OBJECTIVE: To investigate the expression of claudin 4 (CLDN4) in cervical tissues from patients with different cervical lesions, and to explore the value of combined detection of CLDN4 and high risk human papilloma virus (HR-HPV). METHODS: The cervical tissue specimens of low-grade squamous intraepithelial lesion (LSIL, =30), high-grade squamous intraepithelial lesion (HSIL, =30), squamous cell carcinoma (SCC, =30) as well as chronic cervicitis (control, =30) were collected from the Sir Run Run Shaw Hospital of Zhejiang University during June 2015 and December 2016. The expression of CLDN4 protein in tissue specimens was detected by immunohistochemistry, HR-HPV was detected by real-time quantitative PCR, and the cervical exfoliated cells were examined by thinprep cytologic test (TCT). The ROC curve was applied to analyze the diagnostic value of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for HSIL and SCC of the cervix. RESULTS: With the increase of the severity of cervical lesions, the positive rate of CLDN4 expression rose (=0.832, <0.05). Positivity of both HR-HPV infection and CLDN4 expression was found mainly in the HSIL and SCC groups. The areas under curve (AUC) of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for diagnosis of HSIL and SCC were 0.683 and 0.633, respectively; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of TCT combined with HR-HPV test for diagnosis of HSIL and SCC were 100.0%, 36.7%, 61.2%, 100.0% and 46.7% respectively; those of CLDN4 combined with HR-HPV test were 96.7%, 30.0%, 58.0%, 90.0% and 55.0%, respectively. CONCLUSIONS CLDN4 expression may be related to the occurrence and development of cervical carcinoma and precancerous lesions. CLDN4 combined with HR-HPV test may be used for diagnosis of HSIL and SCC of the cervix clinically.
Carcinoma, Squamous Cell ; diagnosis ; virology ; Cervical Intraepithelial Neoplasia ; diagnosis ; virology ; Claudin-4 ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunochemistry ; Papillomaviridae ; isolation & purification ; Real-Time Polymerase Chain Reaction ; Squamous Intraepithelial Lesions of the Cervix ; virology ; Uterine Cervical Neoplasms ; diagnosis

OBJECTIVE: This study was conducted using the human papillomavirus (HPV) DNA chip test (HDC), in order to determine whether the HPV genotype is a predictor of residual disease in a subsequent hysterectomy following a loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 3. METHODS: Between January 2002 and February 2015, a total of 189 patients who underwent a hysterectomy within 6 months of LEEP caused by CIN 3 were included in this study. We analyzed their epidemiological data, pathological parameters, high-risk HPV (HR-HPV) load as measured by the hybrid capture II assay, and HR-HPV genotype as measured by the HDC. A logistic regression model was used to analyze the relationship between covariates and the probability of residual disease in subsequent hysterectomy specimens. RESULTS: Of the 189 patients, 92 (48.7%) had residual disease in the hysterectomy specimen, CIN 2 in seven patients, CIN 3 in 79 patients, IA1 cancer in five patients, and IA2 cancer in one patient. Using multivariate analysis, the results were as follows: cone margin positivity (odds ratio [OR], 2.43; 95% CI, 1.18 to 5.29; p<0.05), HPV viral load > or =220 relative light unit (OR, 2.98; 95% CI, 1.38 to 6.43; p<0.01), positive endocervical cytology (OR, 8.97; 95% CI, 3.81 to 21.13; p<0.001), and HPV-16 or HPV-18 positivity (OR, 9.07; 95% CI, 3.86 to 21.30; p<0.001). CONCLUSION: The HPV-16 or HPV-18 genotype is a reliable predictive factor of residual disease in a subsequent hysterectomy following a LEEP for CIN 3.
Adult ; Aged ; Aged, 80 and over ; Cervical Intraepithelial Neoplasia/*surgery/virology ; Electrosurgery/methods ; Female ; Genotype ; Genotyping Techniques/methods ; Human papillomavirus 16/genetics/*isolation & purification ; Human papillomavirus 18/genetics/*isolation & purification ; Humans ; Hysterectomy ; Middle Aged ; Neoplasm, Residual ; Papillomavirus Infections/*virology ; Prognosis ; Retrospective Studies ; Uterine Cervical Neoplasms/*surgery/virology ; Viral Load

OBJECTIVE: We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). METHODS: Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. RESULTS: The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). CONCLUSION: Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.
Cervical Intraepithelial Neoplasia/pathology/surgery/*virology ; Female ; Humans ; Neoplasm Recurrence, Local/*virology ; Neoplasm, Residual ; Papillomaviridae/*isolation & purification ; Papillomavirus Infections/complications/*diagnosis ; Predictive Value of Tests ; Risk Assessment/methods ; Sensitivity and Specificity ; Uterine Cervical Neoplasms/pathology/surgery/*virology

