OBJECTIVETo determine the association between viral load of high risk human papillomavirus (HR-HPV) and cervical intraepithelial neoplasia (CIN).

METHODSCervical exfoliated cells were collected from 18 186 women aged 17 -59 from six urban areas and eight rural areas when they were screened in the cross-sectional population-based studies from 1999 to 2008. HR-HPV was detected by the Hybrid Capture 2 (hc2) system, and viral load was measured by the ratio of relative light units to standard positive control (RLU/PC). RLU/PC was categorized for analysis into four groups: negative [0, 1.00), low viral load [1.0, 10.00), moderate viral load [10.00, 100.00), and high viral load > or = 100.00. Cervical lesions were diagnosed by biopsies as normal, CIN 1, CIN 2, CIN 3 and squamous cervical cancer (SCC). Association between HR-HPV viral load and CIN was evaluated by unconditional multinomial logistic regression.

RESULTSThe HR-HPV infection rate of the population was 14.51% (2515/17334). 100.00% (29/29) of SCC, 97.63% (206/211) of CIN 3, 93.43% (199/213) of CIN 2, 75.04% (421/561) of CIN 1 and 10.17% (1660/16320) of normal women were positive for HR-HPV DNA. The median RLUs for the HR-HPV positive women with SCC, CIN 3, CIN 2, CIN 1 and normal were 320.85, 158.05, 143.70, 125.34 and 9.64, respectively. There were significant differences among the distributions of viral loads in each lesion (chi2 = 6190.40, P < 0.01). The severity of CIN increased with the viral load (chi2 = 5493.35, P <0.01). Compared with the risks of CINs in HR-HPV negative population, the risks of CINs in low, moderate and high viral loads were increased gradually [OR(95% CI) : CIN 1 : 9.01(6.31 - 12.87), 24.96(18.23 - 34.17) and 68.42(51.40 - 91.08); CIN 2 : 26.44(12.07 - 57.95), 98.53(49.54 - 195.98) and 322.88(168.62 - 618.27); CIN 3+ : 72.89(24.02-221.18); 343.58(121.81-969.09) and >999.99(473.38 - >999.99)], and there were obvious dose-response relationships (chi2trend was 3115.05, 2413.95 and 3098.57, respectively. P< 0.01). In each age group of the HR-HPV positive population,the risks of CIN 2 + in the women with moderate or high viral load were higher than the one with low viral load [OR(95% CI): <35 : 4.71(1.23 - 18.09) and 15.06(4.40 - 51.49); 35 -: 4.01 (1.62 -9.90) and 14.09(6.15 -32.28); 40 - : 3.06(1.52 -6.16) and 7.78(4.05 -14.95); > or =45: 3.50(1.36 -9. 01) and 7.57(3.13 - 18. 30)], and there was a positive correlation between the risk of CIN 2+ and the viral load (chi2trend was 51.33, 66.28, 53.64 and 51.00, respectively. P <0.01). The risk of CIN 2 + was highest among the women aged 40 - with high viral load [OR (95% CI) : 2.02 (1.15 - 3.52)].

CONCLUSIONThere is strong correlation between the HR-HPV viral load and the severity of CIN, and so is the correlation between the HR-HPV viral load and the risk of CIN 2 +. A moderate to high viral load of HR-HPV should be the major risk factor for the cervical cancer and CIN 2 and CIN 3, and there is a higher risk in the women aged 35 or older than the younger ones. Considering both the age and viral load could help the doctors to manage the screening women more effectively.

Adult ; Cervical Intraepithelial Neoplasia ; epidemiology ; pathology ; virology ; Cervix Uteri ; pathology ; virology ; Female ; Humans ; Middle Aged ; Papillomavirus Infections ; epidemiology ; pathology ; virology ; Risk Factors ; Uterine Cervical Neoplasms ; epidemiology ; pathology ; virology ; Viral Load

