The World Health Organization (WHO) has updated its guidelines for cervical cancer prevention, now including dual-stain cytology with the CINtec PLUS Cytology test. This update aims to improve the identification of individuals at higher risk of developing cervical precancer and cancer.
CINtec PLUS Cytology received FDA approval and CE marking as a test designed to identify human papillomavirus (HPV)-positive individuals who are most at risk of developing cervical precancer and cancer. The test detects the presence of both p16 and KI-67 in a cell, biomarkers that indicate a cell is undergoing transformation and could become cancerous. Identifying these patients allows for appropriate management and intervention.
ASCCP's Recommendation
In March 2024, the American Society for Colposcopy and Cervical Pathology (ASCCP) also included CINtec PLUS Cytology as a triage test for HPV-positive individuals in its updated cervical cancer screening guidelines. The guidelines recommend immediate colposcopy for patients with a positive dual-stain test. Those with a negative test may undergo retesting to determine if the infection and risk of precancer or cancer have been eliminated, potentially reducing unnecessary colposcopies.
Roche's Perspective
"Adding dual-stain cytology to the WHO guidelines further reinforces the value of our biomarker-based CINtec PLUS Cytology test to identify patients with an elevated risk of cervical cancer," said Matt Sause, chief executive officer of Roche Diagnostics. "HPV infections can cause cervical cancer, a potentially deadly disease that is highly preventable. Consequently, it is critical to determine who is most at risk."
The IMPACT Trial
The dual-stain test, along with Roche’s cervical cancer portfolio, was evaluated in the IMPACT trial, a prospective, multicenter, cervical cancer screening study conducted in the United States. The trial enrolled 35,263 women between 25 and 65 years of age undergoing routine cervical cancer screening. Participants received liquid-based cytology and two PCR-based tests for high-risk HPV. Cervical biopsy and colposcopy were performed on women with abnormal Pap cytology, those positive for high-risk HPV per either of the PCR-based tests, and a random subset of women with negative Pap cytology and HPV tests.
The study excluded women who were pregnant, those without an intact uterus, and those unwilling to undergo a colposcopy or biopsy if necessary. Exclusion criteria also included treatment for cervical intraepithelial neoplasia (CIN) in the 12 months prior to the study, or enrollment/planned enrollment in another cervical cancer screening study, an HPV treatment study, or an HPV vaccine study.
In total, 34,914 enrolled patients met the study’s eligibility criteria, and 34,807 were evaluable following valid Pap cytology and 6800/8800 HPV test results.
Key Findings from IMPACT
Findings showed that the prevalence of atypical squamous cells of undetermined significance was 6.5%, and the rate of worse-than-atypical squamous cells of undetermined significance was 3.2%. High-risk HPV, HPV16, and HPV18 were reported at rates of 15.1%, 3.1%, and 1.4%, respectively.
In women who underwent colposcopy and biopsy, grade 2 or higher CIN was reported in 8.8% of participants, and grade 3 or higher CIN occurred in 3.6% of enrolled women. In women who tested positive for HPV16, the baseline and 1-year cumulative risks for grade 3 or higher CIN were 13.6% and 16.9%, respectively. Notably, women who tested negative for HPV had a 1-year cumulative risk of grade 3 or higher CIN of 0.06%.
The IMPACT trial included a diverse patient population, with 21% Black, 24% Hispanic-Latino, and 0.3% American Indian or native Alaskan participants.
