Human papillomavirus messenger RNA assay for cervical cancer screening: the Shenzhen Cervical Cancer Screening Trial I.

INTRODUCTION: Testing for high-risk types of human papillomavirus (HPV) has been consistently more sensitive than cervical cytology for high-grade precancers and cancers of the cervix (cervical intraepithelial neoplasia grade 2 or higher) but less specific. New assays are being developed to improve on the overall accuracy of molecular testing. The Gen-Probe APTIMA HPV assay (AHPV) is a multiplex assay that qualitatively detects 14 HPV types in a single tube. Because the AHPV targets HPV-E6/E7 messenger RNA transcripts, it should theoretically have a greater specificity than HPV assays that detect HPV DNA. The objective of this study was to compare the sensitivity and the specificity of the Gen-Probe AHPV with those of the Qiagen Hybrid Capture 2 assay (HC2) and liquid-based cytologic examination for cervical cancer screening. METHODS: A total of 2098 unscreened or poorly screened women 25 to 59 years of age were recruited in the city of Shenzhen, China. Two cervical specimens were collected: 1 in SurePath liquid for cytologic examination and 1 in PreservCyt for HPV testing by HC2 and the AHPV. The testing was performed by blinded technicians according to the manufacturer's instructions. Women who had atypical squamous cells of undetermined significance or worse cytologic diagnosis and/or were HPV positive by either assay were asked to return for colposcopy and biopsy. RESULTS: Overall, 2095 women had complete data. Overall, 16.5% of the women were positive on HC2, 10.1% were positive on the AHPV, 5.45% had atypical squamous cells of undetermined significance or greater on cytologic examination, and 1.4% had histologically confirmed cervical disease: cervical intraepithelial neoplasia grade 2 or higher. The sensitivity values of liquid-based cytologic examination, HC2, and the AHPV were 66.7%, 88.9%, and 100%, respectively. The specificity values were 95.5%, 84.5%, and 91.2%, respectively. The AHPV was significantly more accurate by receiver operating characteristic curve comparison (P = 0.005). CONCLUSIONS: The low false-positive rate (high specificity) and the high sensitivity of the AHPV makes this assay suitable for use as a primary assay for detecting cervical disease in a screening setting.

Prevalence of high-risk human papillomavirus and incidence of cervical intraepithelial neoplasia in female populations in Shenzhen, Guangdong Province / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the prevalence of high-risk human papillomavirus (HPV) and incidence of cervical intraepithelial neoplasia (CIN) in female populations in Shenzhen, Guangdong Province, China.</p><p><b>METHODS</b>Totally 1137 women aged 15-59 from Shahe Community, Nanshan District, Shenzhen were investigated for cervical cancer during an population-based epidemiological screening from November 2004 to December 2004. Visual inspection with acetic acid (VIA), colposcopy, liquid-based cytology test (LCT), and hybrid capture 2 (HC-) were performed to detect the high-risk HPV types in cervical secretions. Biopsy under colposcope was performed in women who were HPV-positive with LCT >or= atypical squamous cells of undetermined sign (ASCUS) or HPV-negative with LCT >or= low grade squamous intraepithelial lesion (LSIL), with the pathological results as the golden standards.</p><p><b>RESULTS</b>The detection rate of high-risk HPV-DNA was 14.0%. HPV detection rates in 15-24, 25-29, 30-34, 35-39, 40-44, 45-49, and 50-59 age groups were 15.5%, 17.7%, 12.6%, 8.8%, 10.2%, 15.3%, and 21.0%, respectively (P < 0.05). HPV detection rates in 25-29 years group and 50-59 years group were significantly higher than those in other groups (P < 0.05) and 35-39 group had the lowest detection rate. The curve of HPV infection rates in all groups was 'V' type. The overall incidence of CIN was 4.4%. The incidences of CIN , CIN , and CIN were 3.2%, 1.0%, and 0.3%, respectively, in which the incidence of CIN was significantly higher than those of CIN and . HPV detection rates increased with cervical lesion grades, which in >or=CIN groups and normal group were 100.0% and 8.3%, respectively. No cervical cancer was identified in this research. The sensitivities of VIA, colposcopy, LCT, and HC-II for high-risk HPV screening were 35.7%, 50.0%, 92.9%,and 100%, respectively, in detecting high-grade squamous intraepithelial lesion (HSIL), the specificities of these four methods were 96.0%, 87.2%, 88.4%, and 86.9%, respectively. Satisfactory negative predictive values were obtained for all methods.</p><p><b>CONCLUSIONS</b>HPV infection is the main risk factor for CIN. Cervical cancer among female populations in Shenzhen is still in early stages. Prevention of HPV infection and treatment of CIN are key for the prevention of cervical cancer.</p>

