Objective To study the relationship between cell proliferation and apoptosis in cervical carcinoma and its clinical significance. Methods The cell proliferation and apoptosis of cervical epithelial cells in archival f...Objective To study the relationship between cell proliferation and apoptosis in cervical carcinoma and its clinical significance. Methods The cell proliferation and apoptosis of cervical epithelial cells in archival formalin-fixed, paraffin-embedded tissue sections of normal cervix, cervical intraepithelial neoplasms (GIN) and cervical squamous carcinoma were tested by using immunohistochemistry assay and DNA nick end-labeling technigue. The proliferation index (PI) and apoptosis index (AI) were calculated and their correlation with clinical and pathological data was analyzed.Results PI was gradually increased, but the AI and AI/PI ratio decreased from normal cervical epithelium, GIN to cervical carcinoma. There was no significant relationship among cell proliferation, apoptosis, clinical stages and pathological grades. High AI was always associated with a poor prognosis of the patients.Conclusion Cell proliferation and apoptosis allow to distinguish among normal epithelium, GIN and cervical carcinoma and are useful for the assessment of the malignant potential of tumor tissues.展开更多
Persistent infection wit h high-risk types of human papillomavirus(HPV) is known to cause cervical cancer;however,additional genetic and epigenetic alterations are required for progression from precancerous disease to...Persistent infection wit h high-risk types of human papillomavirus(HPV) is known to cause cervical cancer;however,additional genetic and epigenetic alterations are required for progression from precancerous disease to invasive cancer.DNA methylation is an early and frequent molecular alteration in cervical carcinogenesis.In this review,we summarize DNA methylation within the HPV genome and human genome and identify its clinical implications.Methylation of the HPV long control region(LCR) and L1 gene is common during cervical carcinogenesis and increases with the severity of the cervical neoplasm.The L1 gene of HPV16 and HPV18 is consistently hypermethylated in invasive cervical cancers and can potentially be used as a clinical marker of cancer progression.Moreover,promoters of tumor suppressor genes(TSGs) involved in many cellular pathways are methylated in cervical precursors and invasive cancers.Some are associated with squamous cell carcinomas,and others are associated with adenocarcinomas.Identification of methylated TSGs in Pap smear could be an adjuvant test in cervical cancer screening for triage of women with high-risk HPV,atypical squamous cells of undetermined significance,or low grade squamous intraepithelial lesion(LSIL).However,consistent panels must be validated for this approach to be translated to the clinic.Furthermore,reversion of methylated TSGs using demethylating drugs may be an alternative anticancer treatment,but demethylating drugs without toxic carcinogenic and mutagenic properties must be identified and validated.展开更多
Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe ...Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe the prevalence of HPV infection in different types of cervical lesions and to explore the relation between HPV viral load and the severity of cervical lesions. Methods To describe the HPV infection prevalence and viral load in different age groups, we retrospectively investigated 6405 cases of women who were organized by their units to take health-examination. They were given Hybrid Capture II tests between January 2005 and December 2006. The correlation between HPV viral load and pathology was assessed. Results Overall HPV infection prevalence was 29.1% （1864/6405）, while in women 18-20 years old it was 54.4% （31/57）, the highest among all age groups. After declining rapidly, HPV prevalence stabilized at about 30.0% in women aged 30 and older. Of the 6405 women, 1483 women had a colposcopic biopsy and 33.2% （492/1483） were positive for HPV DNA. Twenty-one percent of women with a normal diagnosis （238/1095） had HPV infection, a statistically significantly lower prevalence than in women with cervical lesions, including those with cervical intraepithelial neoplasia （68.8% in CIN1,66.7% in CIN2, and 76.5% in CIN3） or with cervical cancer （94.1%）. The correlation coefficient between viral load and cervical lesion severity was 0.134, which was not statistically significant （P=0.075）. Viral load values in women with CINs and cervical cancer were calculated, and no significant differences were identified. Conclusions The prevalence of high-risk HPV infection among women attending hospitals for health-examination in Shanghai is similar to the worldwide rate. HPV viral load can distinguish cervical lesions from normal individuals but cannot adequately predict the severity of cervical lesions.展开更多
