For physicians managing patients with cervical intraepithelial neoplasia grade 2, a new target trial emulation suggests that surveillance may reduce unnecessary excisions in selected patients without an apparent increase in short-term cancer or CIN 3+ risk.
Immediate treatment of cervical intraepithelial neoplasia grade 2 was not associated with lower 3-year risks for cervical cancer or cervical intraepithelial neoplasia grade 3 or more severe compared with delayed treatment, according to a target trial emulation. Immediate treatment was associated with substantially more potentially unnecessary excisions.
Researchers analyzed electronic health record data from Kaiser Permanente Northern California to emulate a randomized trial among 12,012 patients with a first biopsy-confirmed diagnosis of cervical intraepithelial neoplasia grade 2 (CIN 2) between 2017 and 2023. Immediate treatment was defined as excision within 6 months without interim surveillance. Delayed treatment consisted of continued surveillance with screening or colposcopy, regardless of whether excision was later performed, or excision at least 6 months following diagnosis.
The primary outcomes were 3-year risks for invasive cervical cancer and cervical intraepithelial neoplasia grade 3 or more severe (CIN 3+). Researchers also evaluated excision outcomes, including potentially unnecessary excisions, defined as excisions yielding less severe disease than CIN 2 without concurrent high-grade cytology.
The estimated 3-year risk for cervical cancer was 0.39% with immediate treatment and 0.43% with delayed treatment. The estimated 3-year risk for CIN 3+ was 9% and 10%, respectively. Researchers reported no appreciable differences in either outcome during the 3-year follow-up.
The clearest difference between strategies was seen in excision outcomes. Among patients who underwent immediate treatment, 36% had excision specimens showing less severe disease than CIN 2. In the delayed-treatment group, the estimated 3-year probability of a potentially unnecessary excision was 8%.
Subgroup analyses suggested that antecedent screening results may help guide risk stratification. Patients with human papillomavirus (HPV) types 16 or 18 positivity and/or high-grade cytology prior to CIN 2 diagnosis had higher risks for CIN 3+ regardless of management strategy. Among patients with lower-risk antecedent findings—defined as positivity for other high-risk HPV types and normal or low-grade cytology—immediate treatment was associated with a substantially higher probability of potentially unnecessary excision. In this subgroup, the estimated probability of a potentially unnecessary excision was 45% with immediate treatment and 9% with delayed treatment.
The researchers noted several limitations. Because the study was observational rather than randomized, residual confounding from unmeasured factors may have influenced treatment selection and outcomes. Cancer outcomes were uncommon, limiting precision, and follow-up was limited to 3 years. The analysis was also conducted within a single health system.
The findings suggest that delayed treatment may be an option for selected patients with CIN 2, particularly those with lower-risk antecedent screening results, while avoiding some excisions that may not yield clinically meaningful disease. However, the study was not designed to establish equivalence between management strategies over longer follow-up.
“Delaying treatment substantially reduces unnecessary excision without an appreciably higher risk for invasive cervical cancer or CIN 3+ for 3 years,” wrote lead study author Li C. Cheung, PhD, of the National Cancer Institute, and colleagues.
Disclosures: The study was supported by the Intramural Research Program of the National Cancer Institute. The researchers reported that disclosure forms are available with the article online.
Source: Annals of Internal Medicine