PURPOSE: Human papillomavirus (HPV) infection is a well-known cause of cervical cancer, which, along with its precursors, can be diagnosed and treated with cervical conization (CC). This study aimed to assess HPV- and procedure-related knowledge among women who had undergone CC. MATERIALS AND METHODS: Between February and May 2014, consecutive women who had undergone CC at five different educational hospitals were recruited. All patients had undergone a loop electrosurgical excision procedure as the method of CC. A survey was conducted with a self-developed, 29-item questionnaire, measuring knowledge related to HPV and CC. We analyzed the responses of 160 patients who completed the questionnaire. RESULTS: Mean total knowledge scores (±standard deviation) for HPV and CC were 5.2±3.0 of a possible 13.0 and 8.3±4.2 of a possible 16.0, respectively. While 73% of the patients knew that HPV is the main cause of cervical cancer, only 44% knew that HPV is sexually transmitted. The purpose of CC was correctly identified by 71% of the patients. However, 35% failed to indicate the anatomical area resected at the time of CC in the schematic diagram. Women who were younger (p<0.001), had higher education level (p<0.001), and higher family income (p=0.008) had higher knowledge scores. In contrast, neither interval from CC to survey nor disease severity were associated with total knowledge score. CONCLUSION: The level of knowledge related to HPV and CC was unexpectedly low in women who had undergone CC. Intuitive educational resources may improve this knowledge, and further cohort studies are warranted.
Adult ; Cervix Uteri/*pathology/*virology ; *Conization ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Middle Aged ; Papillomaviridae/*physiology ; Republic of Korea ; Sexual Behavior ; *Surveys and Questionnaires ; Uterine Cervical Neoplasms/virology ; Young Adult

OBJECTIVETo evaluate the correlation of the expression of homeodomain-interacting protein kinase 2 (HIPK2) with human papillomavirus (HPV) infection and apoptosis in cervical cancer.

METHODSFormalin-fixed, paraffin embedded tissue samples from 50 cervical cancers and 15 normal uterine cervix cases were obtained. Apoptosis was quantified by TdT-mediated dUTP nick end labeling (TUNEL) assay and the expression of HIPK2 as well as HPV by immunohistochemical staining.

RESULTSHIPK2 protein expression was detected in 88.0% (44/50) of cervical cancers and 6.7% (1/15) of normal cervical tissues. HPV was found in 78.0% (39/50) of cervical cancers and 20.0% (3/15) of normal cervical tissue samples. The expression of HIPK2 protein was significantly and positively correlated with HPV presence (r=0.467, P<0.01), but negatively with apoptotic index (r=-0.370, P<0.05).

CONCLUSIONHIPK2 protein expression is positively correlated with HPV infection, but negatively with apoptotic index in cervical cancers. Therefore, HIPK2 may be involved in the mechanism of apoptosis in cervical cancer and may play an important role in cervical carcinogenesis.

Adenocarcinoma ; metabolism ; pathology ; virology ; Apoptosis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; virology ; Carrier Proteins ; metabolism ; Cervix Uteri ; metabolism ; Female ; Humans ; Middle Aged ; Papillomaviridae ; Papillomavirus Infections ; Proliferating Cell Nuclear Antigen ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; virology

OBJECTIVETo evaluate the value of high-risk HPV (hrHPV) detection by Hybrid Capture II (HC2) in screening cervical intraepithelial neoplasm (CIN).

METHODSTotally 723 patients who had received a dual screening with thinprep cytologic test (TCT) and HC2 in our department were analyzed retrospectively. Among them, 350 patients received a triple examination with TCT, HC2, and colposcopic biopsy.

RESULTSAmong the 723 patients, the incidences of hrHPV infection with atypical squamous cell (ASC), low squamous intraepithelial lesion, and high squamous intraepithelial lesion were 70.7% (94/133), 88.9% (249/280), and 90.9% (90/99), respectively, significantly higher than 55.5% (117/211), the incidence of hrHPV infection with normal cytological results (P = 0.005, P < 0.001, P < 0.001, respectively). Among 350 cases who were received triple examination, the incidence of hrHPV infection with cervical intraepithelial neoplasia (CIN) 1 and CIN 2 were 88.9% (72/81) and 96.3% (52/54), significantly higher than 77.7% (153/197), the incidence of hrHPV infection with normal pathological results (P = 0.03, P = 0.002); The incidence of hrHPV infection with CIN 3 and squamous cancer were 91.7% (11/12) and 100.0% (6/6), also higher than normal cases. Among these 350 cases, the incidence of hrHPV infection with ASC was 79.3% (69/87). The incidence of CIN 2-3 with ASC and hrHPV infection was 38.0%, significantly higher than the incidence of CIN 2-3 with ASC and without hrHPV infection (5.9%) (P = 0.04).