No abstract available.
Cervical Intraepithelial Neoplasia/*virology ; Female ; Humans ; *Papillomaviridae ; Papillomavirus Infections ; Uterine Cervical Dysplasia ; Uterine Cervical Neoplasms/virology

OBJECTIVE: Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the major cause of invasive cervical cancers. HPV-16 and HPV-18 are known to be responsible for two-thirds of all invasive cervical carcinomas, followed by HPV-45, -31, and -33. Current guidelines only differentiate HPV-16/18 (+) by recommending direct colposcopy for treatment. We tried to evaluate whether there are differences in risk among 12 non-16/18 HR-HPV genotypes in this study. METHODS: The pathology archive database records of 1,102 consecutive gynecologic patients, who had results for cervical cytology and histology and for HPV testing, as determined by HPV 9G DNA chip, were reviewed. RESULTS: Among the 1,102 patients, 346 were non-16/18 HR-HPV (+) and 231 were HPV-16/18 (+). We calculated the odds ratios for ≥cervical intraepithelial neoplasia 2 (CIN 2) of 14 groups of each HR-HPV genotype compared with a group of HR-HPV (–) patients. Based on the odds ratio of each genotype, we divided patients with non-16/18 HR-HPV genotypes (+) into two groups: HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+). The age-adjusted odds ratios for ≥CIN 2 of the HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+) groups compared with a HR-HPV (–) group were 11.9 (95% CI, 7.6 to 18.8; p<0.001) and 2.4 (95% CI, 1.4 to 4.3; p<0.001), respectively, while that of the HPV-16/18 (+) group was 18.1 (95% CI, 11.6 to 28.3; p=0.003). CONCLUSION: The 12 non-16/18 HR-HPV genotypes can be further categorized (HPV-31/33/35/45/52/58 vs. HPV-39/51/56/59/66/68) by risk stratification. The HPV-31/33/35/45/52/58 genotypes might need more aggressive action. Large scale clinical trials or cohort studies are necessary to confirm our suggestion.
Adult ; Cervical Intraepithelial Neoplasia/*virology ; Colposcopy ; DNA, Viral/analysis ; Female ; *Genotype ; Human papillomavirus 16/genetics ; Human papillomavirus 18/genetics ; Humans ; Middle Aged ; Papanicolaou Test ; Papillomaviridae/*genetics ; Papillomavirus Infections/*virology ; Risk Factors ; Uterine Cervical Neoplasms/virology ; Vaginal Smears

OBJECTIVETo investigate the expression of cyclin D1 in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma and its relationship with human papillomavirus 16 (HPV16) E7 gene expression.

METHODSBoth SiHa and Hcc94 cell lines were obtained from cervical epithelial cells of squamous cell carcinoma. E6/E7 gene was silent in Hcc94 cell line.Expression levels of cyclin D1 mRNA and protein in CIN and squamous cell carcinoma were detected by QT-PCR and immunohistochemistry (IHC) respectively. SiRNA was constructed for targeting the promoter of HPV16 E7 and then transfected into SiHa cells to establish cm-16 line with stable silencing of E7. Control cell line B3 was obtained by blank plasmid transfection into SiHa cells. RT-PCR and Western blot were used to detect cyclin D1 mRNA and protein expression in the SiHa, B3, and cm-16 cells, respectively.

RESULTSCyclin D1 was expressed in the basal cells of normal cervical squamous epithelia and the expression gradually decreased in the progression from CIN1 to CIN3. Squamous cell carcinoma showed negative or scattered expression of cyclin D1 (P<0.05). Both mRNA and protein of cyclin D1 in E7(+) SiHa cells were lower than those in cm-16 and Hcc94 cells.

CONCLUSIONSquamous cell carcinoma with high HPV E7 expression shows low level of cyclin D1, suggesting that HPV16 E7 gene inhibits the expression of cyclin D1.

Carcinoma, Squamous Cell ; metabolism ; virology ; Cell Line, Tumor ; Cervical Intraepithelial Neoplasia ; metabolism ; virology ; Cyclin D1 ; genetics ; metabolism ; Female ; Human papillomavirus 16 ; Humans ; Immunohistochemistry ; Papillomavirus E7 Proteins ; genetics ; Promoter Regions, Genetic ; RNA Interference ; RNA, Messenger ; RNA, Small Interfering ; Transfection ; Uterine Cervical Neoplasms ; metabolism ; virology

OBJECTIVETo investigate the prevalence of physical state of HPV-16 DNA in cervical cancer and cervical precancerous carcinoma.

METHODSMultiplex PCR was adopted to detect the physical state of HPV in samples from 252 patients with cervical carcinoma, including 48 samples of cervical cancer, 204 cervical intraepithelial neoplasia (CIN ) (125 CIN I, 46 CIN II and 33 CIN III) and 20 normal samples from the subjects with hysteromyoma undergoing hysterectomy, respectively.

