Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis,prognosis and recurrence risk in patients with cervical epithelioma

BACKGROUND Cervical intraepithelial neoplasia(CIN)is an important precursor of cervical cancer.Early detection and treatment can reduce the incidence of cervical cancer.AIM To investigate the detection rate of human papillomavirus(HPV)E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia(CIN)and its relationship with CIN progression and diagnosis.METHODS One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected.These patients were graded CIN based on colposcopy and cervical pathology.The positive expression rates of HPV E6/E7 mRNA and HPV[polymerase chain reaction(PCR)-reverse dot crossing]were compared among all groups.Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr.The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis.RESULTS The diagnostic sensitivity,specificity,and sensitivity of PCR-reverse point hybrid ization technology for secondary CIN were 70.41%,70.66%,and 0.714,respectively.Sensitivity and specificity for secondary CIN were 752%and 7853%,respectively,the area under the curve value was 0.789.Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I(P<0.05).In CIN grade I patients with positive for HPV E6/E7 mRNA,in its orientation to grade CIN patients,in its orientation to grade CIN patients,at 69.2%,compared with patients negative for HPV E6/E7 mRNA(30.8%),significant difference(P<0.05).CONCLUSION HPV E6/E7 mRNA and HPV(PCR-reverse dot hybrid)positive expression have a close relationship with CINgrade disease progression and is an independent risk factor for high-grade CIN lesions.

Distribution of high-risk human papillomavirus genotype prevalence and attribution to cervical precancerous lesions in rural North China

Objective: Precise prevention is more desired for cervical cancer due to the huge population, high prevalence of human papillomavirus(HPV) infection in China and the vision of screen-and-treat strategies in low-and middleincome countries(LMICs). Considerations of combining type-specific prevalence and attribution proportion to high-grade cervical intraepithelial neoplasia are informative to more precise and effective region-specific cervical cancer prevention and control programs. The aim of the current study was to determine the genotype distribution of HPV and attribution to cervical precancerous lesions among women from rural areas in North China.Methods: A total of 9,526 women participated in the cervical cancer screening project in rural China. The samples of women who tested positive for HPV were retested with a polymerase chain reaction(PCR)-based HPV genotyping test. The attribution proportion of specific high-risk human papillomavirus(HR-HPV) types for different grades of cervical lesions was calculated by using the type contribution weighting method.Results: A total of 22.2%(2,112/9,526) of women were HR-HPV positive and HPV52(21.7%) was the most common HR-HPV genotype, followed by HPV58(18.2%), HPV53(18.2%) and HPV16(16.2%). The top three genotypes detected in HR-HPV-positive cervical intraepithelial neoplasia(CIN)1 were HPV16(36.7%), HPV58(20.4%), HPV56(15.3%). Among CIN2+, the most frequent genotypes were HPV16(75.6%), HPV52(17.8%),HPV58(16.7%). HPV16, 56, 58, 53, 52, 59, 68, and 18 combined were attributed to 84.17% of all CIN1 lesions,and HPV16, 58, and 52 combined were attributed to 86.98% of all CIN2+ lesions.Conclusions: The prevalence of HR-HPV infection among women from rural areas in North China was high and HPV16, HPV58, HPV52 had paramount attributable fraction in CIN2+. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.

Expression and Significance of SHP-2 in Human Papillomavirus Infected Cervical Cancer

This study investigated the expression and prognostic value of SHP-2 in cervical cancer caused by human papillomavirus (HPV) infection. Forty-five specimens from patients with cervical cancer (stageⅠ-Ⅲ), 32 specimens from patients with cervical intraepithelial neoplasia (CIN) (Ⅰ, Ⅱ) and 20 normal cervical samples from patients with hysteromyoma were collected in Department of Pathology for comparison. The expression levels of SHP-2 and IFN-β proteins were detected by using immunohistochemistry. The mRNA expression level of SHP-2 was detected by using quantitative real-time polymerase chain reaction (PCR). HPVs were detected by HPV GenoArray Test. The Spearman correlation was used to compare the expression level of SHP-2 in HPV infected cervical cancer vs non-HPV infected normal cervix. The level of SHP-2 protein expression in the cancer tissues (88.8%) was significantly higher than in CIN tissues (62.5%) and normal cervixes (45%) (P<0.05 and P<0.05, respectively). The SHP-2 mRNA levels in the cancer tissues were upregulated as compared with those in the normal cervixes (P<0.05). Twenty-one (46.7%) cervical cancers, 25 (78.1%) CINs and 17 (85%) normal cervixes showed IFN-β positive staining in cytoplasm. There was statistically significant difference in the expression rate of IFN-β between cervical cancer and normal cervix (χ2=8.378, P<0.05) as well as between cervical cancer and CIN (χ2=7.695, P<0.05). HPV16/18 infections could be found in normal cervixs (15%), CINs (68.7%) and cervical cancers (84.4%). There was a correlation between HPV infection and SHP-2 expression in cervical cancer (rs=0.653, P<0.05). SHP-2 may be a useful prognostic and diagnostic indicator for HPV infected cervical cancer. In cervical cancers, SHP-2 mRNA and protein overexpression was associated with IFN-β lower-expression.

