OBJECTIVETo detect the high-risk human papillomavirus (HPV) infectious condition in women with abnormal cytology and evaluate its values in the screening of high grade squamous intraepithelial lesion.

METHODSWe used hybrid capture 2 (hc2) method to examine 949 patients with abnormal cervical cytology results [ > or =atypical squamous cells of undetermined significance (ASC-US) according to the 2001 The Bethesda System diagnosis criteria]. All subjects also received colposcopy for tissue studies.

RESULTSAmong 949 patients with abnormal cytology, the diagnoses of atypical squamous cells (ASC), low grade squamous intraepithelial lesion (LSIL), and high grade squamous intraepithelial lesion (HSIL) were made in 432, 310, and 207 patients, respectively. The high-risk HPV positive rate in ASC, LSIL, and HSIL were 40.3%, 44.8%, and 89.4%, respectively. The numbers of patients with pathologically confirmed results of negative intraepithelial lesion or malignancy (NILM), cervical intraepithelial neoplasia 1, 2, 3 (CIN 1, 2, 3), and squamous cell carcinoma (SCC) were 335, 388, 118, 101, and 7, and the high-risk HPV positive rate was 17.3%, 66.2%, 92.4%, 97.0%, and 100%, respectively. Among patients with atypical squamous cells of undetermined significance (ASC-US), rate of HSIL in high-risk HPV positive group and negative group were 10.2% and 0.8%, respectively (P < 0.01). In screening HSIL, the sensitivities of cytology [ > or = ASC cannot exclude HSIL (ASC-H)] and cytology ( > or = ASC-H) plus high-risk HPV testing were 0.925 and 0.991, and the specificities were 0.510 and 0.748, respectively (P < 0.01). Sensitivitives of cytology ( > or = LSIL) and cytology (> or = LSIL) plus high risk HPV in detecting HSIL were 0.898 and 0.982, respectively, while the specificitives were 0. 567 and 0.779, respectively (P < 0.01).

CONCLUSIONSThe positive rate of high-risk HPV increases with the gravity of cervical lesions. In patients with abnormal cervical cytology, high-risk HPV testing can improve the sensitivity and specificity in the screening of HSIL.

Carcinoma, Squamous Cell ; diagnosis ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; diagnosis ; pathology ; virology ; Female ; Humans ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; diagnosis ; pathology ; virology ; Risk Assessment ; Uterine Cervical Neoplasms ; diagnosis ; pathology ; virology

OBJECTIVETo investigate the correlation between the presence of human papillomavirus (HPV) DNA in the lymph nodes and histopathologically confirmed metastasis of early-stage cervical carcinoma.

METHODSHPV L1 gene fragment in paraffin-embedded tissue specimens of the primary tumor and pelvic lymph nodes from 31 patients with cervical cancer was amplified using HPV-specific PCR with general consensus primers GP5+/GP6+. The type of HPV was identified by sequence analysis of the PCR products, and the correlation between the presence of HPV DNA in the lymph node and the clinicopathological indices of cervical carcinoma was analyzed.

RESULTSThe positivity rate of HPV DNA in the pelvic lymph nodes was 58.1% in the 31 patients, and in 13 of the patients with confirmed metastasis, the detection rate was 84.6% as compared with the rate of 27.8% in the other 18 patients without metastases. The presence of HPV DNA in the lymph node was associated with histologically confirmed metastases. The results of both HPV DNA detection and pathological examination indicated that the obturator, internal iliac and external iliac lymph nodes were more liable to be positive for HPV DNA, accounting for over 90% of the positivity.

CONCLUSIONHPV DNA detection in the pelvic lymph nodes is a helpful predictive factor of metastases, and the obturator, internal iliac and external iliac lymph nodes are the among the most vulnerable lymph nodes of metastatic involvement by early-stage cervical carcinoma.

Adult ; DNA, Viral ; analysis ; genetics ; Female ; Host-Pathogen Interactions ; Humans ; Lymph Nodes ; pathology ; virology ; Lymphatic Metastasis ; Middle Aged ; Papillomaviridae ; genetics ; physiology ; Papillomavirus Infections ; pathology ; virology ; Polymerase Chain Reaction ; Tumor Virus Infections ; pathology ; virology ; Uterine Cervical Neoplasms ; pathology ; virology

OBJECTIVEThis study was designed to determine the prevalence of oncogenic human papillomavirus (HPV) in cervical infections in Beijing, China, and to investigate the odds ratio (OR) of HPV single and multiple infections in abnormal cytology.

METHODSA total of 19,018 specimens from outpatients in the department of obstetric and gynecology were collected. They were detected using high-risk HPV genotyping real-time polymerase chain reaction (PCR) kit and analyzed by ThinPrep cytology test for cervical pathological diagnosis. HPV prevalence, age-specific prevalence, and OR of each type of HPV in abnormal cytology were analyzed.