RESULTSAmong 48 patients with cervical cancer, 31 (65.6%) were infected with HPV-16. Eighteen among 31 (58.1%) HPV-16 infected patients with cervical cancer were found to have integrated infection of HPV-16. The positive rates of HPV-16 infection in the patients with CIN I, CIN II and CIN III were 19.2%, 34.8% and 42.4%, and the integrated infection rates of HPV-16 were 16.7%, 18.8% and 35.7%, respectively. Compared with patients with different grades of CIN, the integrated rate of HPV-16 infection in those with cervical cancer was significantly elevated.

CONCLUSIONAmong the patients with HPV-16 infection, the integrated state of HPV-16 is positively correlated with the severity of cervical lesions. Combined HPV typing test and detection of integrated viral state contribute to predicting the prognosis of patients with cervical precancerous lesions and increasing the accuracy of screening cervical cancer on the basis of HPV DNA detection.

Cervical Intraepithelial Neoplasia ; virology ; DNA, Viral ; Early Detection of Cancer ; Female ; Human papillomavirus 16 ; physiology ; Humans ; Papillomavirus Infections ; virology ; Uterine Cervical Neoplasms ; virology ; Virus Integration

OBJECTIVETo investigate human papilloma virus (HPV) infection and typing in 7 640 cases of women in Shanxi province in order to provide theoretical basis for the prevention and treatment of the cervical cancer.

METHODSTotally, 7 640 cases of cervical cell specimens in Shanxi provincial tumor hospital, screening and physical examination from 2012 January to 2013 May and 23 HPV genotypes were analyzed by PCR and reverse dot blot gene chip technology.

RESULTSA total of 1 441 cases of patients with HPV infection were to be found in 7 640 cases of women with an average age of (42.26 ± 19.15)years old. The total infection positive rate, infection rate of high-risk HPV, infection rate of low-risk HPV and infection rate of mixed high and low risk were 18.86% (1 441/7 640), 16.03% (1 225/7 640, including multiple high-risk of HPV infection), 4.88% (373/7 640, including multiple low-risk of HPV infection) and 2.05% (157/7 640) respectively. The rate of high-risk HPV infection was 85.01% (1 225/1 441) in total infection positive women. The most common subtype was HPV16 (34.70%, 523/1 507) and followed by HPV58 (11.48%, 173/1 507), HPV18 (7.43%, 112/1 507), HPV33 (7.10%, 107/1 507), HPV56 (6.04%, 91/1 507) and HPV52 (5.51%, 83/1 507) respectively in tested 18 high-risk HPV subtypes, and there was no HPV82. The most common subtype was HPV43 (38.13%, 151/396) and followed by HPV42 (22.22%, 88/396), HPV81 (20.45%, 81/396), HPV6 (11.87%, 47/396) and HPV11 (7.32%, 29/396) respectively in tested 5 low-risk HPV subtypes. The HPV infection positive rates were significantly different in different age groups and HPV total infection rate, high-risk infection rate in 41-50 year-old age group was the highest, 23.23%. The infection rates of single subtype of HPV and single high-risk subtype of HPV were 75.71% (1 091/1 441) and 61.35% (884/1 441) respectively in all cases of infection women and single high-risk subtype infection rate was 81.03% (884/1 091) in all cases of single subtype infection women. The infection rate of multiple subtype of HPV was 24.29% (350/1 441) in all cases with HPV infection. The double infections was most common (18.18%, 262/1 441) in which the women of double high-risk infections of HPV were 151 cases (10.48%, 151/1 441). The rates of double infection, triple infection and quadruple or more infection of HPV were 74.86% (262/350), 20.29% (71/350) and 4.89% (17/350) respectively in all cases with HPV multiple infection. The positive rates of HPV infection in different age groups were obvious difference. The positive rate of single infection of HPV was 17.80% (574/3 224) in cases of 41-50 years old group which higher than that in other groups(χ² = 20.18, P < 0.05).

CONCLUSIONThe more common high-risk HPV subtype is HPV16, HPV58, HPV18, HPV33, HPV56 and HPV52 and low-risk HPV subtype is HPV43, HPV42 in Shanxi province. HPV infection is most common in the age group of 41- 50 years old female.

Adult ; Aged ; Cervical Intraepithelial Neoplasia ; epidemiology ; virology ; China ; epidemiology ; Cross-Sectional Studies ; DNA, Viral ; genetics ; Female ; Genotype ; Human papillomavirus 16 ; genetics ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Papillomaviridae ; classification ; genetics ; Papillomavirus Infections ; epidemiology ; virology ; Risk Factors ; Uterine Cervical Neoplasms ; epidemiology ; virology ; Young Adult

OBJECTIVETo investigate the prevalence of genital human papillomavirus (HPV) infection among women in Shaan'xi Province of China, and to detect the characteristics of genital HPV infection among these women.

