Correlation between Physical Status of Human Papilloma Virus and Cervical Carcinogenesis

The prevalence of human papilloma virus (HPV)-16 in patients with cervical cancer,the physical status of HPV-16 in patients with cervical lesions,and the role of HPV-16 integration in cervi-cal carcinogenesis were investigated.HPV genotyping was performed by using PCR approach with the primer GP5+/GP6+ and type-specific primer on biopsy specimens taken operatively from 198 women.Multiple PCR was done to detect physical status of HPV-16 in a series of cervical liquid-based cytology samples and biopsy specimens obtained from different cervical lesions with HPV-16 infection,includ-ing 112 specimens with cervical cancer,151 specimens with CINⅠ,246 specimens with CINⅡ and 120 specimens with CINⅢ.The results showed that there were 112 cervical cancer samples (56.57% of total cervical cancer patients) with HPV-16 infection.The frequency of HPV-16 pure integration was 65.18% (73/112),56.57% (47/120),23.58% (58/246) and 7.95% (12/151) in cervical cancer,CINⅢ,CINⅡand CINⅠ patients respectively.In situ hybridization was performed on some paraffin-embedded sections of CINⅡ,CINⅢ and cervical cancer to verify the physical status of HPV-16 infection.Sig-nificant difference was observed between cervical cancer and CINⅠ,CINⅡ,CINⅢ in the frequency of HPV-16 integration (P<0.01).It is suggested that HPV-16 is the most prevalent type and is associated with cervical cancer.In the case of HPV-16 infection there are close associations between the severity of cervical lesions and the frequency of HPV-16 integration.The application of testing HPV genotyping and physical status based on detection of HC-Ⅱ HPV DNA would be in favor of predicting the progno-sis of cervical precancerosis and enhancing the screening accuracy of cervical cancer.

Detection of Human Papilloma Virus Type 16 E6 mRNA in Laryngeal Squamous Cell Carcinoma by In Situ Hybridization

Objective：Laryngeal squamous cell carcinoma（LSCC） is a common malignant tumor in Northeast China and is frequently associated with well-established risk factors like smoking and alcohol abuse.Human papilloma virus（HPV） is an epitheliotropic oncogenic virus that has been detected in a variety of head and neck tumors including LSCC.This retrospective study was to investigate the prevalence of HPV infection in patients with LSCC.Methods：In situ hybridization was performed in 99 patients with LSCC to detect the expression of HPV-16 E6 mRNA.Results：The positive rate of HPV16 E6 mRNA was 36.36%（36/99） in laryngeal squamous cell carcinoma（LSCC）,whereas only 3 of 50（6%） specimens of the normal laryngeal mucosa as a control group showed positive results（P0.05）.Additionally,there was no corelation between HPV16 and age,gender,clinical stage,nodal status and tumor site（P0.05）.Conclusion：The results suggest that the increased prevalence of HPV infection compared to normal laryngeal mucosa and the fact that high-risk HPV types（especially type 16） were the most frequently identified do not allow the exclusion of HPV as a risk factor in laryngeal squamous cell carcinoma.However,their clinical value remains to be further investigated.

Studies on the correlation between human papilloma virus vaccine and premature ovarian failure

Cervical cancer is the most common malignant tumour of the female reproductive system,resulting in more than 500,000 new cases annually worldwide.In developing countries,cervical cancer ranks second in terms of cancer mortality among women.Human papilloma virus is the primary causative agent of cervical cancer,with approximately 70 percent of cervical cancers caused by high-risk types of human papilloma virus 16 and 18.There are currently three types of human papilloma virus vaccines available:bivalent,quadri-valent and nine-valent.However,in recent years,it is reported that cervical cancer vaccine can cause premature ovarian failure.Consequently,an extensive literature search to find out the correlation between human papilloma virus vaccine and premature ovarian failure became a priority.There is no sufficient evidence to support or prove that there is a link between the human papilloma virus vaccine and premature ovarian failure.Hence,the vaccine does not cause premature ovarian failure.