CONCLUSIONhrHPV infection has a close relation with CIN, and the incidence of hrHPV infection increases along with the severity of CIN.

Adolescent ; Adult ; Cervical Intraepithelial Neoplasia ; virology ; Cervix Uteri ; pathology ; virology ; Female ; Human papillomavirus 16 ; isolation & purification ; Human papillomavirus 18 ; isolation & purification ; Humans ; Middle Aged ; Nucleic Acid Hybridization ; methods ; Papillomavirus Infections ; epidemiology ; virology ; Uterine Cervical Neoplasms ; virology

OBJECTIVEThe aim of the study was to investigate the positivity of human papillomavirus (HPV) and the possible related risk factors for HPV infection in certain district government in Daqing city, Heilongjiang province.

METHODSA total of 2015 female staffs who participated cervical cancer screening were selected as subjects, in certain district government in Daqing city, Heilongjiang province, from June to October, 2010. First of all, a standardized questionnaire was used for collection of subject's demographic information and possible risk factors. Afterwards, cervical cytological and HPV DNA testing were applied to all participants. Subjects with suspected cervical intraepithelial neoplasia (CIN) or cervical cancer were recalled for taking biopsy under colposcopy for further histopathological diagnosis. Standardized HPV positivity by Segi's world population and compared the difference of HPV positivity of different types. The positivity of HPV between women with and without cervical abnormalities were compared by unconditional logistic regression. And the possible risk factors for HPV infection were also investigated.

RESULTSA total of 1759 out of 2015 subjects had gynecological examination, among which 152 subjects were HPV positive. The positivity of HPV was 8.64% (95%CI: 7.37% - 10.05%), and it was 8.47% (95%CI: 7.93% - 9.03%) after age standardization. Finally, 57 (3.24%) and 1702 (96.76%) subjects had abnormal (≥ CIN1 or low-grade squamous intraepithelial lesion (LSIL)) and normal cervix, respectively. The HPV positivity between women with and without cervical abnormalities were 73.68% (42/57) and 6.46% (110/1702), respectively. There was a significant difference (χ(2) = 307.23, P < 0.05) in HPV positivity between women with and without cervical abnormalities. The risk of cervical abnormalities for women with HPV positivity was 40.52 times (95%CI: 21.79 - 75.36) higher than that for women with HPV negativity. Among women with cervical abnormalities, the most three common HPV types, in descending order, were HPV16 (28.07% (16/57)), HPV52 (14.04% (8/57)) and HPV58 (12.28% (7/57)). While among women with normal cervix, the most three common HPV types were HPV52 (1.23% (21/1702)), HPV16 (1.00% (17/1702)) and HPV58 (0.71% (12/1702)). The positivity of HPV clade A9 among women with and without cervical abnormalities were 59.65% (34/57) and 3.23% (55/1702), which were higher than that of other clades. Analysis for risk factors of HPV infection showed that smoking (OR = 2.71, 95%CI: 1.00 - 7.33), late age (≥ 15 years old) of menarche (OR = 1.44, 95%CI: 1.00 - 2.05), early age (≤ 20 years old) of marriage (OR = 3.09, 95%CI: 1.30 - 7.35), multiple (≥ 2) sexual partners (OR = 2.69, 95%CI: 1.46 - 4.95), husband's extramarital sexual behaviors (OR = 2.77, 95%CI: 1.25 - 6.12) and multiple (≥ 2 times) parity (OR = 1.77, 95%CI: 1.03 - 3.03) would increase the risk of HPV positivity.

CONCLUSIONHPV positivity among women with cervical abnormalities was significantly higher than that among women with normal cervix. HPV16, 52, 58 were the major genotypes among the study population. Smoking, late age of menarche, early age of marriage, multiple sexual partners, husband extramarital sexual behaviors and multiple parity increase the risk of HPV infection.

