title: Expression of p16INK4Ain cervical precancerous lesions that is unlikely to be preventable by human papillomavirus vaccines.
abstract: Whether higher grade cervical intraepithelial neoplasia (CIN grade 2 or greater [CIN ≥ 2]) that develops because of human papillomavirus (HPV) genotypes not included in vaccines may progress to cervical cancer is largely unknown. The objectives of this study were to document expression of the cyclin-dependent kinase inhibitor 2A (p16) tumor-suppressor protein p16INK4Aas a biomarker of cervical carcinogenesis or of malignant potential and to evaluate whether its expression differs between lesions associated with vaccine and nonvaccine high-risk (HR) human papillomavirus (HPV) genotypes.
  
  
  
  The study population consisted of 371 women who had not received HPV vaccines. Women were categorized into vaccine and nonvaccine HR-HPV genotypes and lesions associated with those types. Logistic regression analyses were used to determine the association between positive expression p16INK4Aand the risk of being diagnosed with CIN 2 or CIN 3. Differences in the proportion of CIN ≥2 lesions that were positive for p16INK4Aexpression by vaccine-related or nonvaccine-related HR-HPV genotype were determined using the Pearson chi-square test.
  
  
  
  Specimens that were positive for p16INK4Aexpression were 5.3 and 16.6 times more likely to be diagnosed as CIN 2 and CIN 3 lesions, respectively, compared to CIN 1 lesions. CIN ≥ 2 lesions that were negative for the bivalent and 9-valent HR-HPV genotypes had similar rates of positive p16INK4Aexpression compared with lesions that were positive for those HR-HPV genotypes.
  
  
  
  Lesions that may develop because of HR-HPV genotypes not included in HPV vaccines are likely to have similar malignant potential, suggesting that well developed screening programs combined with nonvaccine-based approaches may be needed to manage the residual risk of developing cervical cancer in the post-HPV vaccination era. Cancer 2016;122:3615-23. © 2016 American Cancer Society.
authors.affiliation: Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Suguna
authors.initials: S
authors.lastname: Badiga
authors.affiliation: Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Chambers
authors.affiliation: Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Warner
authors.initials: W
authors.lastname: Huh
authors.affiliation: Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Isam-Eldin A
authors.initials: IA
authors.lastname: Eltoum
authors.affiliation: Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Chandrika J
authors.initials: CJ
authors.lastname: Piyathilake
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D027383:Papillomaviridae / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000276:immunology*; D011230:Precancerous Conditions / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000276:immunology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D053918:Papillomavirus Vaccines
keywords: cervical intraepithelial neoplasia (CIN); cervix; cyclin-dependent kinase inhibitor 2A (p16); human papillomavirus (HPV); vaccine