Incidence of human papilloma virus in esophageal squamous cell carcinoma in patients from the Lublin region

AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.The controls were patients referred to our department due to other nonesophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology.In the ESCC patients,samples were taken from normal mucosa(56 mucosa samples) and from the tumor(56 tumor samples).Tissue samples from the controls were taken from normal mucosa of the middle esophagus(35 control samples).Quantitative determination of DNA was carried out using a spectrophotometric method.Genomic DNA was isolated using the QIAamp DNA Midi Kit.HPV infection was identified following PCR amplification of the HPV gene sequence,using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV.The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS:In tumor samples,HPV DNA was identified in 28 of 56 patients(50%).High risk HPV phenotypes(16 or/and 18) were found in 5 of 56 patients(8.9%),low risk in 19 of 56 patients(33.9%) and other types of HPV(37,81,97,CP6108) in 4 of 56 patients(7.1%).In mucosa samples,HPV DNA was isolated in 21 of 56 patients(37.5%).High risk HPV DNA was confirmed in 3 of 56 patients(5.3%),low risk HPV DNA in 12 of 56 patients(21.4%),and other types of HPV in 6 of 56 patients(10.7%).In control samples,HPV DNA was identified in 4 of 35 patients(11.4%) with no high risk HPV.The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56(50%) vs 4 of 35(11.4%),P < 0.001].In esophageal cancer patients,both in tumor and mucosa samples,the predominant HPV phenotypes were low risk HPV,isolated 4 times more frequently than high risk phenotypes [19 of 56(33.9%) vs 5 of 56(8.9%),P < 0.001].A higher prevalence of HPV was identified in female patients(71.4% vs 46.9%).Accordingly,the high risk phenotypes were isolated more frequently in female patients and this difference reached statistical significance [3 of 7(42.9%) vs 2 of 49(4.1%),P < 0.05].Of the pathological characteristics,only an infiltrative pattern of macroscopic tumor type significantly correlated with the presence of HPV DNA in ESCC samples [20 of 27(74.1%) vs 8 of 29(27.6%) for ulcerative or protruding macroscopic type,P < 0.05].The occurrence of total HPV DNA and both HPV high or low risk phenotypes did not significantly differ with regard to particular grades of cellular differentiation,phases in depth of tumor infiltration,grades of nodal involvement and stages of tumor progression.CONCLUSION:Low risk HPV phenotypes could be one of the co-activators or/and co-carcinogens in complex,progressive,multifactorial and multistep esophageal carcinogenesis.

Human papilloma virus 16 E6 oncoprotein associated with p53 inactivation in colorectal cancer

AIM:To investigate the association between human papilloma virus(HPV) infection and colorectal cancer.METHODS:Sixty-nine patients with pathologically confirmed primary colorectal cancer including 6 stage Ⅰ,24 stage Ⅱ,21 stage Ⅲ,and 18 stage Ⅳ patients were enrolled in this study to investigate whether HPV 16 could be involved in colorectal tumorigenesis.Nested-polymerase chain reaction(nested-PCR) was used to detect HPV16 DNA in colorectal tumor tissues and further confirmed by in situ hybridization(ISH).In addition,immunohistochemistry analysis was performed to examine the E6 oncoprotein in colorectal tumors.To verify whether E6 could inactivate the p53 transcriptional function,the levels of p21 and Mdm2 mRNA expression were evaluated by real-time reverse transcription(RT)-PCR.RESULTS:Of the 69 colorectal tumors,HPV16 DNA was detected in 11(16%) by nested-PCR,and HPV16 DNA was present in 8 of the 11(73%) tumors which was confirmed by ISH.The presence of HPV16 DNA in colorectal tumors was not associated with patients' clinical parameters including age,gender,smoking status,tumor site;however,HPV16 infection was more common in stage Ⅰ patients than in late-stages patients(Ⅱ,Ⅲ and Ⅳ).We next asked whether HPV16 infection could be linked with colorectal cancer development.Immunohistochemical data indicated that 8 of the 11 HPV16 DNA-positive tumors had E6 oncoprotein expression.Moreover,we also observed that the adjacent normal tissues including endothelial cells,lymphocytes,fibroblasts,and gland cells in E6-positive tumors had E6 oncoprotein expression.In addition,3 of the 4(75%) E6-positive tumors carrying p53 wild-type had negative immunostaining,but one tumor had less p53 immunostaining.We further examined whether E6-positive and/or p53 mutated tumors reduce p53 transcriptional activity.Real-time RT-PCR analysis indicated that p21 and mdm2 mRNA expression levels in E6/p53-wildtype tumors were significantly lower than in their adjacent normal tissues;as expected,E6-positive/p53-mutated tumors had lower p21 and mdm2 mRNA expression levels compared with their adjacent normal tissues.These results clearly indicate that the E6 oncoprotein expressed in p53 wildtype tumors may reduce p21 and mdm2 expression via p53 inactivation.CONCLUSION:These results suggest that HPV16 infection may be involved in a subset of colorectal cancer,and we suggest that the transmission of HPV to the colon and rectum might occur through peripheral blood lymphocytes.

