| Part 1Aim:It is reported that hrHPV infections are closely related to the occurrence of cervical cancer. For the exact prevalence of HPV infections in Nanjing City, we researched the relevant clinical and pathological data of young females who primarily attended to our hospital for cervical cancer screening.Methods:Retrospectively we reviewed and analyzed the clinical and pathological data, including patients' age, HPV subtypes and histopathology of cervical lesions, from 896 young women (18 to 30 years old) who visited the department of Obstetrics and Gynecology clinic in Zhongda Hospital from January 2014 to December 2015. Moreover, we preliminarily investigated the potential correlation between HPV prevalence and cervical precursors.Results:1. Among the enrolled 896 young women,281 were positive with HPV infection (31.36%). Furthermore,85.05% were with infected with hrHPV and 35.23% with lrHPV among these HPV-positive patients. The most prevalent five subtypes of hrHPV were HPV52 (19.00%), HPV16 (18.00%), HPV53 (16.00%), HPV39 (9.00%) and HPV58 (8.00%) and the most common three subtypes of lrHPV were HPV81 (50.00%), HPV6 (21.00%) and HPV11 (13.00%).2. Observing the policy of national guideline, we referred 132 patients to colposcopy and biopsy. Due to their histopathological results,74 cases (52.90%) were included into group of cervical benign lesions (average age was 26.00,19 to 30 years),19 cases (13.60%) into LSIL group (average age was 27.30,21 to 30 years),34 cases (24.30%) into HSIL group (average age of 28.20,18 to 30 years), and the rest 5 (3.50%) cases into CC group (all ages with 30 years old). The average age was significantly different among four groups (P< 0.05).3. The incidence of cervical lesions of HSIL+ in women with HPV infection was 45.68%, significantly higher than those (3.92%) with no HPV infection (P<0.05).Conclusions:1. Totally the prevalence of women with HPV positive was 31.36%, as well as hrHPV positive account for 26.67% in Nanjing City. The most prevalent five subtypes of hrHPV were HPV52 (19.00%), HPV16 (18.00%), HPV53 (16.00%), HPV39 (9.00%) and HPV58 (8.00%). Basically, the results are similar to the epidemic investigations reported by other Chinese authors.2. With aging, young women infected with hrHPV are feasibility to HSIL+ lesions.3. HPV 16 is the most common subtype among young women with HSIL+ in Nanjing City.Part 2Aim:To demonstrate the utility of pl6/Ki-67 dual-staining in cervical cancer screening in young Chinese females, we carried out a prospective observation to compare it with HPV subtype detection and cervical cytology testing.Methods:121 patients who attended to Gynecology clinic for the first-round cervical cancer screening from January 2015 to December 2015 were enrolled into our study. The cases who lack of the data of cervical cytology, HPV subtype detection or pathological grade of colposcopic biopsy were ruled out. The procedure of p16/Ki-67 dual-staining was established on cytological slides. Subsequently, pl6/Ki-67 dual-staining in hrHPV-positive young women were evaluated.Results:Totally 108 patients were included into the final statistical analysis,65 of them had benign cervical lesions,15 cases were included into LSIL group,20 were included into HSIL group and the rest 8 were included into CC group. The rates of hrHPV positive were 47.40%,57.10%,89.50% and 100.00% in these four groups, respectively. The rates of cytology positive were 30.77%,80.00%,90.00% and 100.00%. And the positive rates of pl6/Ki-67 dual-staining were 1.54%,20.00%, 95.00% and 100.00%. In diagnosing cervical HSIL+, there was no siganificant differences among HPV (21-subtype) detection, cytology testing and pl6/Ki-67 dual-staining (P>0.05). Comparing to cytology in triaging hrHPV positive patients, pl6/Ki-67 dual-staining presented better sensitivity and specificity. The efficiency of different combinations of either two methods in detecting cervical lesions of HSIL+ was worked out. The three combinations showed similar sensitivity (96.00%), while the cytology combined p16/Ki-67 dual-staining showed excellent specificity (60.00%), negative predictive value (98.00%) and positive likelihood ratio (2.41).Conclusions:The rate of hrHPV positive or pl6/Ki-67 dual-staining positive was increased with the severity of cervical lesions. Overall, p16/Ki-67 dual staining showed better sensitivity, specificity, PPV, NPV, LR+ and LR- in screening cervical cancer than cytology test and HPV (21-subtype) detection. For triaging young women with hrHPV infection, pl6/Ki-67 dual-staining can improved the detection of HSIL+ and showed better diagnostic efficacy. Therefore, it potentially becomes the alternative screening strategy for cervical cancer and precursor lesions. Furthermore, cytology test combined with p16/Ki-67 dual-staining strategy showed excellent performance in detecting cervical HSIL+ with improved sensitivity and specificity.Part 3Aim:Cervical cancer is the second most common cancer among women worldwide, and the major cause of female tumor morbidity in developing countries. Although routine screening contributes to substantial reductions in cervical cancer morbidity and mortality, the low specificity of HPV detection and sensitivity of cervical cytology necessitates the application of more optimized markers, such as the newly-introduced p16/Ki-67 dual-staining method. Here we reviewed several studies to evaluate the performance of this method in cervical cancer screening.Methods:An electronic database search was performed on PubMed, Web of Science, CNKI and Wanfang Database for studies assessing p16/Ki-67 dual immunostaining in the diagnosis of HGCIN with abnormal cytological morphologies. Two reviewers screened literatures, extracted data and assessed the quality of the included studies independently. Meta-analysis was performed using ReV. Man 5.2 and Meta-DiSc 1.2 software packages.Results:The absolute sensitivity of p16/Ki-67 dual staining for diagnosing HGCIN ranged from 80% to 94%, while the sensitivity of triage method with hrHPV testing ranged from 78% to 96%. The specificity of p16/Ki-67 testing and hrHPV detection for predicting absence of CIN2+ ranged from 39% to 79% and 15% to 44%, respectively. Quantitative meta-analysis showed that the pooled sensitivity of p16/ki-67 dual staining is 0.88 [95%CI (0.86-0.90)], the pooled specificity is 0.58 [95%CI (0.56-0.60)]. For hrHPV testing, the pooled sensitivity and pooled specificity is 0.94 [95%CI (0.93-0.96)] and 0.32 [95%CI (0.29-0.34)], respectively.Conclusions:p16/Ki-67 dual immunostaining had comparable sensitivity and improved specificity in screening HGCIN or CC when compared with hrHPV detection. Further studies may be beneficial to assess the efficacy of this novel biomarker, which can be potentially used as one of the initial screening assays. |
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