Value of p16^INK4a as a marker of progression/regression in cervical intraepithelial neoplasia grade 1

Objective

The objective of this study was to evaluate the usefulness of p16^INK4a staining to classify cervical intraepithelial neoplasia grade 1 according to its progression/regression risk.

Study Design

Patients with a histologic diagnosis of cervical intraepithelial neoplasia grade 1 were prospectively recruited (n = 138). Simultaneous detection of high-risk human papillomaviruses and p16^INK4a evaluation were performed. Follow-up was conducted every 6 months by cytology and colposcopy and annually by high-risk human papillomavirus testing, for at least 12 months (mean, 29.0). Progression was defined as a histologic diagnosis of cervical intraepithelial neoplasia grades 2-3, regression as a negative cytology and high-risk human papillomaviruses, and persistence as a cytologic result of low-grade squamous intraepithelial lesions and/or a positive test for high-risk human papillomaviruses.

Results

Progression was observed in 14 women (10.1%), 66 (47.6%) regressed, and 58 (42.0%) had a persistent disease. p16^INK4a was positive in 77 (55.8%) initial biopsy specimens. Progression to cervical intraepithelial neoplasia grades 2-3 was identified in 14 of 77 (18.2%) women with positive and none of 61 (0.00%) women with negative p16^INK4a immunostaining (P < .001).

Conclusion

p16^INK4a negative cervical intraepithelial neoplasia grade 1 lesions rarely progress and may benefit from a less intensive follow-up.

Key words: cervical intraepithelial neoplasia, CIN1, follow-up, human papillomavirus, immunohistochemistry, p16^INK4a, progression, regression