Lymphocyte subsets predictive value and possible involvement of human papilloma virus infection on breast cancer molecular subtypes

AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed with breast cancer and 26 patients with benign pathology of the breast. Molecular subtype classification was performed based on the immunohistochemical reports of the tumor piece. HPV genome detection and genotyping from fresh breast biopsies was performed using the INNO-LIPA HPV Genotyping Extra test(Innogenetics, Ghent, Belgium). CD3+, CD4+, CD8+ and natural killer(NK)+ cells levels from peripheral blood samples from patients with breast cancer and benign pathology were measured by flow cytometry. RESULTS Luminal A was the most frequent breast cancer molecular subtype(33.33%). HPV was detected in 25% of the breast cancer patients, and genotype 18 was the most frequent in the studied population. The mean of CD3+, CD4+ and CD8+ subpopulations were decreased in patients with breast cancer, in relation to those with benign pathology, with a statistically significant difference in CD8+ values(P = 0.048). The mean of NK+ cells was increased in the benign pathology group. The average level of CD3+, CD4+, CD8+ and NK+ cells decreased as the disease progressed. HER2+ and Luminal B HER2+ tumors had the lowest counts of cell subsets. HPV breast cancer patients had elevated counts of cellular subsets. CONCLUSION Determining level changes in cellular subsets in breast cancer patients is a useful tool to evaluate treatment response.

Human papilloma virus and esophageal carcinoma in a Latin-American region

AIM:To investigate the presence of high-risk human papilloma virus (HPV) in esophageal squamous cell carcinomas (ESCCs) in a non-selected Mexican population.METHODS: Cases with a pathological diagnosis of squamous cell carcinoma of the esophagus were obtained from Department of Pathology files, at the National Cancer Institute in Mexico City during the period between 2000 and 2008. Slides from each case were reviewed and cases with sufficient neoplastic tissue were selected for molecular analysis. DNA was extracted from paraffin-embedded tissue samples for polymerase chain reaction analysis to detect HPV DNA sequences. Demographic and clinical data of each patient were retrieved from corresponding clinical records.RESULTS: HPV was detected in 15 (25%) of ESCCs. HPV-16 was the most frequently observed genotype, followed by HPV-18; HPV-59 was also detected in one case. Unfortunately, HPV genotype could not be established in three cases due to lack of material for direct sequencing, although universal primers detected the presence of HPV generic sequences. No low-risk HPV genotypes were found nor was HPV-16/18 co-infection. HPV presence in ESCC was not significantly associated with gender, age, alcohol consumption, smoking, anatomic location, or histologic grade. All patients belonged to low and very low socioeconomic strata, and were diagnosed at advanced disease stage. Male patients were most commonly affected and the male:female ratio in HPV-positive ESCC increased two- fold in comparison with HPV-negative cases (6.5:1 vs 3.1:1).CONCLUSION: High prevalence of high-risk HPV in ESCC in Mexico does not support the hypothesis that HPV-associated ESCC is more common in areas with higher ESCC incidence rates.

