Local Treatment Choice for Cervical Intraepithelial Neoplasia and Stage IA1 Cervical Cancer Appears to Influence Efficacy, Risk of Preterm Birth

In a population of patients with cervical intraepithelial neoplasia and stage IA1 cervical cancer, certain local treatments, such as radical excision and ablation, were associated with treatment outcomes and risk of preterm birth.

Radical excision techniques were associated with a reduction in treatment failure but an increased risk of subsequent preterm birth, while ablative strategies were associated with fewer preterm births but higher treatment failure among patients with cervical intraepithelial neoplasia (CIN) and stage IA1 cervical cancer, according to findings from a systemic review and meta-analysis published in Lancet Oncology.

Investigators noted that compared with large loop excision of the transformation zone (LLETZ), excisional methods such as laser conization (odds ratio [OR], 0.59; 95% CI, 0.44-0.79) and cold knife conization (CKC; OR, 0.63; 95% CI, 0.50-0.81) resulted in a decreased risk of treatment failure. However, strategies such as laser ablation (OR, 1.69; 95% CI, 1.27-2.24) and cryotherapy (OR, 1.84; 95% CI, 1.33-2.56) were associated with an increased risk of failure vs LLETZ. Although based on 2 smaller studies, investigators did not note any differences in efficacy between those treated with cold coagulation and LLETZ (OR, 1.09; 95% CI, 0.68-1.74).

“To our knowledge, this is the first network meta-analysis to explore the comparative effectiveness and reproductive morbidity for different treatments for CIN. Our findings suggest that more aggressive local CIN treatments are associated with a reduced risk of treatment failure but an increased risk of preterm birth in subsequent pregnancies. We identified previously unknown differences and reported lower rates of treatment failure among more radical excisional treatment techniques (CKC or laser conisation) than with LLETZ. Our results for treatment failure were consistent in secondary analyses using various cutoffs for definition of treatment failure and for high-risk HPV positivity rates at 6 months,” the investigators wrote.

All aforementioned excisional strategies including CKC (OR, 2.27; 95% CI, 2.27; 95% CI, 1.70-3.02), laser conization (OR, 1.77; 95% CI, 1.29-2.43), and LLETZ (OR, 1.37; 95% CI, 1.16-1.62) were associated with an increased risk of preterm birth vs the untreated colposcopy cohort. However, no differences were observed among those treated with laser ablation (OR, 1.05; 95% CI, 0.78-1.41), cryotherapy (OR, 1.01; 95% CI, 0.35-2.92), and cold coagulation (OR, 0.67; 95% CI, 0.02-29.15) compared with the untreated colposcopy cohort.

To conduct the systemic review and meta-analysis, investigators searched databases for publications that reported oncologic or reproductive outcomes following CIN treatment. They included patients with CIN, stage IA1 cervical cancer, or glandular intraepithelial neoplasia who were treated using excisional or ablative strategies in their analysis.

A total of 7880 potential citations were identified for treatment failure, 81 of which met the analysis’ eligibility criteria. Moreover, 4107 potential citations were identified for preterm birth, with 92 being used in the analysis. A total of 19,240 patients from 71 studies were assessed for treatment failure and 68,817 from 29 studies were assessed for preterm birth. Investigators noted that most nonrandomized studies and some randomized studies were at risk for bias.

The median age in the treatment failure assessment was 33 years with a median duration to diagnosis treatment failure of 15 months. The median age at pregnancy in the other cohort was 30 years and the median interval could not be determined. Across both groups, most patients had been treated for high-grade disease, with a low rate of patients treated for adenocarcinoma in situ or stage IA1 cervical cancer.

Findings from a subgroup analysis indicated that among patients with endocervical lesions, patients who received LLETZ has an increased rate of treatment failure vs CKC or laser conization, regardless of technique. Another subgroup analysis found that the odds of treatment failure following laser ablation and cryotherapy compared with LLETZ resulted in increased risk of treatment failure with lesion grade, the highest of which was CIN3. However, laser ablation and cryotherapy continued to have the higher risk of treatment failure vs LLETZ across prespecified subgroups among patients younger than 33 years.


Athanasiou A, Veroniki AA, Efthimiou O, et al. Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis. Lancet. 2022;23(8):1097-1108. doi:10.1016/S1470-2045(22)00334-5