Predictive Contribution of p16 Beyond HPV Genotype in the Histopathologic Detection of CIN2+ Lesions: A Real-World Cervical Biopsy Cohort Study
Diagnostics, cilt.16, sa.17, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 16 Sayı: 17
- Basım Tarihi: 2026
- Doi Numarası: 10.3390/diagnostics16172784
- Dergi Adı: Diagnostics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Anahtar Kelimeler: cervical intraepithelial neoplasia, CIN2+, human papillomavirus, HPV genotype, p16INK4a, Ki-67, cervical biopsy, risk stratification, immunohistochemistry, predictive modeling
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Background: HPV genotype-based stratification estimates cervical disease risk but does not directly measure cellular transformation. We assessed whether p16 and Ki-67 improve prediction of CIN2+ beyond HPV genotype and age in a biopsy-confirmed referral cohort. Methods: This retrospective study included 531 high-risk HPV-positive women evaluated between December 2023 and January 2026 who had either margin-negative excisional histopathology or completed 12-month surveillance after conservative management. HPV genotypes were grouped as HPV16, HPV18, or other high-risk types. Independent associations were examined using prespecified multivariable logistic models; discrimination, calibration, 2000-resample bootstrap validation, and a uniform index-biopsy-reference sensitivity analysis were evaluated. Results: CIN2+ was confirmed in 191/531 women (36.0%). HPV16 positivity (adjusted odds ratio [aOR] 1.72, 95% confidence interval [CI] 1.15–2.57), age (aOR 1.027 per year, 95% CI 1.011–1.043), and p16 positivity (aOR 2.97, 95% CI 1.81–4.89) independently predicted CIN2+, whereas Ki-67 did not (aOR 1.74, 95% CI 0.90–3.35; p = 0.098). Adding p16 to age and genotype increased the AUC from 0.608 to 0.704 (ΔAUC 0.097, bootstrap 95% CI 0.057–0.138); Ki-67 increased it only to 0.707 (ΔAUC 0.003, 95% CI −0.002 to 0.015). Optimism-corrected AUCs were 0.599, 0.696, and 0.697, respectively. The uniform biopsy-reference analysis produced the same pattern. Conclusions: p16 provides reproducible incremental risk information beyond age and HPV genotype in biopsy-confirmed cervical disease, whereas Ki-67 adds little once p16 is known. Neither biomarker should replace histopathology-guided management.