Adult ; Aged ; Case-Control Studies ; Cervical Intraepithelial Neoplasia ; epidemiology ; virology ; Cervix Uteri ; pathology ; virology ; China ; epidemiology ; DNA, Viral ; isolation & purification ; Early Detection of Cancer ; Female ; Humans ; Middle Aged ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; epidemiology ; virology ; Risk Factors ; Young Adult

BACKGROUND: We evaluated the performance of various commercial assays for the molecular detection of human papillomavirus (HPV); the recently developed AdvanSure HPV Screening real-time PCR assay (AdvanSure PCR) and the Abbott RealTime High Risk HPV PCR assay (Abbott PCR) were compared with the Hybrid Capture 2 HPV DNA Test (HC2). METHODS: All 3 tests were performed on 177 samples, and any sample that showed a discrepancy in any of the 3 tests was genotyped using INNO-LiPA HPV genotyping and/or sequencing. On the basis of these results, we obtained a consensus HPV result, and the performance of each test was evaluated. We also evaluated high-risk HPV 16/18 detection by using the 2 real-time PCR assays. RESULTS: Among the 177 samples, 65 were negative and 75 were positive in all 3 assays; however, the results of the 3 assays with 37 samples were discrepant. Compared with the consensus HPV result, the sensitivities and specificities of HC2, AdvanSure PCR, and Abbott PCR were 97.6%, 91.7%, and 86.9% and 83.9%, 98.8%, and 100.0%, respectively. For HPV type 16/18 detection, the concordance rate between the AdvanSure PCR and Abbott PCR assays was 98.3%; however, 3 samples were discrepant (positive in AdvanSure PCR and negative in Abbott PCR) and were confirmed as HPV type 16 by INNO-LiPA genotyping and/or sequencing. CONCLUSIONS: For HPV detection, the AdvanSure HPV Screening real-time PCR assay and the Abbott PCR assay are less sensitive but more specific than the HC2 assay, but can simultaneously differentiate type 16/18 HPV from other types.
Adult ; Aged ; Cervix Uteri/pathology/virology ; DNA, Viral/analysis ; Female ; Genotype ; Human papillomavirus 16/genetics ; Human papillomavirus 18/genetics ; Humans ; Middle Aged ; Papillomaviridae/*genetics/isolation & purification ; Papillomavirus Infections/*diagnosis/pathology/virology ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; Young Adult

Adenocarcinoma ; genetics ; pathology ; virology ; Carcinoma in Situ ; genetics ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; genetics ; pathology ; virology ; Cervix Uteri ; pathology ; virology ; Cytological Techniques ; DNA, Viral ; analysis ; Female ; Follow-Up Studies ; Humans ; Neoplasm Grading ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; diagnosis ; Uterine Cervical Neoplasms ; genetics ; pathology ; virology

To evaluate PCR-sequencing for clinical detection of human papillomavirus (HPV) genotypes in cervical cell specimens, we applied PCR-sequencing to HPV detection and genotyping by general primer PGMY09/11, which targets the HPV most conserved L1 gene. Samples with multiple infections were subjected to HPV type-specific PCR. Among the 325 cervical samples, 228 were HPV positive, of which 66 showed multiple infections. In all, 27 different HPV genotypes were identified, with HPV 16 being the most prevalent, followed by HPV 58 and 52. The prevalence of high-risk HPV infection increased with the severity of cervical lesions (P < 0.05), whereas the proportion of multiple infections declined significantly from LSIL to SCC (P < 0.05). Both rates of overall and high-risk HPV infection were the highest in 21-30 age groups. There was substantial agreement between the HC2 and PCR-sequencing assay for detection of high-risk HPV (kappa = 0.675). PCR-sequencing was effective in HPV detection and genotyping, and it could be potentially applied to large scale HPV screening.
Adult ; Aged ; Cervix Uteri ; pathology ; virology ; China ; epidemiology ; Female ; Genotype ; Human papillomavirus 16 ; isolation & purification ; Humans ; Middle Aged ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; epidemiology ; virology ; Polymerase Chain Reaction ; methods ; Vaginal Smears ; Young Adult

OBJECTIVETo evaluate the etiological significance of human papillomavirus (HPV) in cervical cancer and the clinical utility of HPV detection in cervical cancer screening.