RELATIONSHIP BETWEEN CYCLIN G1 AND HUMAN PAPILLOMA VIRUS INFECTION IN CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CARCINOMA

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, CINII, 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.

Potential role of human papilloma virus in the pathogenesis of gastric cancer

AIM:To demonstrate the presence and biological activity of human papilloma virus(HPV)in gastric cancer(GAC)tissues.METHODS:The study involved 84 surgically treated patients with gastric adenocarcinoma,regardless of the clinical stage of the disease.The presence of HPV DNA of high oncogenic risk types in formalin-fixed,paraffinembedded tumor samples was determined using quantitative polymerase chain reaction analysis.A stringentprotocol of prevention of cross-and environmental contamination was applied during DNA isolation,and amplification,as well as confirmation of the biological activity of the virus in tumor cells,was implemented.The study utilized the Real-time High Risk HPV test,which detects the DNA of 14 HPV subtypes that are considered to have high oncogenic potential.The overexpression of the p16INK4a protein assessed immunohistochemically was considered confirmation of the HPV infection.RESULTS:Among the 89 patients initially included in the study group,diagnostic results were obtained for84 individuals.In five cases,either the histopathological material was too scant to isolate the necessary amount of DNA,or the isolated DNA was significantly degraded,resulting in the failure of internal control amplification within the predefined number of 35 cycles.Those patients were excluded from further analysis.The amplification of HPV DNA was demonstrated in none of the84 tissue samples;thus,all cases were considered to have a negative DNA status of highly oncogenic HPV subtypes.Immunohistochemical staining provided diagnostic results for all of the examined tissue samples,and excluded the accumulation of the p16INK4a protein in tumor cells,thus confirming the lack of active HPV infection in all of the individuals.CONCLUSION:The study does not confirm the presence or biological activity of HPV in tumor tissues.Thus,the relationship between GAC and HPV infection,in the Central European population seems doubtful.

Prevalence and Genotype Distribution of Oncogenic-Risk Human Papilloma Virus in the Cervix of Climacteric Women with Normal Pap Smears

Objective: To find out the incidence of high-risk HPV infections on climacteric women within our area of influence;and to typify HPV genotypes on women with normal cytology that come to our hospitalary unit of menopausia. Material and Method: Cross-sectional study;with a random sample of 140 cases of climacteric women of ≥50 years of age, with normal Pap smears for the last 12 months. HPV determination was carried out by PCR for screening, and by hybrid capture for genotype typification. Results: The percentage of climacteric women who are carriers of oncogenic HPV and a normal Pap smear was of 11.43% (16/140 cases). The genotype found most frequently was HPV-16, followed by HPV-58, 51 and 18. Conclusions: We found a high prevalence of women who were carriers of oncogenic HPV in climacteric women with normal Pap smears (latent infections) in our health region. We consider that cervical cancer screening, either by PCR or conventional Pap smear, should not be minimized or ignored from 50 years of age onwards.

COMPARISON BETWEEN IMMUNOFLUORESCENCE AND PCR IN DETECTING HUMAN PAPILLOMA VIRUS IN CONDYLOMA ACUMINATA

Objective To compare the effectiveness of immunofluorescence and polymerase chain reaction (PCR) in detecting human papilloma virus (HPV) in condyloma acuminata (CA). Methods HPVs in CA tissues from 60 patients were detected by immunofluorescence and PCR, respectively. Different subtypes of HPVs were also identified with restriction fragment length polymorphism (RFLP). Results The positive detective rates of immunofluorescence and PCR were 56.67% (34/60) and 96.67% (58/60), respectively (P<0.01). RFLP results showed HPV6 and HPV11 were the main subtypes in the detected virus, which accounted for 98.28%. Conclusion The sensibility of PCR is superior to that of immunofluorescence.