Clinical application of telomerase RNA component gene amplification assay in cervical lesions / 中华妇产科杂志

Objective To investigate the significance of genomic amplification of the telomerase RNA component (TERC) gene to serve as a genetic biomarker in the screening of cervicallesions.Methods A total of 715 cases were recruited,with liquid-based cytology diagnosis as normal (n=347),atypical squamous cells of undetermined significance (ASCUS,n=180),atypical squamous cells cannot exclude a high-grade lesion (ASC-H,n=13),low-grade squamous intraepithelial lesions (LSIL,n=115),high-grade squamous intraepithelial lesions(HSIL,n=59)and atypical glandular cells(AGC,n=1).The remaining cervical cells in the cytological preserving fluid were analyzed using a two-color fluorescence in situ hybridization (FISH) probe targeted to chromosome 3q26 containing TERC gene.The TERC gene findings were compared to the cytological and histological detected results,as well as high-risk human papillomavirus (HPV) detected results.Results Genomic amplification of TERC gene was found in 5.8% of normal specimens,22.2% of ASCUS.30.8% of ASC-H,27.8% of LSIL,86.4% of HSIL and 1/1 of AGC.The positive rate was significantly lower in normal,ASCUS,ASC-H and ISIL.compared with HSIL(all P<0.01).Significantly more cells with genomic amplification of TERC gene were found in cervical intraepithelial lesion(CIN) Ⅱ-Ⅲ than CIN Ⅰ (77.8% vs.9.3%),as well as invasive cervical cancer (96.7% vs.9.3%).both P < 0.01.The rate of TERC gene amplification was higher in HPV positive patients (33.5%) than in HPV negative patients(5.2%,P<0.01).The sensitivity of TERC gene amplification was significantly higher than that of cytological screening (81.88% vs.36.96%,P<0.01) in the differentiation of CIN Ⅱ or higher and CIN Ⅰ or lower diseases,its specificity Was hisher than high-risk HPV test (93.32% vs.33.93%,P<0.01) and positive prediction value (81.29%) was similar with cytological method (86.44%,P>0.05);but its negative prediction value (93.56%) was lower than HPV test (97.06%,P<0.05).Conclusions The positive rates of TERC gene amplification increased as cervical diseases worsened.TERC gene amplification is related to HPV infection.The gain of chromosome 3q26 in cytological specimens is an effective molecular genetic biomarker in screening of CIN Ⅱ or higher and invasive cervical cancer.

Amplification and clinical significance of hTERC gene in the cervical exfoliated cells from natural population in Shenzhen / 中华流行病学杂志

the severity of cytological and histological grade. The evidence of hTERC, with or without amplification, might serve as a prognostic indicator to measure the grade of lesion.

Distribution of human papillomavirus types in Shenzhen women / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the status of genital infection as well as distribution of types of human papillomavirus (HPV) in women in Shenzhen and provide population data for the future vaccine intervention on cervical cancer.</p><p><b>METHODS</b>Women with age between 15 and 59 years were selected in cluster stratified sampling from Huaqiaocheng community, Nanshan district, Shenzhen and received a population-based cervical cancer screening. After consent, every woman was interviewed by using questionnaire and tested by liquid-based cytology and HPV DNA (hybrid capture 2 and gene chips typing) separately.</p><p><b>RESULTS</b>Totally 1 137 women were screened. The rate of high risk HPV of hybrid capture 2 test (14. 0% ) was higher than gene chips typing test (9. 8%) (chi(2) = 27. 198, P < 0. 001) ; the consistency of the two tests was acceptable ( kappa = 0. 498, P < 0. 001). The rates of low risk HPV types and other types of gene chips typing test in this population were 1. 9% and 0. 2% respectively. The percentages of HPV 16, 18 and 58 in HPV positive women were 29. 7% , 18. 9% and 18. 9%. The rates of different age group of low risk HPV were 1. 4% (17-34), 1. 7% (35-44) and 3. 2% (45-59) , respectively.</p><p><b>CONCLUSIONS</b>HPV 16, 18, and 58 are the most popular types in the study population. The differences of infection rates of high risk HPV are due primarily to the variation of HPV16 distribution among age-specific population. The chances of being affected by low risk HPV will increase with age.</p>