METHODSHybrid capture II test was used to detect 13 high-risk HPV genotypes from cervical scrapes of 2636 women. Cervical cytology was also evaluated in 454 of them by ThinPrep Pap smear.

RESULTSAmong 2636 women, 699 (26.5%) were found to be high-risk HPV positive. The highest infection rate (59.4%) was found in the age group of < or = 20 years and the lowest infection rate in the age group of 41 approximately 50 years (21.0%). Significant differences in HPV infection rate were found between different cities in Guangdong province, such as those between Xinhui and Guangzhou, Xinhui and Shenzhen, Xinhui and Dongguan (P < 0.01). Fifteen out of 16 women (93.8%) with cervical carcinoma were infected with high-risk HPV versus 24 out of 125 women (19.2%) attending routine cervical cancer screening (P < 0.001). The HPV infection rate was 30.8% (142 out of 461) in women with cervical erosion, which was significantly lower than that in patients with cervical carcinoma (P < 0.001). HPV DNA were detected in 100% (2/2) of squamous cell carcinoma (SCC), 100% (12/12) high grade squamous intraepithelial lesion (HSIL), 88.9% (16/18) of low grade squamous intraepithelial lesion (LSIL) and 37.8% (28/74) of atypical squamous cells (ASC).

CONCLUSIONHigh-risk HPV genotypes are the major causes of cervical cancers and HPV detection is a reliable adjuvant tool for cervical cancer screening.

Carcinoma, Squamous Cell ; epidemiology ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; epidemiology ; pathology ; virology ; Cervix Uteri ; pathology ; virology ; China ; epidemiology ; Female ; Human papillomavirus 16 ; isolation & purification ; Human papillomavirus 18 ; isolation & purification ; Humans ; Mass Screening ; Papanicolaou Test ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; epidemiology ; pathology ; Risk Factors ; Uterine Cervical Neoplasms ; epidemiology ; pathology ; virology ; Vaginal Smears

OBJECTIVETo study the feasibility of diagnosing of human papillomavirus (HPV) infection in paraffin-embedded cervical tissues by high-throughput gene chip technology and its clinical significance.

METHODSForty cases of HPV-related cervical lesions, including 18 cases of invasive squamous cell carcinoma, 12 cases of cervical intraepithelial neoplasia (CIN) III, 6 cases of CIN II and 4 cases of CIN I, were enrolled. DNA was extracted from paraffin-embedded tissues and amplified by polymerase chain reaction (PCR) using HPV DNA primers. The PCR products were then reversely hybridized with gene chip technology. The results were compared with that of in-situ hybridization (ISH).

RESULTSAll of the 18 cases of cervical squamous cell carcinoma were positive for high-risk HPV genotypes (with 1 case showing a mixture with low-risk genotypes). In contrast, 11 cases (91.7%) of CIN III, 5 cases (83%) of CIN II and none of the CIN I cases were positive for high-risk HPV genotypes. On the other hand, low-risk HPV genotypes were detected only in 1 case (17%) of CIN II and 2 cases (50%) of CIN I. The difference between the two groups (CIN III/squamous cell carcinoma versus CIN I/CIN II) was statistically significant (U = 80.0, P < 0.01). Among the 10 squamous carcinoma cases positive for HPV types 16 and 18 by gene chip technology, high-risk HPV DNA was also detected in 6 of them when using in-situ hybridization.

CONCLUSIONSGene chip technology is able to detect multiple HPV genotypes in paraffin-embedded tissues with high sensitivity and specificity. The distinction between low and high-risk HPV genotypes is seemed useful in prevention and management of cervical cancer.

Alphapapillomavirus ; genetics ; Carcinoma, Squamous Cell ; virology ; Cervical Intraepithelial Neoplasia ; diagnosis ; virology ; Cervix Uteri ; pathology ; virology ; DNA, Viral ; analysis ; Female ; Genotype ; Human papillomavirus 16 ; genetics ; Human papillomavirus 18 ; genetics ; Humans ; Oligonucleotide Array Sequence Analysis ; methods ; Papillomavirus Infections ; diagnosis ; virology ; Paraffin Embedding ; Polymerase Chain Reaction ; methods ; Uterine Cervical Neoplasms ; diagnosis ; virology