Anal Intraepithelial Neoplasia 2NCT06327568
Anal Cancer and/or Precancer Screening: Performance Analysis of the BD Onclarity™ HPV Assay on Anal Specimens
An observational study of Anal Intraepithelial Neoplasia 2 and Anal Intraepithelial Neoplasia 1, run by European Institute of Oncology at 1 site in Italy.
Trial summary
Human papillomavirus (HPV) infection has been implicated as a necessary cause for the development of the majority of anogenital neoplasms which represent approximately 95% of anal tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anal Intraepithelial Neoplasia 2, Anal Intraepithelial Neoplasia 1, Anal Cancer
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- 17 Jun 2022to 17 Jun 2029
- 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
- Adult, Older adult
Study population: Patients who come at the European Institute of Oncology at high risk of anal cancer undergoing cancer screening anal, colorectal, or on an outpatient basis for HPV-related pathologies.
Who may be able to join
- Subjects older than 18 years old
- Subjects with histological-confirmed high-grade anal intraepithelial neoplasia (AIN2+) or anal invasive cancer
- Subjects with histological-confirmed low-grade anal intraepithelial neoplasia (AIN1)
- Subjects at high-risk for anal cancers, including:
- Immunocompromised subjects (patients with HIV infection, or taking immunosuppressive drugs, or post-organ transplantation)
- Men who have sex with men (MSM)
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- Women aged at least 40 years with a history of cervical intraepithelial neoplasia CIN2+ and/or vulvar cancer
- Subjects affected by anal and/or peri-anal localizations of Crohn's disease
- Subjects undergoing colorectal cancer screening
- Signed written consent.
Who cannot join
- Refuse to sign written consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Cristina Mazzon contact
Italy1 site, 1 recruiting
- Recruiting
European Institute of Oncology
Milan
Fabio Bottari
Cristina Trovato, MD
About this study
Official title: Anal Cancer and/or Precancer Screening: Performance Analysis of the BD Onclarity HPV Assay on Anal Specimens
Human papillomavirus (HPV) infection has been implicated as a necessary cause for the development of the majority of anogenital neoplasms which represent approximately 95% of anal tumors. Persistent high risk HR-HPV infection promotes progression from intraepithelial lesions high-grade squamous anal tumors (AIN) (H-SIL) to invasive anal tumors.
The diagnosis of AIN is made by cytology or biopsy during routine examinations. To date, no HPV test has been clinically validated for anal specimens and none are available in the molecular diagnostics market for this purpose.
The performance analysis of an HPV Test with simultaneous genotyping on anal samples could implement anal cancer screening without an invasive procedure and with one simple approach.
Read the detailed description
Anal cancer is a rare disease in the general population, but its incidence is higher in certain at-risk groups, such as immunosuppressed individuals, including those with HIV infections and post-organ transplantation patients, men who have sex with men, and women with HPV-related lower genital tract dysplasia or cancer.
A squamous intraepithelial anal lesion is the dysplastic growth of squamous epithelial cells in the transition zone of the anal canal. This lesion is pre-malignant and can progress to anal squamous cell carcinoma if left untreated.
Human papillomavirus (HPV) infection has been implicated as the necessary cause for the development of the majority of anogenital malignancies accounting for approximately 95% of anal cancers. Persistent infection with HR-HPV promotes progression from high-grade squamous intraepithelial lesions (H-SIL) to invasive anal cancers. In the anal canal, low-grade intraepithelial lesion LSIL correlates with anal intraepithelial neoplasia (AIN)-1 or anal condyloma, while high grade squamous intraepithelial lesion HSIL correlates with AIN-2 and AIN-3.
Prevalence of H-SIL is around 40 to 50%. Progression from H-SIL to anal cancer is about 1/250 per year in HIV-positive MSM and 1/5000 per year in HIV-negative MSM, respectively.
The diagnosis of AIN is made from cytology or biopsy during routine examinations.
Up to date, different guidelines for anal cancer screening have been proposed but are not uniform. These include 1) digital ano-rectal examination, useful in unrecognized but symptomatic subjects, and 2) anal cytology, useful in asymptomatic subjects, only if high-resolution anoscopy is available.
These observations support the need to implement screening to prevent anal precancers and cancers.
At this moment, no HPV assay has been validated for anal specimens, and none is available in the molecular diagnostics market.
Validation of HPV typing methods on anal specimens could implement anal cancer screening without an invasive procedure and with an easy approach for the patient.