RESULTSOverall, 19.1% (3,623/19,018) of the individuals were positive for HPV infection, 14.9% (2,833/19,018) were positive for a single HPV type, and 4.2% (790/19,018) were positive for multiple types. Among the 3,623 HPV-positive individuals, the most predominant HPV types were HPV52 (4.4%, 834/19,018), HPV16 (3.7%, 710/19,018), and HPV58 (3.4%, 644/19,018). The OR of multiple infections and single infection differed significantly among disease severities. The OR of dual infection was higher than that of each of the two single infection types, respectively.

CONCLUSIONHPV prevalence in the outpatients was 19.1%, and the most predominant HPV types in the study were HPV52, HPV16, and HPV58. Women with multiple infectionswere more likely to have abnormal cytology.

Adolescent ; Adult ; Aged ; Beijing ; Female ; Genotype ; Humans ; Middle Aged ; Papillomaviridae ; classification ; genetics ; isolation & purification ; Papillomavirus Infections ; pathology ; virology ; Uterine Cervical Neoplasms ; pathology ; virology ; Young Adult

OBJECTIVETo study the relationship between thinprep cytologic test and the types of human papilloma virus (HPV) infection in cervical precancerous lesion screening.

METHODSTo perform high-risk HPV types test in 1375 samples. Choose 256 positive samples to take thinprep cytologic test (TCT) and directed biopsies under colposcopy. Adopting two-channels real time PCR to genotype and quantify eight high risk HPV DNA (high risk types: HPV 16, 18, 45, 31; intermediate risk types: HPV 33, 52, 58, 67).

RESULTSThere are 256 positive samples in High risk HPV DNA test (18.62%). WNL rate for TCT is 16.41% (42/256), ASCUS and above rate for TCT is 83.59% (214/256). There is no statistically significant difference in the viral loads of HPV infection rate between the TCT negative patients and positive patients (P > 0.5). Positive correspondence rate for TCT and biopsy are 92.86% (39/42), 81.36% (48/59), 85.19% (23/27) and 9/10.

CONCLUSIONHigh-risk HPV types checking combined with TCT and biopsy can raise positive rate significantly. It should be used as a reliable method for early diagnosis in cervical cancer and CIN screening.

Alphapapillomavirus ; classification ; genetics ; isolation & purification ; Cytodiagnosis ; methods ; Early Detection of Cancer ; methods ; Female ; Humans ; Papillomavirus Infections ; diagnosis ; pathology ; virology ; Uterine Cervical Neoplasms ; diagnosis ; pathology ; virology

Carcinoembryonic Antigen ; metabolism ; Carcinoma in Situ ; immunology ; pathology ; virology ; Carcinoma, Ductal, Breast ; immunology ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; immunology ; pathology ; virology ; DNA, Viral ; analysis ; Diagnosis, Differential ; Female ; Human papillomavirus 16 ; genetics ; isolation & purification ; Humans ; Ki-67 Antigen ; metabolism ; Uterine Cervical Dysplasia ; immunology ; pathology ; virology ; Uterine Cervical Neoplasms ; immunology ; pathology ; virology

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 disscuss different outcomes of ASC-UC and ASC-H, two subtypes of ASC, and the significance of HPV-DNA genotyping assays in these two subtypes.

METHODSWe reviewed and analyzed colposcopic and biopsy results of 1256 cases of ASC between Jan. 2005 to Dec. 2007, of which 580 cases have results of HPV-DNA genotyping assays.

RESULTSIn 1256 ASC cases, ASC-US and ASC-H cases account for 90.1% and 9.9% respectively, CIN2 and higher levels diagnosed via colposcopy and cervical biopsy are 8.5% and 24.2% respectively (P = 0.000). In ASC-US cases, the infection rate of HPV-DNA high risk types is 67.2%, there is statistic significance among different HPV-DNA results and biopsy pathology (P = 0.000). In ASC-H cases, the infection rate of HPV-DNA high risk types is 47.3%, there is no statistic significance among them (P = 0.054).

CONCLUSIONThe clinical outcomes of ASC-US and ASC-H are different, we should distinguish and treat. HPV-DNA genotyping assay is available in ASC-US triage, but Colposcopy is proposed for all ASC-H patients.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alphapapillomavirus ; genetics ; isolation & purification ; Female ; Genotype ; Humans ; Middle Aged ; Neoplasms, Squamous Cell ; pathology ; virology ; Papillomavirus Infections ; pathology ; virology ; Uterine Cervical Neoplasms ; pathology ; virology ; Young Adult

OBJECTIVE: To investigate the effect of human papillomavirus types 16E6 on the sensitivity of chemotherapy for cervical carcinoma in different p53 genotype cell lines. METHODS: The apoptosis rates of each group were detected by AO/EB, immunofluorescence and Annexin V/PI stained methods. The expressions of protein HPV16E6 and p53(mt) after the treatments of different concentration of DDP were detected by Western blot. HPV16E6 mRNA in C33A, C33A-E6, C33A-P, and CaSki cell lines under different DDP treatments were detected by RT-PCR. RESULTS: AO/EB and Annexin V/PI stained tests showed that the apoptosis rates of C33A, C33A-E6, C33A-P, and CaSki cells were significantly increased when DDP concentration increased. Western blot showed that the HPV16E6 protein could be detected only in C33A-E6 and CaSki cell lines. The expression of HPV16E6 protein in C33A-E6 and CaSki cell lines gradually decreased and was hardly detected with increased dosage of DDP and the prolonged treatment time (P<0.01), and slightly increased in C33A-E6 and Caski cell lines without the treatment, but there was no significant difference between them (P>0.05). Protein p53(mt) persistently expressed in C33A-E6, C33A, and C33A-P cell lines following the increased dosage of DDP and the prolonged treatment time(P>0.05), while it couldn't be found in CaSki cell line. RT-PCR showed that without DDP intervention, there was no significant difference of HPV16E6 mRNA in C33A-E6 and CaSki cell lines within 24 h.The HPV16E6 mRNA in C33A-E6 cell line expressed much higher than that in CaSki (P<0.05), and HPV16E6 mRNA of 2 cell lines expressed much higher at 48 h than at 24 h (P<0.05).The expression of HPV16E6 mRNA in C33A-E6 and CaSki cell lines gradually decreased with the increased DDP and prolonged treatment time (P<0.01), while there was no significant difference between C33A-E6 and CaSki cell lines under the same DDP concentration (P>0.05). CONCLUSION Effect of HPV16E6 on the sensitivity of chemotherapy for cervical carcinoma cell lines is not markedly related with the different p53 genotype forms(p53(mt)/p53wt ). HPV16E6 may affect the proliferation and sensitivity of chemotherapy in C33A cell line through other mechanism.
Antineoplastic Agents ; pharmacology ; Apoptosis ; genetics ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Female ; Genotype ; Human papillomavirus 16 ; genetics ; Humans ; Oncogene Proteins, Viral ; biosynthesis ; genetics ; Papillomavirus Infections ; virology ; Repressor Proteins ; biosynthesis ; genetics ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics ; Uterine Cervical Neoplasms ; pathology ; virology

OBJECTIVETo investigate the association between HPV16 infection, E6/E7 variations and the cervical lesions.

METHODSHPV subtypes were detected by using flow-through hybridization technique, E6/E7 gene was extracted from cervical lesions in 80 patients with HPV16 infection, PCR amplified, cloned into plasmid pMD18-T and sequenced.

RESULTSHPV 16 was the most common type which accounted for 33.3% (154/463), the HPV16 infection rates increased with the severity of cervical lesions (P < 0.05). Totally in 72 cases the complete E6 and E7 regions were successfully sequenced, the DNA mutation rate of E6/E7 was 88.9% (64/72). A mutation, E6-D32E (T96G) coincided with a specific type of E7 mutation, N29S (A86G). D32E/N29S mutation rate was 38.9% (28/72), the detection rate increased with the severity of cervical lesions (P < 0.05).

CONCLUSIONHPV 16 was the most common type in women with cervical lesions in Beijing, D32E/N29S variant associated with the cervical lesions.

Adult ; Aged ; China ; epidemiology ; Female ; Gene Frequency ; Genotype ; Host-Pathogen Interactions ; Human papillomavirus 16 ; genetics ; physiology ; Humans ; Middle Aged ; Mutation ; Oncogene Proteins, Viral ; genetics ; Papillomavirus E7 Proteins ; Papillomavirus Infections ; epidemiology ; pathology ; virology ; Repressor Proteins ; genetics ; Severity of Illness Index ; Uterine Cervical Diseases ; epidemiology ; pathology ; virology ; Uterine Cervical Neoplasms ; epidemiology ; pathology ; virology ; Young Adult

Prevention of infection by the human papillomavirus (HPV) has become a hot research topic since the relationship between the HPV and cervical cancer was confirmed. Persistent infection with HPV and early expression of proteins has an important role in the pathogenesis of cervical cancer. Vaccines that protect against four high-risk types of HPV (-6, -11, -16, -18) have been used worldwide. A bivalent vaccine (HPV-16 and -18) developed by Walvax is in clinical trials. This study reviews progress in ascertainment of the structure and function of the HPV genome, the molecular mechanism of carcinogenesis, and vaccines based on virus-like particles.
Animals ; Carcinogenesis ; Female ; Humans ; Papillomaviridae ; genetics ; immunology ; metabolism ; Papillomavirus Infections ; pathology ; prevention & control ; virology ; Papillomavirus Vaccines ; genetics ; immunology ; Uterine Cervical Neoplasms ; pathology ; prevention & control ; virology ; Viral Proteins ; genetics ; immunology ; metabolism