ABSTRACT
Objective:To evaluate the value of p16 INK4a detected by p16 INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods:Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16 INK4a technology, among them, 902 cases were offered p16 INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16 INK4a staining. Participants with complete LCT examination, HR-HPV test, p16 INK4a staining and histopathological examination results were included in this study. The performance of p16 INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) +] were analyzed. Results:(1) One-thousand and ninety-seven cases with complete data of p16 INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ) + and 34 cases of HSIL (CIN Ⅲ) + were detected. The positive rate of p16 INK4a in HSIL (CIN Ⅱ) + was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P<0.01). (2) p16 INK4a as primary screening for HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P>0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P<0.05). p16 INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P>0.05). (3) The specificity of LCT adjunctive p16 INK4a for detecting HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + were higher than that of LCT alone or adjunctive HR-HPV ( P<0.01), while the sensitivity were similar ( P>0.05). (4) p16 INK4a staining as secondary screening: p16 INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P<0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P>0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16 INK4a was equally sensitive (88.2% vs 94.1%; P=0.500) and more specific (88.3% vs 83.0%; P<0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P=0.005). Conclusions:For primary screening, p16 INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16 INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16 INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.
ABSTRACT
Objective:Evaluation of the clinical value of the BioPerfectus multiplex real time (BMRT)-HPV for cervical cancer screening.Methods:Physician-collected specimens of 1 495 women who were positive of Cobas 4800 HPV (Cobas-HPV), HPV genotyping based on SEQ uencing (SEQ-HPV), and (or) cytology ≥low grade squamous intraepithelial lesion (LSIL) in the primary screening of Chinese Multiple-center Screening Trial (CHIMUST), and 2 990 women selected from those who were negative of primary screening in the same project through nested control randomization with age-matching were tested for BMRT-HPV, which reported type-specific viral loads/10 000 cells in each specimen. With comparing to Cobas-HPV results and taking cervical histopathological diagnosis as the endpoint, the concordance of high-risk (HR)-HPV subtypes among the three assays was explored ,and the sensitivity and specificity of BMRT-HPV for cervical cancer screening were evaluated.Results:(1) The overall agreenment of HR-HPV subtypes between BMRT-HPV and Cobas-HPV, or SEQ-HPV test sample was 94.8%, 94.4%, with Kappa values 0.827, 0.814. (2) The sensitivity and specificity for cervical intraepithelial neoplasia (CIN) Ⅱ + of BMRT-HPV, Cobas-HPV and SEQ-HPV were 92.62%, 94.26%, 93.44% and 84.67%, 83.25%, 82.76%, respectively. There were no significant difference in sensitivity among the three HPV assays (all P>0.05), but the specificity of BMRT-HPV for CIN Ⅱ + was higher than those of Cobas-HPV and SEQ-HPV ( P<0.01). The sensitivity for CIN Ⅲ + of three HPV assays were all 100.00%, and the specificity for CIN Ⅲ + of BMRT-HPV was higher than those of Cobas-HPV and SEQ-HPV (83.40% vs 81.95%, 83.40% vs 81.50%; P<0.01). The number of pathological examinations of colposcopy for cervical biopsy detected in 1 case of CIN Ⅱ + or CIN Ⅲ + in BMRT-HPV was less than those in Cobas-HPV and SEQ-HPV ( P<0.01). When using HPV 16/18 + cytology ≥atypical squamous cell of undetermined signification (ASCUS) to triage HPV positive women among three assays, there was no different in the sensitivities of detecting CIN Ⅱ + and CIN Ⅲ + ( P>0.05). The specificity BMRT-HPV was slightly higher than those in Cobas-HPV or SEQ-HPV (all P<0.05), and the colposcopy referral rate was lower than those in Cobas-HPV and SEQ-HPV (all P<0.05). Conclusions:BMRT-HPV is as sensitive as Cobas-HPV or SEQ-HPV for primary cervical cancer screening, and has higher specificity. Therefore it could be used as a primary screening method for cervical cancer, which is worthy of clinical application.