Smoking and genital human papilloma virus infection in women attending cervical cancer screening in Greece

AIM: To investigate whether smoking is associated with human papilloma virus(HPV) infection. METHODS: HPV infection is considered to be a neces-sary condition for cervical cancer development. The study population included 1291 women, aged 25-55 years, attending cervical cancer screening. All women had a Papanicolaou(Pap) test, with liquid-based cytology(Thinprep), an HPV-DNA test and an evaluation of smoking habits. The COBAS 4800 system was used for HPV-DNA testing, enabling identifi cation of the following high-risk HPV(hr HPV)-types: each of HPVs 16 and 18 separately, and HPVs 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 as a cocktail. The evaluation of smoking habits was assessed using the smoking intensity index(SII), a variable formed as the product of cigarettes consumed per day by the days(years × 365) that a woman was a smoker, divided by 1000. RESULTS: There were 136 smokers among 238 women tested positive for hr HPV-types(HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and/or 68), and 463 smokers among 1053 hr HPV-negative women(OR = 1.7, P < 0.001). This association was attributed to the youngest age group of women, aged 25-34 years(OR = 2.3, P < 0.001), while there was no association in other age groups. The intensity of smoking(increasing SII) showed no statistically signifi cant association with hr HPV infection. Cervical infection with HPV 16 and/or HPV 18 was also not associated with age or smoking habits. Finally, no association was found between Pap test status and smoking habits or smoking intensity. CONCLUSION: Smoking appears to be associated with hr HPV infection of the uterine cervix, particularly in younger women. Further studies should investigate whether this association is based on causality and evaluate the role of other possible co-factors.

Human papilloma virus vaccination: Review article and an update

Human papilloma virus(HPV) is sexually transmitted and associated with uterine cervix, vaginal, and vulvar cancers in females, oropharyngeal and anal cancer in both genders, and penile cancer in males. Moreover, genital warts are benign tumors which are HPV-related and can occur in both genders. This is a review of HPV structure, HPV infection transmission, the global impact of HPV and its associated diseases, HPV vaccines and their efficacy and safety, public acceptance of HPV vaccines, the obstacles for its acceptance and strategies to address the barriers. Cervarix(a bivalent vaccine with protection against HPV types 16 and 18) and Gardasil(a quadrivalent vaccine with protection against HPV types 6, 11, 16 and 18) are 2 recommended vaccines. The longest follow up of 9.4 years has shown efficacy and protection of the vaccine against HPV types 16 and 18. The adverse effects have been minimal and the vaccine is considered safe. Numerous studies are conducted to follow the vaccinated individuals to better understand the effect of HPV vaccine on incidence of HPV-related cancers and precancerous lesions.

Female genital schistosomiasis,human papilloma virus infection,and cervical cancer in rural Madagascar:a cross sectional study

Background Women’s health in resource-limited settings can benefit from the integrated management of high-burden diseases,such as female genital schistosomiasis(FGS)and human papilloma virus(HPV)-related cervical cancer.In schistosomiasis-endemic countries such as Madagascar,data on FGS and HPV prevalence are lacking as well as preventive measures for both conditions.This study aims to estimate the prevalence of FGS and HPV in rural Madagascar,and to examine associated risk factors to identify opportunities for improving women’s health.Methods After initial community outreach activities,interested women aged 18-49 years were recruited consecutively in 2021 at three primary health care centers in the district of Marovoay.FGS was detected by colposcopy.Colposcopy images were double-blind reviewed by two independent specialists.A Luminex bead-based assay was performed on cervical vaginal lavage specimens for HPV typing.Crude(CPR)and adjusted prevalence ratios(APR)of associations between selected factors and FGS and HPV positivity were estimated using univariable and multivariable binary Poisson regression with 95%confidence intervals(CIs).Results Among 500 women enrolled,302 had complete information on FGS and HPV diagnosis,and were thus eligible for analysis.Within the sample,189(62.6%,95%CI:56.9-68.1)cases of FGS were detected.A total of 129 women(42.7%,95%CI:37.1-48.5)tested positive for HPV.In total,80 women(26.5%,95%CI:21.6-31.8)tested positive for both conditions.No association was observed between FGS and HPV positivity,while previous pregnancy(APR=0.65,95%CI:0.43-0.78)and older age(APR=0.59,95%CI:0.42-0.81)are showing a negative association with HPV infection compared to no previous pregnancy and younger age groups.Conclusions The results of the study show that FGS and HPV are highly prevalent in rural Madagascar.The concurrent prevalence of these two conditions requires urgent adaptations of public health strategies to improve women’s health,such as integrated services at primary level of care.

