Diagnostic Accuracy Of Hybrid Capture 2 And Thinprep Cytologic Test And Their Co-testing In Different Age Groups In Diagnosis Of Cervical Intraepithelial Neoplasia

BackgroundCervical carcinoma ranks second among the common cancers in women worldwide. Cervical intraepithelial neoplasia (CIN) is an important stage in the prevention of cervical cancer which reflects the continuous process in the occurrence and development of cervical cancer. Persistent infection with high-risk human papillomavirus (HPV) is the main cause of CIN and virtually all cervical cancer. High rates of spontaneous regression have been reported for CIN1 lesions that remain untreated, and thus progression of CIN1 to CIN2 or worse is rarely observed. Under current clinical guidelines recommended by WHO, women with CIN1 are to be monitored while those with CIN2 or worse (CIN2+) lesions are usually referred for immediate therapy. Cervical screening is the most important means to prevent cervical cancer and significantly reduced the morbidity and mortality. The most important screening techniques are cervical cytology which represented by "Thinprep Cytologic Test" (TCT) and HPV test which represented by "Hybrid Capture 2 test" (HC2). The primary indications for HPV testing currently in the world include the triage in women with minor cervical cytologic abnormalities (Atypical Squamous Cells of Undetermined Signification (ASCUS, for short) and Low-grade Squamous Intraepithelial Lesion (LSIL, for short)) and co-testing with cytology test. But the high incidence of HPV infection in women with minor cervical cytologic abnormalities makes the triage value limited. Several studies have explored the possibility of triage of HPV-positive women at higher thresholds, but controversy still remains. The morbidity of cervical cancer and the risk factors, such as the incidence rate of HPV infection and cytology results varies with age. So that, just as the 2012 American guidelines of screening for cervical cancer, different screening strategies should be applied to different ages.ObjectiveTo study the diagnostic accuracy of HC2 and TCT and their co-testing in different age groups in diagnosis of CIN.MethodsThe retrospective study reviewed medical records of patients who referred to the Peking Union Medical College Hospital for colposcopy from October 2012 to November 2014. Women to whom the results of TCT and HC2 were available in the past 3 months before the colposcopy were included. The exclusion criteria was as follows:(1) Women with a history of prior CIN treatment (LEEP or CKC) or hysterectomy; (2) Women had ablative treatment in the past 5 years; (3) Women in pregnant. A total of 1168 women were included.The patients were assigned to six groups (-30,31-35,36-40,41-45,46-50,51-) based on their age. Receiver operating characteristic (ROC) curve analysis was used to test the diagnosis potential of the HC2 and to obtain the best cutoff value. The AUC (area under the ROC curve) were performed to evaluate the prediction effectiveness. The maximum Youden index was used to evaluate the diagnostic accuracy. The statistics was performed with MedCalc(?) version 11, Graphpad Prism version 5, SPSS 21.0 and Microsoft Excel 13.Results(1) The AUC was 0.567(95%CI:0.538-0.586) without triage of any cytology and the AUC was higher in women age 51 or more than that in women age 50 or less (P<0.05).(2) The best cut-off value obtained by the ROC analysis increased with age, and it was always higher than 1 RLU/CO. The best cut-off value in women aged 30 or less,31-50 and 50 or more were 5.33RLU/CO,118.16 RLU/CO and 420.16 RLU/CO respectively.(3) For triage of ASCUS, no significant difference was observed among different age groups(P>0.05). For triage of LSIL, the results were similar to that in women without triage of any cytology.(4) No significant difference of the Youden index was observed among different age groups at the cut-off of ASCUS (P<0.05). But the Youden index increased along with age at the cut-off of LSIL. The Youden index in women aged 30 or less,31-50 and 50 or more were significant statistical different (P<0.05).(5) The Youden index of TCT in HPV positive women increased with age (P<0.05). Except for women aged 30 and younger, the Youden index was higher when HC2 was used as the first-line primary cervical screening (P<0.05).(6) The Youden index of combined testing was not significant differennt among different age groups at the cut-ff of ASCUS(P>0.05), but was higher in women aged 50 or more than less (P<0.05) at the cut-ff of LSIL.(7) The Youden index of combined testing in diagnosis of CIN was higher than TCT at the cut-off of ASCUS (P<0.05). A higher thresholds at 100 RLU/CO results in further increase of the Youden index at 1 RLU/CO (P<0.05). There was no significant difference between combined testing and TCT at the cut-off of LSIL (P>0.05).Conclusions(1) The diagnostic accuracy in women older than 50 was higher than that in women 50 or younger when primary screen with HC2 or test with HC2 or TCT alone. But no significant difference was observed when primary screen with TCT or co-test.(2) A higher thresholds could improve the diagnostic accuracy of HC2. (3) Except for women aged 30 and younger, the diagnostic accuracy was higher when HC2 was used as the first-line primary cervical screening.(4) The diagnostic accuracy of combined testing with HC2 and TCT in diagnosis of CIN was higher than TCT alone.