in at-risk populations is rapidly growing. Indeed, both the European Guidelines for treatment of HIV-infected adults and the Guidelines of the Spanish AIDS Society (GESIDA) currently recommend the screening of anal cancer in HIV-infected subjects at risk. It is likely that in years to come, a general recommendation to screen for anal cancer in patients with different conditions associated with immunosuppression is established, as experienced in other populations. In this context, since HIV-negative MSM and women with a history of anogenital dysplasia, as well as transplant patients, exhibit excess risk of anal cancer, these populations have been typically screened in center with ongoing anal cancer screening programs.
Digital ano-rectal examination (DARE) is mainly accepted as the first screening procedure for anal high-risk SIL (HSIL), followed by anal-rectal cytology. Both represent simple methods, however, cytology shows an alarmingly low negative predictive value and furthermore, in case of an abnormal cytology, the patient is referred to high resolution anoscopy (HRA) for biopsy of acetowhite lugol-negative lesions in the anal epithelium, suggestive of HSIL. HRA performance is similar to cervical colposcopy, but unfortunately, the training process is by far longer, hampering its implementation and availability to highly-specialized centers with large cohorts of people living with HIV under care.
Although histological HSIL was identified as precursor of anal cancer, it remains unclear if, which and in whom treatment is indicated, since not all patients progress, a considerable proportion even regresses spontaneously and recurrence rates are high. Treatments currently available include topical imiquimod or 5-fluorouracil, as well as surgical treatment. Due to the lack of data, no consensus of HSIL management has been reached.
Taken together what was mentioned above, real-life data on the screening, management and follow-up of HIV-infected MSM is warranted for a better understanding of anal cancer in this setting.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HIV-infected men who have sex with men | – | Diagnostic Test: Screening for anal squamous intraepithelial lesionsHIV-infected male patients who refer to conducting sexual risk practices that enable HPV transmission |
| HIV-infected men | – | Diagnostic Test: Screening for anal squamous intraepithelial lesionsHIV-infected male patients who neglect conducting sexual risk practices that enable HPV transmission |
| HIV-infected women | – | Diagnostic Test: Screening for anal squamous intraepithelial lesionsHIV-infected female patients disregarding sexual risk practices |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HIV-infected patients seen at the sexually transmitted diseases/HPV consultancy of the Infectious Diseases Unit of the Virgen del Rocío Hospital in Seville, Spain.
Key inclusion criteria (1 listed)
- HIV infection as confirmed by ELISA and western blot
Key exclusion criteria (1 listed)
- Unable to provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Screening for anal squamous intraepithelial lesionsdigital-anorectal exam, liquid-based cytology, human papillomavirus testing, high-resolution anoscopy | Diagnostic test | HIV-infected men, HIV-infected men who have sex with men, HIV-infected women |
Primary outcome
Frequency of anal HSIL
Time frame: 2007-2025
The proportion of patients with cancer of the anal squamous intraepithelial cells stage 0, defined as anal high-risk squamous intraepithelial lesions (HSIL) according to the Lower Anogenital Squamous Terminology.
Incidence of anal cancer
Time frame: 2007-2025
Incidence rates per person-years of cancer of the anal squamous intraepithelial cells stage 1-4 observed over time as defined by the National Cancer Institute of the National Institutes of Health, US Department of Health and Human Services (www.cancer.gov).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2023.
- Results publication: PubMed 34339628Wei F, Gaisa MM, D'Souza G, Xia N, Giuliano AR, Hawes SE, Gao L, Cheng SH, Dona MG, Goldstone SE, Schim van der Loeff MF, Neukam K, Meites E, Poynten IM, Dai J, Combes JD, Wieland U, Burgos J, Wilkin TJ, Hernandez AL, Iribarren Diaz M, Hidalgo-Tenorio C, Valencia Arredondo M, Nyitray AG, Wentzensen N, Chow EP, Smelov V, Nowak RG, Phanuphak N, Woo YL, Choi Y, Hu Y, Schofield AM, Woestenberg PJ, Chikandiwa AT, Hickey AC, de Pokomandy A, Murenzi G, Pere H, Del Pino M, Ortiz AP, Charnot-Katsikas A, Liu X, Chariyalertsak S, Strong C, Ong JJ, Yunihastuti E, Etienney I, Ferre VM, Zou H, Segondy M, Chinyowa S, Alberts CJ, Clifford GM. Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies. Lancet HIV. 2021 Sep;8(9):e531-e543. doi: 10.1016/S2352-3018(21)00108-9. Epub 2021 Jul 30.
- Results publication: PubMed 34694279Milanes Guisado Y, Sotomayor C, Fontillon M, Dominguez Castano A, Espinosa N, Roca C, Lopez-Cortes LF, Viciana P, Neukam K; SeVIHanal Study Group. Incidence Rate and Risk Factors for Anal Squamous Cell Carcinoma in a Cohort of People Living With HIV from 2004 to 2017: Implementation of a Screening Program. Dis Colon Rectum. 2022 Jan 1;65(1):28-39. doi: 10.1097/DCR.0000000000002218.
- Results publication: PubMed 30770528Viciana P, Milanes-Guisado Y, Fontillon M, Dominguez Castano A, Sotomayor C, Espinosa N, Lopez-Cortes LF, Neukam K. High-risk Human Papilloma Virus Testing Improves Diagnostic Performance to Predict Moderate- to High-grade Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus-infected Men Who Have Sex With Men in Low-to-Absent Cytological Abnormalities. Clin Infect Dis. 2019 Nov 27;69(12):2185-2192. doi: 10.1093/cid/ciz144.
- Results publication: PubMed 30716543Neukam K, Milanes Guisado Y, Fontillon M, Merino L, Sotomayor C, Espinosa N, Lopez-Cortes LF, Viciana P; SeVIHanal Study Group. High-resolution anoscopy in HIV-infected men: Assessment of the learning curve and factors that improve the performance. Papillomavirus Res. 2019 Jun;7:62-66. doi: 10.1016/j.pvr.2019.01.003. Epub 2019 Feb 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pompeyo Viciana, MD, PhD study director
Clínica El Sur
Karin Neukam, PharmD, PhD study chair
Hospitales Universitarios Virgen del Rocío
César Sotomayor de la Piedra principal investigator
Hospitales Universitarios Virgen del Rocío
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anal Squamous Intraepithelial Neoplasia, run by Hospitales Universitarios Virgen del Rocío at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 22 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of anal HSIL (time frame: 2007-2025). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03713229, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2023.