Detection of Human Papillomavirus DNA in Oral Cancer Tissue Using Polymerase Chain Reaction

Using polymerase chain reaction (PCR), 25 specimens from 22 patients with oral carcinomas were examined by 6 selected primers of human papillomavirus (HPV). Eighteen of the 22 patients (18/22) gave positive reaction with a positive rate of 81.8%. The positive rates of HPV 6, 11, 16 and 18 were 27.3%, 18.2%, 63.6% and 40.9% respectively. 13.6% positive for mixed infection of HPV 16 and 18 (3/22) and 18.2% positive for mixed infection of HPV, 6, 11, 16 and 18 (4/22). Examining enlarged cervical lymph nodes in three cases with suspecting metastases to cervical lymph nodes from oral carcinomas. It revealed HPV DNA 16 and 18 in two cases and HPV DNA 18 in one case. These results suggested that there was a tendency for HPV 16 and 18 to metastasinze via lymphatics. Only one case of the three had a pathologic diagnosis of lymph node metastasis. Of the 30 non tumor controls, HPV DNA positivity was 10%, all being HPV 18. χ 2 test gave a P<0.005. It strongly indicated that HPV 16 and 18 were related to oral carcinomas.

Clinical and scientific impact of human papillomavirus on head and neck cancer

Head and neck cancer(HNC) arises from the skull base to the clavicles and is the fifth most common cancer in the world by incidence. Historically, in the developed world HNC was associated with tobacco use and alcohol consumption, and the combination of the two produced a synergistic increase in risk. However, beginning in 1983, investigators have found a significant and growing proportion of HNC patients with human papillomavirus-positive(HPV) tumors who neither drank nor used tobacco. Since that time, there has been increased interest in the molecular biology of HPV-positive HNC. Multiple studies now show that HPV has shifted the epidemiological landscape and prognosis of head and neck squamous cell carcinoma(HNSCC). These studies provide strong evidence for improved survival outcomes in patients with HPV-positive HNSCC compared to those with HPV-negative HNSCC. In many reports, HPV status is the strongest predictor of locoregional control, disease specific survival and overall survival. In response to these findings, there has been significant interest in the best management of HPV-positive disease. Discussions within major cooperative groups consider new trials designed to maintain the current strong survival outcomes while reducing the long-term treatment-re-lated toxicities. This review will highlight the epidemiological, clinical and molecular discoveries surrounding HPV-related HNSCC over the recent decades and we conclude by suggesting how these findings may guide future treatment approaches.

Sequence analysis of human papillomavirus type 16 E6E7 gene from cervical carcinoma biopsies of Chinese patients in Shandong province

Objective To study the structure specificity of HPV16E6E7 gene from cervical carcinoma biopsies of patients in Shandong province. Methods The tissue DNAs were extracted from cervical carcinoma biopsies of 14 patients of Chinese from Shandong province. By PCR method using HPV multiple primers, the HPV types were identified in cervical carcinoma tissues, Using the tissue DNA of the 2 cases with the infection of HPV16 type only as templates, HPV16E6E7 gene was amplified by PCR respectively, then inserted the HPV16E6E7 gene into pALTER I vector, and obtained the recombinant plasmid pALTER HPV16E6E7. The constructs were sequenced using Sanger method, and then compared with the sequence of HPV16E6E7 gene of the prototype. Results Sequencing results showed that HPV16E6E7 gene in the 2 cases had sequence diversity from that of the prototype, and a total of five nucleotide exchanges were detected, four of these led to amino acid exchanges. Conclusion There are structure differences between the HPV16E6E7 of Chinese and that of the prototype.

