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

OBJECTIVE: DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. METHODS: A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. RESULTS: Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). CONCLUSION: DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.
Alphapapillomavirus/genetics ; *Atypical Squamous Cells of the Cervix/pathology/virology ; Cell Adhesion Molecules/genetics ; *DNA Methylation ; Female ; Genotype ; Humans ; Immunoglobulins/genetics ; Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics ; Paired Box Transcription Factors/genetics ; Papanicolaou Test ; Pituitary Adenylate Cyclase-Activating Polypeptide/genetics ; ROC Curve ; Squamous Intraepithelial Lesions of the Cervix/*genetics/pathology/virology ; Uterine Cervical Neoplasms/*genetics/pathology/virology ; Vaginal Smears

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

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 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

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

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

OBJECTIVETo confirm the relations between the expression of cyclin E, p16ink4, ki67 and HPV16/18 infection using cervical exfoliated cells, and evaluate the usefulness of cyclin E, p16ink4 and ki67 as biomarkers for screening of cervical carcinomas.

METHODSThe expression of cyclin E, p16ink4 oncoproteins and ki67 proliferative activity was evaluated immunohistochemically in 78 cervical exfoliated epithelial specimens. Human papillomavirus type16 and 18 (HPV16/18) infection was assessed by polymerase chain reaction (PCR) using type specific primers.

RESULTSCyclin E, p16ink4 and ki67 were all overexpressed in cervical preneoplasia and neoplasia cells, compared with little expressed in ASCUS (P less than 0.005). Overexpression of cyclin E was observed in CIN, (P less than 0.01), p16ink4 and ki67 overexpressed in invasive carcinoma(100 percent and 90.9 percent respectively). The degree of p16ink4 and ki67 expression correlated well with the degree of cervical neoplasia (P less than 0.005). HPV16 infection was assessed at all stages of cervical neoplasia samples, and a significant relationship with the degree of cervical epithelial lession was observed at the same time. The expression level of p16ink4 and ki67 seemed to be more closely associated with HPV16 infection than cyclin E did (rs=1.0 vs rs=0.4). HPV18 was found positive in only 1 case in CIN1 and in 4 cases in CIN2-3. Therefore no significance was found on statistical analysis (P less than 0.005).

CONCLUSIONCyclin E, p16ink4 and ki67 should be regarded as useful biomarkers of HPV-related cervical neoplasias, and be used for screening patients at high risk for developing cervical carcinomas. Moreover, cyclin E might be a significant cytologic marker for the primary screening of cervical carcinomas.

Adult ; Aged ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; virology ; Cervix Uteri ; cytology ; metabolism ; virology ; Cyclin E ; biosynthesis ; Cyclin-Dependent Kinase Inhibitor p16 ; biosynthesis ; DNA, Viral ; genetics ; Female ; Host-Pathogen Interactions ; Human papillomavirus 16 ; genetics ; physiology ; Human papillomavirus 18 ; genetics ; physiology ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; biosynthesis ; Middle Aged ; Papillomavirus Infections ; metabolism ; pathology ; virology ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms ; metabolism ; pathology

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

The ability of viral oncoproteins to subvert cell cycle checkpoints may constitute a mechanism by which viral oncoproteins induce genetic instability. HPV 16 E6 and E7 disrupt cell cycle checkpoints, particularly affecting nearly all cyclin-dependent kinase inhibitors linked to the G1- and G2- checkpoints, in each case by means of a different mechanism. HPV 16 E7 shows homology with the pRb binding sites of cyclin D1, which consequently releases E2F. In addition, E7 directly binds to p21, and releases PCNA and other S-phase promoting genes. In turn, released E2F activates cyclin E, and cyclin E accelerates p27 proteolysis as a function of the antagonistic reaction of its own inhibitor. The induction of p16 expression is assumed to be indirectly associated with E7, which is upregulated only after prolonged inactivation of Rb. HPV 16 E6 decreased the fidelity of multiple checkpoints controlling both entry into and exit from mitosis, with the mechanism of p53 inactivation. In addition, HPV 16 E6 increased the sensitivity to chemically induced S-phase premature mitosis and decreased mitotic spindle assembly checkpoint function. Alongside the impressive advances made in the understanding of the molecular mechanisms, which HPV disrupts, the validity of these conclusions should be evaluated in the diagnostic and prognostic fields.
Cervix Neoplasms/*pathology/virology ; Cyclin-Dependent Kinases/*antagonists & inhibitors ; Cyclins/analysis ; Female ; *G1 Phase ; *G2 Phase ; Human ; Microfilament Proteins/analysis ; Papillomavirus Infections/*pathology ; *Papillomavirus, Human ; Proliferating Cell Nuclear Antigen/analysis ; Protein p16/analysis ; Tumor Virus Infections/*pathology