Background:Primary human papillomavirus(HPV)screening is recommended for the detection of cervical intraepithelial neoplasia(CIN)in the general pop-ulation;however,the triage for HPV-positive women remains a challenge...Background:Primary human papillomavirus(HPV)screening is recommended for the detection of cervical intraepithelial neoplasia(CIN)in the general pop-ulation;however,the triage for HPV-positive women remains a challenge.This study aimed to evaluate the age-specific effectiveness of primary HPV screening versus primary cytology screening for identifying optimal strategies for women of different ages.Methods:The dataset of the prevalence round screening was derived from the National Cervical Cancer Screening Program in China.Primary cervical screen-ing protocols included cytology only,HPV testing with cytology triage,and HPV testing with HPV-16/18 genotyping plus cytology triage.The primary outcomes were age-specific detection rate,colposcopy referral rate and positive predictive value(PPV)for CIN2+.Multivariate Poisson regression was used to evaluate the relativeeffectivenessofHPVtestingandcytologyaccordingtoagegroups.TheI 2 statisticwitharandom-effectmodelwasusedtotesttheheterogeneityinrelative effectiveness of HPV testing versus cytology between age groups.Results:This study included 1,160,981 women.HPV testing with HPV-16/18 genotyping plus cytology triage significantly increased the CIN2+detection by 36%(rate ratio[RR]:1.36,95%confidential interval[CI]1.21–1.54)for women aged 35-44 years and by 34%(RR:1.34,95%CI 1.20-1.51)for women aged 45-54 years compared with cytology only.HPV testing with cytology triage had simi-lar CIN2+detection rate compared with cytology only.The PPVs were substan-tially increased for both HPV testing groups.Among women aged 55-64 years old,HPV testing with HPV-16/18 genotyping plus cytology triage increased the colposcopyreferralrateby19%(RR1.19,95%CI1.10-1.29)comparedwithcytology only,butdidnotincreasetheCIN2+detection(1.09,0.91–1.30).Theeffectiveness ofHPVtestingwithcytologytriagedidnotchangeinolderwomen.Thebetween-age-group heterogeneity in the effectiveness was statistically significant for HPV testing with HPV-16/18 genotyping plus cytology triage versus cytology only.Conclusions:Our results suggested that the effectiveness of primary HPV screeningwithdifferenttriagestrategiesdifferedamongagegroups.HPVtesting with HPV-16/18 genotyping plus cytology triage could be used for women aged 35-54 years to detect more lesions,and HPV testing with cytology triage could balance the CIN2+detection and the number of colposcopies for women aged 55-64 years.Longitudinal data including both prevalence and incidence screen-ing rounds are warranted to assess age-specific triage strategies.展开更多
文摘Objective To study the relationship between cell proliferation and apoptosis in cervical carcinoma and its clinical significance. Methods The cell proliferation and apoptosis of cervical epithelial cells in archival formalin-fixed, paraffin-embedded tissue sections of normal cervix, cervical intraepithelial neoplasms (GIN) and cervical squamous carcinoma were tested by using immunohistochemistry assay and DNA nick end-labeling technigue. The proliferation index (PI) and apoptosis index (AI) were calculated and their correlation with clinical and pathological data was analyzed.Results PI was gradually increased, but the AI and AI/PI ratio decreased from normal cervical epithelium, GIN to cervical carcinoma. There was no significant relationship among cell proliferation, apoptosis, clinical stages and pathological grades. High AI was always associated with a poor prognosis of the patients.Conclusion Cell proliferation and apoptosis allow to distinguish among normal epithelium, GIN and cervical carcinoma and are useful for the assessment of the malignant potential of tumor tissues.
文摘Persistent infection wit h high-risk types of human papillomavirus(HPV) is known to cause cervical cancer;however,additional genetic and epigenetic alterations are required for progression from precancerous disease to invasive cancer.DNA methylation is an early and frequent molecular alteration in cervical carcinogenesis.In this review,we summarize DNA methylation within the HPV genome and human genome and identify its clinical implications.Methylation of the HPV long control region(LCR) and L1 gene is common during cervical carcinogenesis and increases with the severity of the cervical neoplasm.The L1 gene of HPV16 and HPV18 is consistently hypermethylated in invasive cervical cancers and can potentially be used as a clinical marker of cancer progression.Moreover,promoters of tumor suppressor genes(TSGs) involved in many cellular pathways are methylated in cervical precursors and invasive cancers.Some are associated with squamous cell carcinomas,and others are associated with adenocarcinomas.Identification of methylated TSGs in Pap smear could be an adjuvant test in cervical cancer screening for triage of women with high-risk HPV,atypical squamous cells of undetermined significance,or low grade squamous intraepithelial lesion(LSIL).However,consistent panels must be validated for this approach to be translated to the clinic.Furthermore,reversion of methylated TSGs using demethylating drugs may be an alternative anticancer treatment,but demethylating drugs without toxic carcinogenic and mutagenic properties must be identified and validated.