不同治疗方案对宫颈高危型HPV感染患者的治疗效果分析

目的:探讨多种治疗方案对宫颈高危型人乳头瘤病毒(HPV)感染患者的临床治疗效果,为HPV患者的临床治疗提供新思路。方法:采用回顾性研究方法纳入2022年1月—2023年1月在宜昌市中心人民医院治疗的宫颈高危型HPV感染患者501例,根据患者选取的治疗方法分为三组,A组患者给予保妇康栓治疗(n=167),B组患者给予重组人干扰素α-2b凝胶治疗(n=167),C组给予抗HPV生物蛋白敷料治疗(n=167)。比较三组HPV患者治疗有效率、HPV-DNA水平、治疗后HPV阳性率和治疗过程中不良反应发生率,评价临床治疗效果。结果:C组患者治疗总有效率明显高于A组(90.42%vs 74.85%)和B组(90.42%vs 77.25%)(均P<0.05)。三组患者治疗3个月及6个月HPV-DNA水平较治疗前明显下降,且治疗3个月及6个月时,C组患者的HPV-DNA水平较A组和B组明显降低(均P<0.05)。治疗后C组HPV阳性率明显低于A组(6.60%vs 22.75%)和B组(6.60%vs 20.96%)(均P<0.05)。三组患者不良反应发生情况无明显统计学差异(P>0.05)。结论:抗HPV生物蛋白敷料对于宫颈高危型HPV感染患者的治疗效果优于保妇康栓及重组人干扰素α-2b凝胶,且不良反应发生少,值得临床上进一步推广。

复方沙棘籽油栓治疗慢性宫颈炎合并高危型HPV感染有效性和安全性Meta分析

目的基于Meta分析系统评价复方沙棘籽油栓联合rhIFNα-2b栓治疗慢性宫颈炎(CC)合并高危型人乳头瘤病毒(HPV)感染的有效性与安全性。方法检索中国知识资源总库(CNKI)、中国生物医学文献服务系统(SinoMed)、中国学术期刊数据库(万方数据)、中文科技期刊数据库(VIP)、中国临床试验注册中心、PubMed、Cochrane Library建库至2022年7月1日收录的复方沙棘籽油栓治疗CC合并高危型HPV感染的随机对照试验(RCT)文献,进行数据提取和文献质量评价,运用RevMan5.4软件进行Meta分析和亚组分析。结果共纳入RCT文献10篇,试验组和对照组患者共1432例。与单独使用重组人干扰素(rhIFN)α-2b栓相比,联用复方沙棘籽油栓可显著提高CC合并高危型HPV感染的临床总有效率(RR=1.20,95%CI[1.15,1.26],P=0.79,I^(2)=0%)和治愈率(RR=1.40,95%CI[1.18,1.66],P=0.67,I2=0%),差异均有统计学意义;复方沙棘籽油栓联合rhIFNα-2b栓治疗可提高HPV转阴率,疗程越长效应越大,54天组(RR=1.14,95%CI[1.06,1.22],P=0.32,I^(2)=14%)、60天组(RR=1.61,95%CI[1.26,2.06],P=0.75,I^(2)=0%),84天组(RR=1.83,95%CI[1.26,2.64],P=0.05,I2=66%)。结论复方沙棘籽油栓联合rhIFNα-2b栓治疗CC合并高危型HPV感染的临床总有效率、治愈率和HPV转阴率均优于单用rhIFNα-2b栓,且无不良反应事件发生。

HPV与宿主基因整合在宫颈病变发生发展中的作用机制研究进展

宫颈癌病死率较高,高危人乳头瘤病毒(HPV)持续感染是其主要致病原因,其中HPV与宿主基因整合在宫颈病变的发生发展中发挥关键作用。目前,以三代测序技术为代表的新兴技术已用于HPV整合位点及基因改变等的相关检测。HPV整合后可能通过基因扩增、染色体结构改变、改变DNA序列甲基化状态、形成染色体外DNA、导致宿主致癌基因激活和抑癌基因失活以及影响微RNA的表达等发挥促癌作用。因此,深入研究HPV与宿主基因整合在宫颈病变发生发展中的作用机制,可以为相关疾病的治疗提供新思路。