The BD Onclarity™ HPV Assay (BD Diagnostics, Sparks, USA) is a real-time polymerase chain reaction PCR assay that detects type-specific genomic DNA. The target of the assay is the E6 and E7 HPV genes. It simultaneously detects all 14 high-risk HPV types and can provide an "extended" genotype information on six individual genotypes (HPV 16, 18, 31, 45, 51 and 52), and in three distinct groups (33 and 58; 56, 59 and 66; and 35,39 and 68). Briefly, the DNA was extracted using BD FOX™ magnetic particles and the eluate-containing DNA was used to set up three PCR genotyping reactions: G1 detects HPV 16, HPV 18 and HPV 45 plus the internal beta globin control; G2 detects HPV 31, HPV 33_58 and HPV 56_59_66 plus the internal beta globin.
- Conditions
- Anal Intraepithelial Neoplasia 2, Anal Intraepithelial Neoplasia 1, Anal Cancer, High-Risk Cancer
- Keywords
- anal cancer, Human papillomavirus (HPV) infection, PCR genotyping, AIN 2
- Medical subject headings
- Anus Neoplasms, Papillomavirus Infections, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Case patients | Histological-confirmed high-grade anal intraepithelial neoplasia (AIN2+ and 3+) and invasive cancer; patients with macroscopic anal lesion. | |
| Control patients | Histological-confirmed low-grade anal intraepithelial neoplasia (AIN1), and subjects at high-risk for anal cancers, including: Immunocompromised subjects (patients with HIV infection, or taking immunosuppressive drugs, or post-organ transplantation); Men who have sex with men (MSM); Women aged at least 40 years with a history of CIN2+ and/or vulvar cancer; Subjects affected by anal and/or peri-anal localizations of Crohn's disease. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity and specificity of BD Onclarity HPV assay for HPV detection and genotyping in case/control patients.
To evaluate to use of BD Onclarity HPV assay for HPV detection and genotyping from the anus, without endoscope. This study aims to enroll 100 cases and 100 controls to evaluate the performance of the Onclarity test in detecting the presence of HPV in anal swab samples that will be placed in a Thin Prep vial (Hologic), in order to perform cytology and the BD Onclarity assay, a qualitative target-amplification test based on RT-PCR and fluorescent probe technology to detect E6 and E7 DNA regions of the HPV genome; Onclarity provides genotyping information on six individual genotypes (HPV 16, 18, 31, 45, 51 and 52) and reports the remaining HPV genotypes in three distinct groups (33/58, 35/39/68, and 56/59/66). The assay has an internal human beta-globin (HBB) gene control for sample adequacy and assay performance. Sensitivity, specificity of the Onclarity test will be evaluated.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2024
- Study start17 Jun 2022
- Primary completion17 Jun 2026 (estimated)
- Study completion17 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anal Intraepithelial Neoplasia 2Studies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06327568
- Sponsor's protocol ID
- IEO 1663
- Status last verified
- Mar 2024
- First submitted
- 18 Mar 2024
- Last updated
- 26 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anal Cancer and/or Precancer Screening: Performance Analysis of the BD Onclarity HPV Assay on Anal Specimens
- ClinicalTrials.gov ID
- NCT06327568
- Acronym / sponsor ID
- IEO 1663
- Conditions
- Anal Intraepithelial Neoplasia 2, Anal Intraepithelial Neoplasia 1, Anal Cancer, High-Risk Cancer
- Keywords
- anal cancer, Human papillomavirus (HPV) infection, PCR genotyping, AIN 2
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- 17 Jun 2022 (actual)
- Primary completion
- 17 Jun 2026 (estimated)
- Study completion
- 17 Jun 2029 (estimated)
- First posted
- 25 Mar 2024 (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.
Human papillomavirus (HPV) infection has been implicated as a necessary cause for the development of the majority of anogenital neoplasms which represent approximately 95% of anal tumors. Persistent high risk HR-HPV infection promotes progression from intraepithelial lesions high-grade squamous anal tumors (AIN) (H-SIL) to invasive anal tumors.
The diagnosis of AIN is made by cytology or biopsy during routine examinations. To date, no HPV test has been clinically validated for anal specimens and none are available in the molecular diagnostics market for this purpose.
The performance analysis of an HPV Test with simultaneous genotyping on anal samples could implement anal cancer screening without an invasive procedure and with one simple approach.
Detailed description
Anal cancer is a rare disease in the general population, but its incidence is higher in certain at-risk groups, such as immunosuppressed individuals, including those with HIV infections and post-organ transplantation patients, men who have sex with men, and women with HPV-related lower genital tract dysplasia or cancer.
A squamous intraepithelial anal lesion is the dysplastic growth of squamous epithelial cells in the transition zone of the anal canal. This lesion is pre-malignant and can progress to anal squamous cell carcinoma if left untreated.
