Background/Objectives: When the squamocolumnar junction is not fully visible (type 3 transformation zone), colposcopy-directed biopsy may under-sample endocervical disease. Endocervical curettage (ECC) is recommended in selected settings, but its incremental diagnostic yield in this setting, and whether this yield is concentrated in women with HPV16/18, remains clinically debated. Methods: We performed a retrospective cohort study of women referred to colposcopy because of HPV16/18 positivity regardless of cytology, persistent non-16/18 high-risk HPV positivity, and non-16/18 high-risk HPV positivity with abnormal cytology. Persistent non-16/18 high-risk HPV positivity was defined as repeated positivity on two tests performed at least 6 months apart. Eligible women had type 3 transformation zone documented and underwent paired ectocervical biopsy plus ECC at the same visit; biopsy was obtained in all women, including targeted sampling of the most abnormal ectocervical area when no discrete lesion was evident. Women were stratified by HPV genotype into HPV16/18 and non-16/18 high-risk HPV groups. The primary outcome was index high-grade cervical lesion, defined histologically as CIN2, CIN3, or carcinoma in situ; invasive cervical cancer was excluded. The added diagnostic yield of ECC was defined as ECC-only CIN2+, that is, CIN2+ detected on ECC when biopsy was <CIN2. Results: The cohort included 690 women (HPV16/18: 310; non-16/18 high-risk HPV: 380). Baseline cytology was negative for intraepithelial lesion or malignancy in 116 individuals (16.8%), ASC-US in 155 (22.5%), LSIL in 205 (29.7%), and ASC-H/HSIL in 214 (31.0%). On index composite histology, 122/690 (17.7%) had CIN2, 198/690 (28.7%) had CIN3, and 11/690 (1.6%) had carcinoma in situ. ECC identified CIN2+ not detected by biopsy in 19/690 (2.8%) cases, representing 19/331 (5.7%) of all CIN2+ diagnoses. ECC-only CIN2+ was more frequent in HPV16/18 than non-16/18 high-risk HPV (4.5% vs. 1.3%, p = 0.017). In multivariable analysis, HPV16/18 was associated with increased odds of ECC-only CIN2+ (aOR 3.22, 95% CI 1.10–9.44). No invasive cervical cancers were included in the analytic cohort. Conclusions: In type 3 transformation zone colposcopy, ECC adds a modest incremental yield for CIN2+ detection, with higher yield in HPV16/18-positive women. These findings support a risk-weighted approach to ECC rather than universal routine sampling.

Background/Objectives: Cervical cancer prevention relies on cytology, high-risk human papillomavirus (HR-HPV) testing, and histological confirmation, but these modalities may disagree. We quantified test concordance and determinants of CIN2+ in a specialized gynecologic referral cohort with very low HPV vaccination coverage. Methods: We retrospectively analyzed 172 women evaluated for suspected or established cervical pathology between 2022 and 2024. Of these, 160 had a definitive HPV result and 130 had histology; histology-based performance analyses used complete cases and are conditional on biopsy verification. Cytology was categorized by the Bethesda system, HR-HPV genotypes were recorded, and histology was dichotomized as CIN2+ versus ≤CIN1. Results: Among 160 women with definitive HPV results, 109 (68.1%) were HPV-positive. HPV-positive women were younger (median 33 vs. 43 years, p < 0.001) and, among biopsied women, more frequently had CIN2+ (70.2% vs. 22.2%, p < 0.001). Cyto-histological agreement was fair (65.0%, κ = 0.32). HPV16/18 was strongly associated with CIN2+ (OR 6.85, 95% CI 2.54–18.49). Within histologically verified complete cases, HPV DNA positivity had the highest apparent sensitivity (91.7%), whereas HPV16/18 had the highest PPV (86.0%). Conclusions: Cytology and HR-HPV testing provide complementary information in this referral-enriched cohort. Because disease prevalence was high and biopsy verification was selective, predictive values and apparent diagnostic-performance estimates should not be extrapolated directly to population screening; external validation in primary-screening populations is required.