Progression of Precancerous Cervical Lesion Predicted by p16 Protein Immunohistochemistry in Rajavithi Hospital

Document Type : Research Articles


Department of Obstetrics and Gynecology, Rajavithi Hospital, Bangkok, Thailand.


Objective: To assess the association of p16 immunohistochemical (IHC) staining in cervical squamous intraepithelial
lesions (SIL) and progression of cervical intraepithelial neoplasia (CIN) 1 to CIN2+ or recurrence of CIN2+. Material
and Methods: A retrospective cohort study of women with newly diagnosed SIL from colposcopy-directed biopsy at
Rajavithi Hospital, 2013-2017. Pathologic specimens were reviewed and submitted to p16-IHC staining. Adjusted hazard
ratios (HR) of disease-free interval (DFI) and 95% confidence intervals (CI) were carried out using the Cox proportional
hazard regression model. Results: A total of 187 women was recruited, 91 cases of positive p16-IHC staining and 96
cases of negative staining. With the median follow-up time of 22 months, women with positive p16-IHC had significantly
lower 1-year DFI than those with negative p16-IHC (86.8% vs. 96.6%, p = 0.006). Women with CIN 1 had 22.6% of
positive p16-IHC, while those with CIN2-3 had 86.7%. From multivariate analysis, the positive p16-IHC and age >
35 years were the significant prognostic factors of progression/recurrent CIN2+ (adjusted HR 5.33, 95%CI 1.77-16.01,
p = 0.003; and adjusted HR 5.80, 95%CI 1.34-25.08, p = 0.019, respectively). From subgroup analysis, the positive
p16-IHC was the significant prognostic factor in women with initial CIN1 (HR 5.29, 95%CI 1.18-23.76, p = 0.030), but
was not associated with prognosis in women with initial CIN 2-3 (HR 2.13, 95%CI 0.28-16.38, p = 0.468). Conclusion:
Overexpression of p16 protein has the prognostic significance of SIL. Using p16-IHC may help stratify patients as
low-risk and high-risk groups to progression/recurrence CIN2+.


Main Subjects