Clinical trial NCT06327568: Anal Cancer and/or Precancer Screening: Performance Analysis of the BD Onclarity™ HPV Assay on Anal Specimens
Official title: Anal Cancer and/or Precancer Screening: Performance Analysis of the BD Onclarity HPV Assay on Anal Specimens
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: European Institute of Oncology
Sponsor class: OTHER
First posted: 2024-03-25
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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:

  1. Immunocompromised subjects (patients with HIV infection, or taking immunosuppressive drugs, or post-organ transplantation)
  2. Men who have sex with men (MSM)
  3. Women aged at least 40 years with a history of cervical intraepithelial neoplasia CIN2+ and/or vulvar cancer
  4. Subjects affected by anal and/or peri-anal localizations of Crohn's disease
* Subjects undergoing colorectal cancer screening
* Signed written consent.

Exclusion Criteria:

* Refuse to sign written consent.

Primary outcomes:
measure: Sensitivity and specificity of BD Onclarity HPV assay for HPV detection and genotyping in case/control patients.
timeFrame: 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: European Institute of Oncology
Study officials:
References: