The special primers Of p53 exon 7 as wed as HPV16 E6 and E7 ORFs (Opening Rending Frame) were used with PCR, PCR-SSCP technique, and 35 specimens of cervical carcinoma were examined. The results were as follows: ① H...The special primers Of p53 exon 7 as wed as HPV16 E6 and E7 ORFs (Opening Rending Frame) were used with PCR, PCR-SSCP technique, and 35 specimens of cervical carcinoma were examined. The results were as follows: ① HPV16 E6, E7 DNA was found in 25/35 specimens (71. 4%),which proved again HPV16 Infection an important event in cervical carcinogenesis. However only 11/35 (31.42% ) bad E6 and E7 ORFs simultaneously, 3/35 (8. 57%) and 11/35 (31. 42% ) had only E6 or E7 respectively. ② No mutation and LOH (Loss of Heterozygote) of p53 exon 7 were found in allof 35 specimens. Additionally in the present study, we developed a non-isotopic PCR-SSCP method.展开更多
Accurate typing of the different human papillomavirus types is csscntial in view of the differ-ent pathological potential of the common virus types of human papillomavirus （HPV） present in thecervix. We have develop...Accurate typing of the different human papillomavirus types is csscntial in view of the differ-ent pathological potential of the common virus types of human papillomavirus （HPV） present in thecervix. We have developed hybridization, washing and autoradiography conditions that minimize thecross-hybridization among different specific types of HPV so as to allow clear - cut type assignmentthrough practical dot blot hybridization technique using nylon membrane and <sup>35</sup>S - labeled HPV - 16DNA probe. Under these conditions seventeen of thirty （56.7%） of squamous cell carcinomas of thecervix uteri obtained from Tianjin women were detected in the presence of HPV - 16 DNA.展开更多
Objective To evaluate the overexpression of cyclin G1 in cervical intraepithelial neoplasia （CIN） and cervical carcinoma, and the correlation between cyclin G1 and high-risk human papilloma virus （HPV） infection. ...Objective To evaluate the overexpression of cyclin G1 in cervical intraepithelial neoplasia （CIN） and cervical carcinoma, and the correlation between cyclin G1 and high-risk human papilloma virus （HPV） infection. Methods All of the specimens were obtained from the Department of Pathology of China-Japan Friendship Hospital from January 2000 to August 2004. We detected the expression of cyclin G1 with immunohistochemistry, HPV16/18 infection with in situ hybridization, and high-risk HPV infection with Hybrid capture system Ⅱ （HC-Ⅱ） in normal group （25 cases）, CIN Ⅰ （48 cases）, CIN Ⅱ （56 cases）, CIN Ⅲ（54 cases）, and invasive cervical squamous-cell carcinoma （SCC, 31 cases）. Results The positive rates of cyclin G1 expression in CIN（77.85% ）and SCC cervical tissues （87. 10% ） were significantly higher than normal （ 8.00%, P 〈 0. 01 ）, and the intensities of cyclin G1 expression in CIN（40. 60% ） and SCC cervical tissues （61.51%） were significantly higher than normal （2. 72%, P 〈0.05）. The positive rates and intensities of cyclin G1 expression increased gradually with the grade of cervical lesions. High-risk HPV infection rates were higher in CIN and SCC than normal groups （P 〈 0.05 ）. There was a positive correlation between cyclin G1 expression and high-risk HPV infection detected with HC-Ⅱ （Kendall＇s tau-b =0. 316, 0. 269, 0. 352, and 0. 474 in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ, and SCC, respectively, P 〈 0. 05 ）. Conclusions Cyclin G1 is overexpressed in CIN and SCC. Cyclin G1 may be a biomarker for detecting CIN and SCC. Cyclin G1 may play an important role in the oncogenesis of CIN and SCC by high-risk HPV infection.展开更多
AIM： To look for the evidence of human papilloma virus （HPV） infection in esophageal squamous cell carcinomas （ESCC） and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of ...AIM： To look for the evidence of human papilloma virus （HPV） infection in esophageal squamous cell carcinomas （ESCC） and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of esophageal carcinomas in Henan emigrants. METHODS： Papilloma virus （PV） and HPV were determined by UltrasensiveTM S-P immunohistochemistry （IHC） and in situ hybridization （ISH） in esophageal carcinoma tissues （82 cases） and the normal mucosa （40 cases）. RESULTS： IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV （16/18-E6） positive rate was 45.0%, 36.36%, 37.5%, respectively in esophageal carcinoma tissue specimens from Henan emigrants,the local citizens and patients in Hubei Cancer Hospital. The PV and HPV （16/18-E6） were negative in all normal esophageal mucosa specimens. No correlation was found between HPV in esophageal squamous cell carcinoma tissues and in grade 1-3 esophageal squamous cell carcinoma cells. In situ hybridization showed that the HPV （16/18） DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens. The positive rate of HPV （16/18） DNA in the esophageal carcinoma specimens was significantly higher than that in normal mucosa specimens （P〈0.05）. The positive rate was not different among the 3 groups of esophageal carcinoma tissue specimens （P〉0.05）.CONCLUSION： HPV infection is high in esophageal carcinoma of Henan emigrants, local residents and patients in Hubei Cancer Hospital. HPV is closely related with esophageal squarnous cell carcinoma. HPV infection may play an important role in esophageal squarnous cell carcinoma.展开更多
Objective: To investigate the prognostic value of pretreatment human papillomavirus(HPV) viral load for cervical cancer, and to develop nomograms based on HPV load and other clinicopathological factors for long-term s...Objective: To investigate the prognostic value of pretreatment human papillomavirus(HPV) viral load for cervical cancer, and to develop nomograms based on HPV load and other clinicopathological factors for long-term survival.Methods: We conducted a prospective study on cervical squamous cell carcinoma(SCC) patients diagnosed between January 2003 and December 2008. Cervical samples were tested for HPV viral load by the Hybrid Capture II(HCII) assay before treatment and 6 months after treatment. Clinical characteristics and follow-up information were also collected. A multivariable Cox proportional hazards model was used to adjust covariates in both the radical hysterectomy(RH) treatment group and concurrent chemoradiotherapy(CCRT) treatment group to identify relevant covariates, and then nomograms were constructed and used for internal validation.Results: A total of 520 SCC patients enrolled in this study with a median follow-up of 127 months, 360 patients received RH, whereas 160 patients received CCRT. The median HPV viral load in RH and CCRT groups was356.10 and 294.29, respectively. Tumor size was positively correlated with high pretreatment HPV load in both groups. In CCRT group, the advanced International Federation of Gynecology and Obstetrics(FIGO) stage and enlarged retroperitoneal lymph node status determined by computed tomography(LNSCT) were correlated with low HPV load group. Initial HPV viral load, FIGO stage and lymph node metastasis were prognostic factors for RH group, whereas HPV viral load, squamous cell carcinoma antigen(SCC-Ag) level and LNSCT were identified as prognostic factors for CCRT group. Nomograms incorporating these predictors for 10-year progression-free survival(PFS) were constructed [concordance index(C-index): 0.756, 0.749].Conclusions: A low pretreatment HPV viral load is an independent prognostic factor for poor prognosis of cervical SCC and is related to other clinicopathological factors. The survival nomogram based on HPV viral load could predict the long-term prognosis.展开更多
Viral infections contribute to approximately 12%of cancers worldwide,with the vast majority occurring in developing countries and areas.Two DNA viruses,Epstein-Barr virus(EBV) and human papillomavirus(HPV),are associa...Viral infections contribute to approximately 12%of cancers worldwide,with the vast majority occurring in developing countries and areas.Two DNA viruses,Epstein-Barr virus(EBV) and human papillomavirus(HPV),are associated with38%of all virus-associated cancers.The probability of one patient infected with these two distinct types of viruses is increasing.Here,we summarize the co-infection of EBV and HPV in human malignancies and address the possible mechanisms for the co-infection of EBV and HPV during tumorigenesis.展开更多
Objective： To explore the relationship between microsatellite alterations of RASSFIA gene and the development of cervical carcinoma, and its relationship with HPV16 infection. Methods： Two sites of microsatellite po...Objective： To explore the relationship between microsatellite alterations of RASSFIA gene and the development of cervical carcinoma, and its relationship with HPV16 infection. Methods： Two sites of microsatellite polymorphism of RASSFIA gene were selected. Polymerase chain reaction （PCR） technique was used to detect LOH and MSI in 50 cases of cervical carcinoma and 40 cases of cervical intraepithelial neoplasia （CIN）, and to detect the infection state of HPV16. Results： At D3S1478 and D3S4604, the LOH rates of cervical carcinomas were 32.6% （14/43） and 48.9% （23/47）, the MSI rates were 14% （6/43） and 19.1% （9/47）, respectively. The LOH rates of CINs were 31.4% （11/35） and 39.5% （15/38）, the MSI rates were 11.4% （4/35） and 15.8% （6/38）, respectively. There were no significant differences between cervical carcinomas and CINs in respect to their positive rates of LOH and MSI at D3S1478 and D3S4604 （P〉0.05）. There were significant differences in LOH rates at D3S1478 and D3S4604 between the stage Ⅰ-Ⅱ and Ⅲ-Ⅳ cervical carcinomas and between the well/moderately differentiated cervical carcinomas and the poorly differentiated cervical carcinomas （P〈0.05）. The positive rates of LOH and MSI for CIN Ⅲ and noninvasive cervical carcinomas were higher than those in CIN Ⅰ-Ⅱ. The rates of infection of HPV16 in cervical cancer was obviously higher than that in CIN and in normal cervical tissues （P〈0.05）, and the incidence of LOH of RASSFIA gene was higher in HPV16（＋） than that in HPV16（-） （P〈0.05）. Conclusion： The RASSFIA gene change is a relatively late event in cervical carcinomas. The detection of LOH and MSI of RASSFIA gene might be helpful to the early diagnosis and the screening of cervical carcinoma. It might also be useful for predicting the prognosis of cervical carcinoma.展开更多
Cases (n=44) with squamous cell cervical cancer (SCCA) and age-matched healthy controls (n=176) were analyzed. Significant difference due to human papillomavirus (HPV) infection, ages at the first marriage, ages at th...Cases (n=44) with squamous cell cervical cancer (SCCA) and age-matched healthy controls (n=176) were analyzed. Significant difference due to human papillomavirus (HPV) infection, ages at the first marriage, ages at the first sexual intercourse, ages at the first birth given to baby, number of gravidities, number of deliveries, Body Mass Index (BMI), education level of women and their husbands (p<0.05) was observed. According to multivariate logistic regression analysis, four factors have entered the model (p<0.05), including HPV infection [OR (odds ratio)=26.13, 95%CI (confidence interval)=9.40?72.60], education level of women (OR=0.41, 95%CI=0.21?0.79), education level of spouses (OR=0.45, 95%CI=0.22?0.94), BMI (OR=0.73, 95%CI=0.57?0.93). Moreover, HPV infection is relative to education level of women (r=?0.14), and their spouses (r=?0.21), age at the first marriage (r=?0.20), age at the first birth given to baby (r=?0.20) and BMI (r=?0.15).展开更多
Objective: The role of human papillomavirus (HPV) in the development of cervical carcinoma has been clearly established but other factors could be involved in cervical tumorigenesis such as loss of heterozygosity (LOH...Objective: The role of human papillomavirus (HPV) in the development of cervical carcinoma has been clearly established but other factors could be involved in cervical tumorigenesis such as loss of heterozygosity (LOH) and microsatellite instability (MI). The aim of the present study was to investigate the genetic instability in cervical carcinoma tissues and provide evidence for discovering new tumor suppressor genes and screening diagnostic molecular marker of cervical carcinoma. Methods: Fifty primary cervical carcinoma samples from high-incidence area were analyzed by PCR for HPV16 infection, LOH and microsatellite instability. Results: HPV16 was detected in 88% of the cases. Sixty-six percent of total cases showed LOH with no more than 3 different loci per case. The highest frequency of the allelic loss was found in D18S474 (18q21, 40.5%). MI was detected in 4 cases (8%) only. Conclusion: Different percentages of LOH on specific chromosomal regions were found and MI was very infrequent in cervical carcinoma. The putative suppressor gene(s) could be located on specific chromosome regions such as 18q, and genetic instability could be involved in cervical tumorigenesis.展开更多
To investigate the mutations in the upstream regulatory region (URR) of human papillomavirus type 16 (HPV-16) from the cervical cancer biopsies in Xinjiang Uygur women and its relationship to the high incidence of cer...To investigate the mutations in the upstream regulatory region (URR) of human papillomavirus type 16 (HPV-16) from the cervical cancer biopsies in Xinjiang Uygur women and its relationship to the high incidence of cervical cancer in the southern Xinjiang, the tissue DNA was extracted from the cervical cancer biopsies, and the URR segment of HPV-16 DNA was amplified, sequenced and analyzed. Thereafter, the polymorphism of URR in HPV-16 was then analyzed. It was demonstrated that the positive rate detected for the presence of URR in HPV-16 was 89.47% (17/19). Compared with the previously published sequence in URR of prototype HPV-16, some mutations were detected in the sequence of URR. The mutations in 17 URR fragments of HPV-16 could be divided into 11 patterns (XJU-1 to XJU-11) at nucleic acid level, in which each of XJU-1 and XJU-4 accounted for 23.53% (4/17), and other patterns of mutation accounted for 5.88% (1/17) . In comparison with the URR of prototype HPV-16, the DNA identity of these patterns was 98.50%-99.68% . In these 17 URR fragments, two point mutations occurred at position 7192 (G to T) and position 7520 (G to A) and they appeared to be constant in Xinjiang area. These two mutations were ubiquitous in the Asia-American type and conferred strong infection activity and carcinogenicity of this virus. In addition, the mutations at position 7729 (A to C), position 7843 (A to G) and position 7792 (C to T) could enhance its transcription activity considerably. It is concluded that some mutations occur in URR gene of HPV-16 in the cervical cancer biopsies taken from Uygur women in Xinjiang area, suggesting that certain relationship exists among the mutations in URR of HPV-16, the phylogeny of HPV-16 and the high incidence of cervical cancer in southern part of Xinjiang area.展开更多
Objectives: To evaluate the sensitivity and accuracy of the HPV DNA test in conjunction with thin prep cytology test as a screening method of human papillomavirus (HPV) infection. To study either the cervical erosion ...Objectives: To evaluate the sensitivity and accuracy of the HPV DNA test in conjunction with thin prep cytology test as a screening method of human papillomavirus (HPV) infection. To study either the cervical erosion is related to high risk HPV infection or to determine the mean age distribution that is more prone to HPV infection. Material and Methods: The study is a retrospective cohort implemented to determine the real performance of liquid based medium and HPV DNA testing combined in second clinical hospital of Jilin University Changchun, China. The study group included total 150 patients from January 1, 2011 to December 30, 2012. A computerized search identified patients with thin prep test results and high risk HPV DNA testing during a 2-year period was recruited. The patients were chosen after proper speculum examination followed by thin prep cytology (TCT) and HPV DNA test. Cytologic specimens were obtained with endocervical brush, which was rinsed into the vial of Cytyc. The residual samples after the cytology report were taken for reflex HPV DNA test. The manufacture protocol was followed for HPV DNA testing using Hybrid Capture II. Colposcopic biopsy was performed for the diagnosis purpose, in patients who had atypical squamous cells of undeter-mined significance (AUS-US), low grade intraepithelial lesion (LSIL) or high-grade intraepithelial lesion (HSIL) in cytology and with positive results of highrisk HPV DNA. The diagnostic criteria were based on the Bethesda System (TBS). Findings: The high risk HPV positive women with abnormal cytology had a CIN I risk of 73 (86%), whereas 35 (23.3%) high-risk HPV positive women out of 109 (72.7%) normal cytology who underwent histological biopsy had CIN I 16 (10.7%). The risk for cervical intraepithelial neoplasia (CIN) in women with high-risk HPV positive with normal cytology was higher among women invited for the first time 31 - 40 years of age 12 (8%) than among older women 1 (0.7%). Out of 44 (29.3%) women who had I degree erosion with 6 (14%) positive HPV DNA test 38 (86%) had a normal histology biopsy showing no statically significant between them. Conclusion: The data confirm that HR-HPV DNA testing is much more sensitive than cytology alone and that HPV DNA testing helps in identifying women with high risk of serious cervical disease in an efficient and medically acceptable manner. The other most significant advantage of this cervical cancer screening method is that women who are HPV DNA positive can easily and quickly referred for colposcopic examination (within one year), which could identify the precancerous and cancer stage. And those who are HPV DNA negative can safely have much longer screening intervals saving considerable costs. With mean age being 38 ± 10 years, age older than 30 years should undergo HPV DNA testing with cytology triage in primary screening. But in woman younger than 30 years using HPV DNA assay, as an initial screening step can increase the prevalence of abnormal smears and the positive predictive value of HPV followed by TCT. However, close follow-up is essential if the initial biopsy is negative because a considerable number of women may have HPV infection positive in subsequent studies.展开更多
Invasive stratified mucin-producing carcinoma(ISMC)is a recently described histologic variant of high-risk human papillomavirus(HPV)-associated endocervical adenocarcinoma,as the putative invasive counterpart of the s...Invasive stratified mucin-producing carcinoma(ISMC)is a recently described histologic variant of high-risk human papillomavirus(HPV)-associated endocervical adenocarcinoma,as the putative invasive counterpart of the stratified mucin-producing intraepithelial lesion(SMILE).ISMC can display variable architectural patterns and usually coexists with other more conventional types of HPV-associated carcinomas,which makes diagnosis and differential diagnosis of ISMC is difficult for pathologists.Moreover,the prognosis of ISMC is still controversial.We analyzed 6 ISMCs with detailed pathological and clinical information.Intraepithelial lesion,including 1 high-grade squamous intraepithelial lesion and 1 SMILE,was found.Various architectures were observed(including nest,glandular,solid,trabecular,and single cell).Nuclear peripheral palisading,apoptotic bodies and mitoses,and variable cytoplasmic mucin vacuoles were seen in all of our cases.The predominance of neutrophils infiltration was seen in only 1 tumor.All the tumors infiltrated the cervical stroma in Silva pattern C manner.p63 and/or p40 was characteristically expressed in the peripheral cells in only 2 cases.High-risk HPV infection was observed in 3/3 detected cases.All the patients were alive during the follow-up time.Recognition of this infrequent tumor may help pathologists and oncologists for an accurate diagnosis and a better understanding of the clinicopathological behavior.展开更多
文摘The special primers Of p53 exon 7 as wed as HPV16 E6 and E7 ORFs (Opening Rending Frame) were used with PCR, PCR-SSCP technique, and 35 specimens of cervical carcinoma were examined. The results were as follows: ① HPV16 E6, E7 DNA was found in 25/35 specimens (71. 4%),which proved again HPV16 Infection an important event in cervical carcinogenesis. However only 11/35 (31.42% ) bad E6 and E7 ORFs simultaneously, 3/35 (8. 57%) and 11/35 (31. 42% ) had only E6 or E7 respectively. ② No mutation and LOH (Loss of Heterozygote) of p53 exon 7 were found in allof 35 specimens. Additionally in the present study, we developed a non-isotopic PCR-SSCP method.
文摘Accurate typing of the different human papillomavirus types is csscntial in view of the differ-ent pathological potential of the common virus types of human papillomavirus （HPV） present in thecervix. We have developed hybridization, washing and autoradiography conditions that minimize thecross-hybridization among different specific types of HPV so as to allow clear - cut type assignmentthrough practical dot blot hybridization technique using nylon membrane and <sup>35</sup>S - labeled HPV - 16DNA probe. Under these conditions seventeen of thirty （56.7%） of squamous cell carcinomas of thecervix uteri obtained from Tianjin women were detected in the presence of HPV - 16 DNA.
文摘Objective To evaluate the overexpression of cyclin G1 in cervical intraepithelial neoplasia （CIN） and cervical carcinoma, and the correlation between cyclin G1 and high-risk human papilloma virus （HPV） infection. Methods All of the specimens were obtained from the Department of Pathology of China-Japan Friendship Hospital from January 2000 to August 2004. We detected the expression of cyclin G1 with immunohistochemistry, HPV16/18 infection with in situ hybridization, and high-risk HPV infection with Hybrid capture system Ⅱ （HC-Ⅱ） in normal group （25 cases）, CIN Ⅰ （48 cases）, CIN Ⅱ （56 cases）, CIN Ⅲ（54 cases）, and invasive cervical squamous-cell carcinoma （SCC, 31 cases）. Results The positive rates of cyclin G1 expression in CIN（77.85% ）and SCC cervical tissues （87. 10% ） were significantly higher than normal （ 8.00%, P 〈 0. 01 ）, and the intensities of cyclin G1 expression in CIN（40. 60% ） and SCC cervical tissues （61.51%） were significantly higher than normal （2. 72%, P 〈0.05）. The positive rates and intensities of cyclin G1 expression increased gradually with the grade of cervical lesions. High-risk HPV infection rates were higher in CIN and SCC than normal groups （P 〈 0.05 ）. There was a positive correlation between cyclin G1 expression and high-risk HPV infection detected with HC-Ⅱ （Kendall＇s tau-b =0. 316, 0. 269, 0. 352, and 0. 474 in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ, and SCC, respectively, P 〈 0. 05 ）. Conclusions Cyclin G1 is overexpressed in CIN and SCC. Cyclin G1 may be a biomarker for detecting CIN and SCC. Cyclin G1 may play an important role in the oncogenesis of CIN and SCC by high-risk HPV infection.
基金Supported by Key Technology R&D Program of Hubei Province, No.2004AA304B08
文摘AIM： To look for the evidence of human papilloma virus （HPV） infection in esophageal squamous cell carcinomas （ESCC） and to investigate the potential role and epidemiology of HPV infection in the pathogenesis of esophageal carcinomas in Henan emigrants. METHODS： Papilloma virus （PV） and HPV were determined by UltrasensiveTM S-P immunohistochemistry （IHC） and in situ hybridization （ISH） in esophageal carcinoma tissues （82 cases） and the normal mucosa （40 cases）. RESULTS： IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV （16/18-E6） positive rate was 45.0%, 36.36%, 37.5%, respectively in esophageal carcinoma tissue specimens from Henan emigrants,the local citizens and patients in Hubei Cancer Hospital. The PV and HPV （16/18-E6） were negative in all normal esophageal mucosa specimens. No correlation was found between HPV in esophageal squamous cell carcinoma tissues and in grade 1-3 esophageal squamous cell carcinoma cells. In situ hybridization showed that the HPV （16/18） DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens. The positive rate of HPV （16/18） DNA in the esophageal carcinoma specimens was significantly higher than that in normal mucosa specimens （P〈0.05）. The positive rate was not different among the 3 groups of esophageal carcinoma tissue specimens （P〉0.05）.CONCLUSION： HPV infection is high in esophageal carcinoma of Henan emigrants, local residents and patients in Hubei Cancer Hospital. HPV is closely related with esophageal squarnous cell carcinoma. HPV infection may play an important role in esophageal squarnous cell carcinoma.
基金supported by the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2016-I2M-1-001)
文摘Objective: To investigate the prognostic value of pretreatment human papillomavirus(HPV) viral load for cervical cancer, and to develop nomograms based on HPV load and other clinicopathological factors for long-term survival.Methods: We conducted a prospective study on cervical squamous cell carcinoma(SCC) patients diagnosed between January 2003 and December 2008. Cervical samples were tested for HPV viral load by the Hybrid Capture II(HCII) assay before treatment and 6 months after treatment. Clinical characteristics and follow-up information were also collected. A multivariable Cox proportional hazards model was used to adjust covariates in both the radical hysterectomy(RH) treatment group and concurrent chemoradiotherapy(CCRT) treatment group to identify relevant covariates, and then nomograms were constructed and used for internal validation.Results: A total of 520 SCC patients enrolled in this study with a median follow-up of 127 months, 360 patients received RH, whereas 160 patients received CCRT. The median HPV viral load in RH and CCRT groups was356.10 and 294.29, respectively. Tumor size was positively correlated with high pretreatment HPV load in both groups. In CCRT group, the advanced International Federation of Gynecology and Obstetrics(FIGO) stage and enlarged retroperitoneal lymph node status determined by computed tomography(LNSCT) were correlated with low HPV load group. Initial HPV viral load, FIGO stage and lymph node metastasis were prognostic factors for RH group, whereas HPV viral load, squamous cell carcinoma antigen(SCC-Ag) level and LNSCT were identified as prognostic factors for CCRT group. Nomograms incorporating these predictors for 10-year progression-free survival(PFS) were constructed [concordance index(C-index): 0.756, 0.749].Conclusions: A low pretreatment HPV viral load is an independent prognostic factor for poor prognosis of cervical SCC and is related to other clinicopathological factors. The survival nomogram based on HPV viral load could predict the long-term prognosis.
基金supported by the National Basic Research Program of China[2011CB504300(Y.T.Y.C.),2015CB553903(Y.T.)]+2 种基金the National High Technology Research and Development Program of China(863 Program)[2012AA02A501(Y.C.)]the National Natural Science Foundation of China[81,171,881 and81372427(Y.T.),81271763(S.L.),81,302,354(Y.S.)]the Hunan Natural Science Foundation of China[12JJ1013(Y.T.)]
文摘Viral infections contribute to approximately 12%of cancers worldwide,with the vast majority occurring in developing countries and areas.Two DNA viruses,Epstein-Barr virus(EBV) and human papillomavirus(HPV),are associated with38%of all virus-associated cancers.The probability of one patient infected with these two distinct types of viruses is increasing.Here,we summarize the co-infection of EBV and HPV in human malignancies and address the possible mechanisms for the co-infection of EBV and HPV during tumorigenesis.
文摘Objective： To explore the relationship between microsatellite alterations of RASSFIA gene and the development of cervical carcinoma, and its relationship with HPV16 infection. Methods： Two sites of microsatellite polymorphism of RASSFIA gene were selected. Polymerase chain reaction （PCR） technique was used to detect LOH and MSI in 50 cases of cervical carcinoma and 40 cases of cervical intraepithelial neoplasia （CIN）, and to detect the infection state of HPV16. Results： At D3S1478 and D3S4604, the LOH rates of cervical carcinomas were 32.6% （14/43） and 48.9% （23/47）, the MSI rates were 14% （6/43） and 19.1% （9/47）, respectively. The LOH rates of CINs were 31.4% （11/35） and 39.5% （15/38）, the MSI rates were 11.4% （4/35） and 15.8% （6/38）, respectively. There were no significant differences between cervical carcinomas and CINs in respect to their positive rates of LOH and MSI at D3S1478 and D3S4604 （P〉0.05）. There were significant differences in LOH rates at D3S1478 and D3S4604 between the stage Ⅰ-Ⅱ and Ⅲ-Ⅳ cervical carcinomas and between the well/moderately differentiated cervical carcinomas and the poorly differentiated cervical carcinomas （P〈0.05）. The positive rates of LOH and MSI for CIN Ⅲ and noninvasive cervical carcinomas were higher than those in CIN Ⅰ-Ⅱ. The rates of infection of HPV16 in cervical cancer was obviously higher than that in CIN and in normal cervical tissues （P〈0.05）, and the incidence of LOH of RASSFIA gene was higher in HPV16（＋） than that in HPV16（-） （P〈0.05）. Conclusion： The RASSFIA gene change is a relatively late event in cervical carcinomas. The detection of LOH and MSI of RASSFIA gene might be helpful to the early diagnosis and the screening of cervical carcinoma. It might also be useful for predicting the prognosis of cervical carcinoma.
文摘Cases (n=44) with squamous cell cervical cancer (SCCA) and age-matched healthy controls (n=176) were analyzed. Significant difference due to human papillomavirus (HPV) infection, ages at the first marriage, ages at the first sexual intercourse, ages at the first birth given to baby, number of gravidities, number of deliveries, Body Mass Index (BMI), education level of women and their husbands (p<0.05) was observed. According to multivariate logistic regression analysis, four factors have entered the model (p<0.05), including HPV infection [OR (odds ratio)=26.13, 95%CI (confidence interval)=9.40?72.60], education level of women (OR=0.41, 95%CI=0.21?0.79), education level of spouses (OR=0.45, 95%CI=0.22?0.94), BMI (OR=0.73, 95%CI=0.57?0.93). Moreover, HPV infection is relative to education level of women (r=?0.14), and their spouses (r=?0.21), age at the first marriage (r=?0.20), age at the first birth given to baby (r=?0.20) and BMI (r=?0.15).
基金This work was supported by the National Natural Science Foundation of China (No. 301710420).
文摘Objective: The role of human papillomavirus (HPV) in the development of cervical carcinoma has been clearly established but other factors could be involved in cervical tumorigenesis such as loss of heterozygosity (LOH) and microsatellite instability (MI). The aim of the present study was to investigate the genetic instability in cervical carcinoma tissues and provide evidence for discovering new tumor suppressor genes and screening diagnostic molecular marker of cervical carcinoma. Methods: Fifty primary cervical carcinoma samples from high-incidence area were analyzed by PCR for HPV16 infection, LOH and microsatellite instability. Results: HPV16 was detected in 88% of the cases. Sixty-six percent of total cases showed LOH with no more than 3 different loci per case. The highest frequency of the allelic loss was found in D18S474 (18q21, 40.5%). MI was detected in 4 cases (8%) only. Conclusion: Different percentages of LOH on specific chromosomal regions were found and MI was very infrequent in cervical carcinoma. The putative suppressor gene(s) could be located on specific chromosome regions such as 18q, and genetic instability could be involved in cervical tumorigenesis.
基金grants from the National Natural Science Foundation of China （No. 30460008） .
文摘To investigate the mutations in the upstream regulatory region (URR) of human papillomavirus type 16 (HPV-16) from the cervical cancer biopsies in Xinjiang Uygur women and its relationship to the high incidence of cervical cancer in the southern Xinjiang, the tissue DNA was extracted from the cervical cancer biopsies, and the URR segment of HPV-16 DNA was amplified, sequenced and analyzed. Thereafter, the polymorphism of URR in HPV-16 was then analyzed. It was demonstrated that the positive rate detected for the presence of URR in HPV-16 was 89.47% (17/19). Compared with the previously published sequence in URR of prototype HPV-16, some mutations were detected in the sequence of URR. The mutations in 17 URR fragments of HPV-16 could be divided into 11 patterns (XJU-1 to XJU-11) at nucleic acid level, in which each of XJU-1 and XJU-4 accounted for 23.53% (4/17), and other patterns of mutation accounted for 5.88% (1/17) . In comparison with the URR of prototype HPV-16, the DNA identity of these patterns was 98.50%-99.68% . In these 17 URR fragments, two point mutations occurred at position 7192 (G to T) and position 7520 (G to A) and they appeared to be constant in Xinjiang area. These two mutations were ubiquitous in the Asia-American type and conferred strong infection activity and carcinogenicity of this virus. In addition, the mutations at position 7729 (A to C), position 7843 (A to G) and position 7792 (C to T) could enhance its transcription activity considerably. It is concluded that some mutations occur in URR gene of HPV-16 in the cervical cancer biopsies taken from Uygur women in Xinjiang area, suggesting that certain relationship exists among the mutations in URR of HPV-16, the phylogeny of HPV-16 and the high incidence of cervical cancer in southern part of Xinjiang area.
文摘Objectives: To evaluate the sensitivity and accuracy of the HPV DNA test in conjunction with thin prep cytology test as a screening method of human papillomavirus (HPV) infection. To study either the cervical erosion is related to high risk HPV infection or to determine the mean age distribution that is more prone to HPV infection. Material and Methods: The study is a retrospective cohort implemented to determine the real performance of liquid based medium and HPV DNA testing combined in second clinical hospital of Jilin University Changchun, China. The study group included total 150 patients from January 1, 2011 to December 30, 2012. A computerized search identified patients with thin prep test results and high risk HPV DNA testing during a 2-year period was recruited. The patients were chosen after proper speculum examination followed by thin prep cytology (TCT) and HPV DNA test. Cytologic specimens were obtained with endocervical brush, which was rinsed into the vial of Cytyc. The residual samples after the cytology report were taken for reflex HPV DNA test. The manufacture protocol was followed for HPV DNA testing using Hybrid Capture II. Colposcopic biopsy was performed for the diagnosis purpose, in patients who had atypical squamous cells of undeter-mined significance (AUS-US), low grade intraepithelial lesion (LSIL) or high-grade intraepithelial lesion (HSIL) in cytology and with positive results of highrisk HPV DNA. The diagnostic criteria were based on the Bethesda System (TBS). Findings: The high risk HPV positive women with abnormal cytology had a CIN I risk of 73 (86%), whereas 35 (23.3%) high-risk HPV positive women out of 109 (72.7%) normal cytology who underwent histological biopsy had CIN I 16 (10.7%). The risk for cervical intraepithelial neoplasia (CIN) in women with high-risk HPV positive with normal cytology was higher among women invited for the first time 31 - 40 years of age 12 (8%) than among older women 1 (0.7%). Out of 44 (29.3%) women who had I degree erosion with 6 (14%) positive HPV DNA test 38 (86%) had a normal histology biopsy showing no statically significant between them. Conclusion: The data confirm that HR-HPV DNA testing is much more sensitive than cytology alone and that HPV DNA testing helps in identifying women with high risk of serious cervical disease in an efficient and medically acceptable manner. The other most significant advantage of this cervical cancer screening method is that women who are HPV DNA positive can easily and quickly referred for colposcopic examination (within one year), which could identify the precancerous and cancer stage. And those who are HPV DNA negative can safely have much longer screening intervals saving considerable costs. With mean age being 38 ± 10 years, age older than 30 years should undergo HPV DNA testing with cytology triage in primary screening. But in woman younger than 30 years using HPV DNA assay, as an initial screening step can increase the prevalence of abnormal smears and the positive predictive value of HPV followed by TCT. However, close follow-up is essential if the initial biopsy is negative because a considerable number of women may have HPV infection positive in subsequent studies.
基金the Scientific Research Funds Project of the Science and Technology Department of Sichuan Province(Grant No.21YYJC1616 to Liu Y).
文摘Invasive stratified mucin-producing carcinoma(ISMC)is a recently described histologic variant of high-risk human papillomavirus(HPV)-associated endocervical adenocarcinoma,as the putative invasive counterpart of the stratified mucin-producing intraepithelial lesion(SMILE).ISMC can display variable architectural patterns and usually coexists with other more conventional types of HPV-associated carcinomas,which makes diagnosis and differential diagnosis of ISMC is difficult for pathologists.Moreover,the prognosis of ISMC is still controversial.We analyzed 6 ISMCs with detailed pathological and clinical information.Intraepithelial lesion,including 1 high-grade squamous intraepithelial lesion and 1 SMILE,was found.Various architectures were observed(including nest,glandular,solid,trabecular,and single cell).Nuclear peripheral palisading,apoptotic bodies and mitoses,and variable cytoplasmic mucin vacuoles were seen in all of our cases.The predominance of neutrophils infiltration was seen in only 1 tumor.All the tumors infiltrated the cervical stroma in Silva pattern C manner.p63 and/or p40 was characteristically expressed in the peripheral cells in only 2 cases.High-risk HPV infection was observed in 3/3 detected cases.All the patients were alive during the follow-up time.Recognition of this infrequent tumor may help pathologists and oncologists for an accurate diagnosis and a better understanding of the clinicopathological behavior.
