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p16INK4a Expression does not predict the outcome of cervical intraepithelial neoplasia grade 2
  1. A. C. Guedes*,
  2. S. M.F. Brenna*,
  3. S. A.S. Coelho,
  4. E. Z. Martinez,
  5. K. J. Syrjänen§ and
  6. L. C. Zeferino
  1. * Department of Gynecology, Leonor Mendes de Barros Maternity Hospital, Health State Secretariat, São Paulo, Brazil;
  2. Department of Pathology, Universidade de São Paulo, São Paulo, Brazil;
  3. Department of Social Medicine, Medical School of Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil;
  4. § Department of Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland; and
  5. Department of Gynecology and Obstetrics, The School of Medical Sciences, Universidade Estadual de Campinas, Campinas, Brazil
  1. Address correspondence and reprint requests to: Sylvia M.F. Brenna, MD, PhD, R Toledo Barbosa, 624 ap11 bloco B, São Paulo, SP 03061-000, Brazil. Email: sylviaacademia{at}


Spontaneous regression of cervical intraepithelial neoplasia grade 2 (CIN2) lesions has been recognized since 1955, but predictors of this are poorly understood. Among the predictive markers studied, p16INK4a has been suggested to be of some value in monitoring the diagnosis of CIN2. In this clinical trial, 90 Brazilian women, diagnosed to CIN2 and high-risk human papillomavirus infection, were randomized into two groups of equal size: 45 women whose lesions were excised and 45 women subjected to prospective follow-up at 3-month intervals at least for 1 year (mean 6.8 months). p16INK4a expression was analyzed in paraffin-embedded sections using immunohistochemical staining. Among the 45 women in the follow-up group, 42% experienced spontaneous regression, 11% showed persistence, 22% progressed to CIN3, and 20% had partial regression to CIN1 or ASCUS (atypical squamous cell undetermined signifiance). p16INK4a expression was detected in 68.9% of the patients. In univariate survival (Cox) analysis, no significant difference in regression was obtained between p16INK4a-negative and -positive CIN2 lesions (adjusted HR = 1.1; 95% CI 0.6–2.0). In conclusion, p16INK4a expression could be useful in the diagnosis of CIN2. However, it failed to predict the outcome of CIN2. Because of its high spontaneous regression rate, follow-up could be considered as a management option of CIN2 in young and compliant women.

  • cervical intraepithelial neoplasia
  • CIN2
  • natural history
  • p16INK4a
  • regression

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