OBJECTIVE: The current system of Pap smear screening and management of abnormal cytology has resulted in a marked reduction in invasive cervical cancer. Many women, however, are not found to have significant precursor lesions. This is due to the poor specificity of high-risk human papillomavirus (HPV) triage. More specific cervical cancer biomarkers may be more effective triage tools than hr-HPV. We evaluated whether a dual stain for p16 and Ki-67 might improve the triage of abnormal Pap smears. MATERIALS AND METHODS: p16/Ki-67 immunostaining was performed on additional slides prepared from 515 women with abnormal Pap smears (301 atypical squamous cells of undetermined significance [ASCUS], 169 low-grade squamous intraepithelial lesion [LSIL], 29 atypical squamous cells-cannot exclude high-grade lesion [ASC-H], 16 high-grade squamous intraepithelial lesion [HSIL]). High-risk HPV typing was performed on all cases. Immunostaining and hr-HPV were compared in relation to their diagnostic accuracy for the detection of biopsy-proven cervical intraepithelial neoplasia (CIN) 2/3. A cost analysis comparing hr-HPV versus immunostaining as the initial triage tool used for abnormal Pap smears was also performed. RESULTS: High-risk HPV was positive in 127 (42.2%) ASCUS, 129 (76.3%) LSIL, 20 (69.0%) ASC-H, and 15 (93.8%) HSIL. p16/Ki-67 was positive in 54 (17.9%) ASCUS, 73 (43.2%) LSIL, 19 (65.5%) ASC-H, and 15 (93.8%) HSIL. For detection of CIN 2/3, sensitivity/specificity of hr-HPV and p16/Ki-67 was 89.29%/14.94% and 96.43%/60.92%, respectively. Overall, diagnostic accuracy was statistically significantly higher for p16/Ki-67 compared with hr-HPV. Compared to HPV, immunostain triage could have generated approximately $46,000 savings in the study population. CONCLUSIONS: The triage of abnormal Pap smears by p16/Ki-67 immunostaining shows comparable sensitivity, improved specificity, and significantly improved diagnostic performance when compared to hr-HPV. Immunostaining is of value in triaging LSIL and ASC-H Pap smears in addition to ASCUS. The widespread utilization of biomarker triage could result in significant health care cost savings without compromising the detection of significant cervical cancer precursors.
OBJECTIVE: The current system of Pap smear screening and management of abnormal cytology has resulted in a marked reduction in invasive cervical cancer. Many women, however, are not found to have significant precursor lesions. This is due to the poor specificity of high-risk human papillomavirus (HPV) triage. More specific cervical cancer biomarkers may be more effective triage tools than hr-HPV. We evaluated whether a dual stain for p16 and Ki-67 might improve the triage of abnormal Pap smears. MATERIALS AND METHODS:p16/Ki-67 immunostaining was performed on additional slides prepared from 515 women with abnormal Pap smears (301 atypical squamous cells of undetermined significance [ASCUS], 169 low-grade squamous intraepithelial lesion [LSIL], 29 atypical squamous cells-cannot exclude high-grade lesion [ASC-H], 16 high-grade squamous intraepithelial lesion [HSIL]). High-risk HPV typing was performed on all cases. Immunostaining and hr-HPV were compared in relation to their diagnostic accuracy for the detection of biopsy-proven cervical intraepithelial neoplasia (CIN) 2/3. A cost analysis comparing hr-HPV versus immunostaining as the initial triage tool used for abnormal Pap smears was also performed. RESULTS: High-risk HPV was positive in 127 (42.2%) ASCUS, 129 (76.3%) LSIL, 20 (69.0%) ASC-H, and 15 (93.8%) HSIL. p16/Ki-67 was positive in 54 (17.9%) ASCUS, 73 (43.2%) LSIL, 19 (65.5%) ASC-H, and 15 (93.8%) HSIL. For detection of CIN 2/3, sensitivity/specificity of hr-HPV and p16/Ki-67 was 89.29%/14.94% and 96.43%/60.92%, respectively. Overall, diagnostic accuracy was statistically significantly higher for p16/Ki-67 compared with hr-HPV. Compared to HPV, immunostain triage could have generated approximately $46,000 savings in the study population. CONCLUSIONS: The triage of abnormal Pap smears by p16/Ki-67 immunostaining shows comparable sensitivity, improved specificity, and significantly improved diagnostic performance when compared to hr-HPV. Immunostaining is of value in triaging LSIL and ASC-H Pap smears in addition to ASCUS. The widespread utilization of biomarker triage could result in significant health care cost savings without compromising the detection of significant cervical cancer precursors.
Authors: Renée Mf Ebisch; Judith van der Horst; Meyke Hermsen; L Lucia Rijstenberg; Judith Em Vedder; Johan Bulten; Remko P Bosgraaf; Viola Mj Verhoef; Daniëlle Am Heideman; Peter Jf Snijders; Chris Jlm Meijer; Folkert J van Kemenade; Leon Fag Massuger; Willem Jg Melchers; Ruud Lm Bekkers; Albert G Siebers Journal: Mod Pathol Date: 2017-03-17 Impact factor: 7.842
Authors: Yung Taek Ouh; Ji Jeong Park; Minjoo Kang; Miseon Kim; Jae Yun Song; So Jin Shin; Seung Hyuk Shim; Heon Jong Yoo; Maria Lee; Sung Jong Lee; Whan Shin; Gun Oh Chong; Min Chul Choi; Chel Hun Choi; Kyung Jin Min Journal: J Korean Med Sci Date: 2021-06-21 Impact factor: 2.153
Authors: Abraham Pouliakis; Efrossyni Karakitsou; Charalampos Chrelias; Asimakis Pappas; Ioannis Panayiotides; George Valasoulis; Maria Kyrgiou; Evangelos Paraskevaidis; Petros Karakitsos Journal: Biomed Res Int Date: 2015-08-03 Impact factor: 3.411