Human papillomavirus (HPV) infection has been implicated as the necessary cause for the development of the majority of anogenital malignancies accounting for approximately 95% of anal cancers. Persistent infection with HR-HPV promotes progression from high-grade squamous intraepithelial lesions (H-SIL) to invasive anal cancers. In the anal canal, low-grade intraepithelial lesion LSIL correlates with anal intraepithelial neoplasia (AIN)-1 or anal condyloma, while high grade squamous intraepithelial lesion HSIL correlates with AIN-2 and AIN-3.
Prevalence of H-SIL is around 40 to 50%. Progression from H-SIL to anal cancer is about 1/250 per year in HIV-positive MSM and 1/5000 per year in HIV-negative MSM, respectively.
The diagnosis of AIN is made from cytology or biopsy during routine examinations.
Up to date, different guidelines for anal cancer screening have been proposed but are not uniform. These include 1) digital ano-rectal examination, useful in unrecognized but symptomatic subjects, and 2) anal cytology, useful in asymptomatic subjects, only if high-resolution anoscopy is available.
These observations support the need to implement screening to prevent anal precancers and cancers.
At this moment, no HPV assay has been validated for anal specimens, and none is available in the molecular diagnostics market.
Validation of HPV typing methods on anal specimens could implement anal cancer screening without an invasive procedure and with an easy approach for the patient.
The BD Onclarity™ HPV Assay (BD Diagnostics, Sparks, USA) is a real-time polymerase chain reaction PCR assay that detects type-specific genomic DNA. The target of the assay is the E6 and E7 HPV genes. It simultaneously detects all 14 high-risk HPV types and can provide an "extended" genotype information on six individual genotypes (HPV 16, 18, 31, 45, 51 and 52), and in three distinct groups (33 and 58; 56, 59 and 66; and 35,39 and 68). Briefly, the DNA was extracted using BD FOX™ magnetic particles and the eluate-containing DNA was used to set up three PCR genotyping reactions: G1 detects HPV 16, HPV 18 and HPV 45 plus the internal beta globin control; G2 detects HPV 31, HPV 33_58 and HPV 56_59_66 plus the internal beta globin.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case patients | – | –Histological-confirmed high-grade anal intraepithelial neoplasia (AIN2+ and 3+) and invasive cancer; patients with macroscopic anal lesion. |
| Control patients | – | –Histological-confirmed low-grade anal intraepithelial neoplasia (AIN1), and subjects at high-risk for anal cancers, including: Immunocompromised subjects (patients with HIV infection, or taking immunosuppressive drugs, or post-organ transplantation); Men who have sex with men (MSM); Women aged at least 40 years with a history of CIN2+ and/or vulvar cancer; Subjects affected by anal and/or peri-anal localizations of Crohn's disease. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients who come at the European Institute of Oncology at high risk of anal cancer undergoing cancer screening anal, colorectal, or on an outpatient basis for HPV-related pathologies.
Key inclusion criteria (10 listed)
- Subjects older than 18 years old
- Subjects with histological-confirmed high-grade anal intraepithelial neoplasia (AIN2+) or anal invasive cancer
- Subjects with histological-confirmed low-grade anal intraepithelial neoplasia (AIN1)
- Subjects at high-risk for anal cancers, including:
- Subjects undergoing colorectal cancer screening
Key exclusion criteria (1 listed)
- Refuse to sign written consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Sensitivity and specificity of BD Onclarity HPV assay for HPV detection and genotyping in case/control patients.
Time frame: 4 years
To evaluate to use of BD Onclarity HPV assay for HPV detection and genotyping from the anus, without endoscope. This study aims to enroll 100 cases and 100 controls to evaluate the performance of the Onclarity test in detecting the presence of HPV in anal swab samples that will be placed in a Thin Prep vial (Hologic), in order to perform cytology and the BD Onclarity assay, a qualitative target-amplification test based on RT-PCR and fluorescent probe technology to detect E6 and E7 DNA regions of the HPV genome; Onclarity provides genotyping information on six individual genotypes (HPV 16, 18, 31, 45, 51 and 52) and reports the remaining HPV genotypes in three distinct groups (33/58, 35/39/68, and 56/59/66). The assay has an internal human beta-globin (HBB) gene control for sample adequacy and assay performance. Sensitivity, specificity of the Onclarity test will be evaluated.
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 26 Mar 2024.
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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.
Cristina Mazzon contact
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 Intraepithelial Neoplasia 2 and Anal Intraepithelial Neoplasia 1, run by European Institute of Oncology at 1 site in Italy.
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 10 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: looking for participants now, as of the sponsor's last update on 26 Mar 2024. 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 Italy. 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?
Contact Fabio Bottari (+390294372716, fabio.bottari@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity and specificity of BD Onclarity HPV assay for HPV detection and genotyping in case/control patients. (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Mar 2024.