Early Diagnosis of High-grade Serous Epithelial Ovarian Cancer Through the Analysis of DNA Derived From Pap Test Smear.

Fondazione Policlinico Universitario Agostino Gemelli IRCCS260 enrolled

Overview

Ovarian cancer is the leading cause of death among gynecological malignancies. No screening test is available for this tumor. Serous Tubal Intraepithelial Carcinoma (STIC) is the precursor lesion of the high grade serous ovarian cancer (HGSOC). Preliminary data suggest that tumor cells from STIC shed into the luminal space to reach the cervix and identical molecular alterations can be identified in the STIC and pap smears taken several years before the diagnosis. Early diagnosis could be achieved by detecting tumor components in cervical smears. This prospective/retrospective project plans to enroll high risk, germline mutated women submitted to risk reducing annessiectomy to compare the concordance of molecular alterations between tubal specimens and DNA from Pap test in order to validate a possible screening test with potential impact in reducing cancer mortality. Moreover, the evaluation of the influence of tumor micro environment in the progression from STIC to HGSOC will be studied.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

260

Conditions

Germline Mutations

Interventions

Eligibility

Sex: FEMALEMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with germline mutations candidate to prophylactic surgery RRSO (risk-reducing salpingo- oophorectomy) or RRS (risk-reducing salpingectomy) * Able and willing to sign informed consent Exclusion Criteria: * Germline mutated patients unwilling to join the trial and non-compliant with trial procedures

Outcomes

Primary Outcomes

NGS-Based Detection of Tubal Precancerous Lesions Using Pap Test DNA

To assess the concordance between the evidence of precancerous/cancerous tubal lesions and the results of NGS analysis in pDNA derived from Pap test smears longitudinally collected before prophylactic surgery. This aim would assess whether large genomic aberrations in pDNA are a predictive biomarker for the presence of STIC or tubal precancerous lesions and could be used for early detection of HGSOC.

Time frame: 1 year

Secondary Outcomes

Tumor Microenvironment in STIC-to-HGSOC Progression

To define the role of tumor microenvironment (TME) in patho-oncogenic process of the neoplastic transformations from STIC to HGSOC.