METHODSTotally 8581 women in the Department of Gynaecology of the First Affiliated Hospital of Xi'an Jiaotong University were enrolled to detect HPV-DNA in their genital tracts by PCR+flow-through hybridization. Some subjects were also screened by cytology or histology.

RESULTSAmong these subjects, the prevalence of female genital tract HPV infection was 33.06%, among which high risk (HR)-HPV infection accounted for 30.08% and multiple HR-HPV infection 27.18%. The genotypes HPV-16, -52,-58, -6, and HPV-18 were the most prevalent strains. The distribution of HPV infection differed among different age groups:the first infection peak occured less than 25 years and the second peak was above 51 years. Among the HR-HPV DNA positive women, the rates of HR-HPV infection with normal histology, cervical intraepithelial neoplasias 1 (CIN1), CIN2 ,CIN3, and cervical cancer (CC) were 88.72%, 97.48%, 97.35%, 95.88%, and 99.23%, respectively. For women with CC, HPV-16 was the most common genotype, followed by HPV-18, HPV-58, HPV-52, and HPV-33. HPV-16 ,-18, and 58 were responsible for 94.62% of CC cases in this region.

CONCLUSIONSThe most common genotypes of HPV infection among women in Shaan'xi province are HPV-16, HPV-52, HPV-58, HPV-6, and HPV-18. HPV-16, HPV-18, HPV-58, HPV-52, and HPV-33 are the most frequently genotypes found in cervical carcinoma, in particular HPV-16, HPV-18, and HPV-58. HR-HPV infection aggravates the cervical lesions. The multiple HPV infections increase the risk of cervical lesions.

Adolescent ; Adult ; Aged ; Cervical Intraepithelial Neoplasia ; epidemiology ; virology ; China ; epidemiology ; DNA, Viral ; isolation & purification ; Female ; Genotype ; Humans ; Mass Screening ; Middle Aged ; Papillomaviridae ; classification ; isolation & purification ; Papillomavirus Infections ; epidemiology ; Prevalence ; Reproductive Tract Infections ; epidemiology ; virology ; Young Adult

OBJECTIVETo evaluate the diagnostic performance of different specimens for detecting CIN2(+), and to find the solution of the problem that why the performance of self-collected specimen is worse than cervical specimen collected by physician.

METHODSThe cervix, lower 1/3 vagina, upper 1/3 vagina and self-collected specimens from each of the 806 women who took part in this multi-center screening program from May 2006 to April 2007 were tested by hybrid capture 2 (HC2) technique. The diagnostic performance of HC2 on the four specimens for detecting CIN2(+) lesions was calculated. Linear array was performed on the four specimens from 489 out of the 806 women and the diagnostic performance of linear array on the four specimens for detecting CIN2(+) lesions was also calculated. Z test was used to compare the area under ROC and McNemar or χ(2) test was used to compare the sensitivity and specificity of different specimens.

RESULTSThe area under ROC of the cervix, 1/3 upper vagina, 1/3 lower vagina and self-collected samples testing by HC2 for detecting CIN2(+) lesions were 0.902, 0.793, 0.769 and 0.773, respectively (P < 0.001). Using 1 RUL/CO as the cut-point of HC2, the sensitivity of the cervix, upper vagina, lower vagina and self-collected samples were 98.0%, 91.8%, 83.7% and 81.6%. Compared with the cervical specimen, the sensitivity of self-collected specimen for detecting CIN2(+) lesions was significantly lower (P = 0.008). Lowering the cutoff value for HC2 test could improve the sensitivity of self-collected specimen, but it significantly compromised the specificity. The sensitivity of self-collected specimen tested by linear array for detecting CIN2(+) lesions was 95.7% and it was not significantly different compared with the sensitivity of cervical specimen (97.9%) tested by HC2.

CONCLUSIONSThe performance of self-collected specimen tested by HC2 for detecting CIN2(+) lesions is lower than that of physician-collected cervical specimen, and lowering the cutoff value can't improve its diagnostic performance. Using linear array as the HPV DNA test can significantly improve the screening diagnostic performance of self-collected specimens.

Adolescent ; Cervical Intraepithelial Neoplasia ; diagnosis ; virology ; Cervix Uteri ; virology ; DNA, Viral ; analysis ; Female ; Human Papillomavirus DNA Tests ; Humans ; Mass Screening ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; diagnosis ; virology ; Self-Examination ; Specimen Handling ; methods ; Uterine Cervical Neoplasms ; diagnosis ; virology ; Vagina ; virology