文摘Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe the prevalence of HPV infection in different types of cervical lesions and to explore the relation between HPV viral load and the severity of cervical lesions. Methods To describe the HPV infection prevalence and viral load in different age groups, we retrospectively investigated 6405 cases of women who were organized by their units to take health-examination. They were given Hybrid Capture II tests between January 2005 and December 2006. The correlation between HPV viral load and pathology was assessed. Results Overall HPV infection prevalence was 29.1% （1864/6405）, while in women 18-20 years old it was 54.4% （31/57）, the highest among all age groups. After declining rapidly, HPV prevalence stabilized at about 30.0% in women aged 30 and older. Of the 6405 women, 1483 women had a colposcopic biopsy and 33.2% （492/1483） were positive for HPV DNA. Twenty-one percent of women with a normal diagnosis （238/1095） had HPV infection, a statistically significantly lower prevalence than in women with cervical lesions, including those with cervical intraepithelial neoplasia （68.8% in CIN1,66.7% in CIN2, and 76.5% in CIN3） or with cervical cancer （94.1%）. The correlation coefficient between viral load and cervical lesion severity was 0.134, which was not statistically significant （P=0.075）. Viral load values in women with CINs and cervical cancer were calculated, and no significant differences were identified. Conclusions The prevalence of high-risk HPV infection among women attending hospitals for health-examination in Shanghai is similar to the worldwide rate. HPV viral load can distinguish cervical lesions from normal individuals but cannot adequately predict the severity of cervical lesions.
基金NationalNatural Science Foundation of China,Grant/Award Number:81903328Key Project of PublicHealth Program+2 种基金study was supported by grants from the National Nat-ural Science Foundation of China(grant no 81903328)and the Chinese Key Project of Public Health Program.The funderswere not involved in the design,conduct,or report-ing of the studythe writing of the manuscriptor the deci-sion to publish the manuscript.
文摘Background:Primary human papillomavirus(HPV)screening is recommended for the detection of cervical intraepithelial neoplasia(CIN)in the general pop-ulation;however,the triage for HPV-positive women remains a challenge.This study aimed to evaluate the age-specific effectiveness of primary HPV screening versus primary cytology screening for identifying optimal strategies for women of different ages.Methods:The dataset of the prevalence round screening was derived from the National Cervical Cancer Screening Program in China.Primary cervical screen-ing protocols included cytology only,HPV testing with cytology triage,and HPV testing with HPV-16/18 genotyping plus cytology triage.The primary outcomes were age-specific detection rate,colposcopy referral rate and positive predictive value(PPV)for CIN2+.Multivariate Poisson regression was used to evaluate the relativeeffectivenessofHPVtestingandcytologyaccordingtoagegroups.TheI 2 statisticwitharandom-effectmodelwasusedtotesttheheterogeneityinrelative effectiveness of HPV testing versus cytology between age groups.Results:This study included 1,160,981 women.HPV testing with HPV-16/18 genotyping plus cytology triage significantly increased the CIN2+detection by 36%(rate ratio[RR]:1.36,95%confidential interval[CI]1.21–1.54)for women aged 35-44 years and by 34%(RR:1.34,95%CI 1.20-1.51)for women aged 45-54 years compared with cytology only.HPV testing with cytology triage had simi-lar CIN2+detection rate compared with cytology only.The PPVs were substan-tially increased for both HPV testing groups.Among women aged 55-64 years old,HPV testing with HPV-16/18 genotyping plus cytology triage increased the colposcopyreferralrateby19%(RR1.19,95%CI1.10-1.29)comparedwithcytology only,butdidnotincreasetheCIN2+detection(1.09,0.91–1.30).Theeffectiveness ofHPVtestingwithcytologytriagedidnotchangeinolderwomen.Thebetween-age-group heterogeneity in the effectiveness was statistically significant for HPV testing with HPV-16/18 genotyping plus cytology triage versus cytology only.Conclusions:Our results suggested that the effectiveness of primary HPV screeningwithdifferenttriagestrategiesdifferedamongagegroups.HPVtesting with HPV-16/18 genotyping plus cytology triage could be used for women aged 35-54 years to detect more lesions,and HPV testing with cytology triage could balance the CIN2+detection and the number of colposcopies for women aged 55-64 years.Longitudinal data including both prevalence and incidence screen-ing rounds are warranted to assess age-specific triage strategies.
