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Expression of p16 super(INK4A) in cervical precancerous lesions is unlikely to be preventable by human papillomavirus vaccines

BACKGROUND Whether higher grade cervical intraepithelial neoplasia (CIN grade 2 or greater [CIN greater than or equal to 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...

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Bibliographic Details
Published in:Cancer 2016-12, Vol.122 (23), p.3615-3623
Main Authors: Badiga, Suguna, Chambers, Michelle M, Huh, Warner, Eltoum, Isam-Eldin A, Piyathilake, Chandrika J
Format: Article
Language:English
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Summary:BACKGROUND Whether higher grade cervical intraepithelial neoplasia (CIN grade 2 or greater [CIN greater than or equal to 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 p16 super(INK4A) as 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. METHODS 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 p16 super(INK4A) and the risk of being diagnosed with CIN 2 or CIN 3. Differences in the proportion of CIN greater than or equal to 2 lesions that were positive for p16 super(INK4A) expression by vaccine-related or nonvaccine-related HR-HPV genotype were determined using the Pearson chi-square test. RESULTS Specimens that were positive for p16 super(INK4A) expression 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 greater than or equal to 2 lesions that were negative for the bivalent and 9-valent HR-HPV genotypes had similar rates of positive p16 super(INK4A) expression compared with lesions that were positive for those HR-HPV genotypes. CONCLUSIONS 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. copyright 2016 American Cancer Society. The authors investigate whether cervical precancerous lesions that may develop because of high-risk human papillomavirus genotypes that are not included in human papillomavirus vaccines are likely to have similar malignant potential using p16 super(INK4A) as a biomarker. The results demonstrate that such higher grade precancerous lesions have similar malignant potential compared with similar lesions that are preventable by human papillomavi
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.30229