New cheaper human papilloma virus mass screening strategy reduces cervical cancer incidence in Changsha city:A clinical trial

BACKGROUND Cervical cancer is the second leading cause of death in women worldwide,second only to breast cancer.Around 80%of women have been infected with human papillomavirus(HPV)in their lifetime.Early screening and treatment are effective means of preventing cervical cancer,but due to economic reasons,many parts of the world do not have free screening programs to protect women’s health.AIM To increase HPV cervical cancer screening in Changsha and reduce the incidence of cervical cancer.METHODS Cervical cancer screening included gynecological examination,vaginal secretion examination and HPV high-risk typing testing.Cervical cytology examination(ThinPrep cytology test)was performed for individuals who test positive for HPV types other than 16 and 18.Vaginal colposcopy examination was performed for HPV16 and 18 positive individuals,as well as for those who were positive for ThinPrep cytology test.If the results of vaginal colposcopy examination were abnormal,histopathological examination was performed.We conducted a cost-benefit analysis after 4 years.RESULTS From 2019 to 2022,523437 women aged 35-64 years in Changsha city were screened and 73313 were positive,with a 14%positive rate.The detection rate of precancerous lesions of cervical cancer was 0.6%and the detection rate of cervical cancer was 0.037%.Among 311212 patients who underwent two cancers examinations,the incidence rate was reduced by more than half in the second examination.The average screening cost per woman was 120 RMB.The average cost of detecting early cases was 10619 RMB,with an early detection cost coefficient of 0.083.CONCLUSION Our screening strategy was effective and cost-effective,making it valuable for early diagnosis and treatment of cervical cancer.It is worth promoting in economically limited areas.

Suppression of human papillomavirus type 16 E5 oncoprotein:A promising step in fostering the treatment of cervical cancer

Cervical cancer is a growing global disease in developing countries.Persistent infection with human papillomaviruses(HPV)is an essential causative agent in this type of cancer.Several studies demonstrate HPV E5 oncoprotein can impress the normal life cycle of HPV-infected cells by targeting some pivotal cellular signaling pathways,such as the epidermal growth factor receptor(EGFR)signaling pathway.In this study,we used E5-siRNA to knockdown that essential oncogene and considered the effect of E5 silencing on proliferation,apoptosis,cell cycle,apoptosis-related gene expression,and the initiator of the EGFR signaling pathway in cervical cancer cells.The results demonstrate that E5 plays an essential role in the proliferation and inhibited apoptosis in cervical cancer.Furthermore,silencing E5 reduces proliferation,increases apoptosis,and elevates related-genes expression of these malignant cells.Overall,E5 suppression may be appropriate for ameliorating cervical cancer progression.

Evaluation of Awareness of Human Papillomavirus and Cervical Cancer among Female Undergraduates of a Private Mission University in Southwestern Nigeria

Background: Human papillomavirus infection is most prevalent in the younger population and causes cervical cancer, which is the leading cause of cancer death worldwide. In 2018, cervical cancer was estimated to be 570,000 cases and 311,000 deaths;it ranked as the fourth most commonly diagnosed cancer and the fourth leading cause of cancer death in women. Cervical cancer can be prevented through health education and vaccination against HPV. This study aimed at evaluating the level of awareness of human papillomavirus and cervical cancer among female undergraduate students of Babcock University, Ogun state of Nigeria. Methodology: This was a cross-sectional, questionnaire-based study conducted among 310 female undergraduates of Babcock University in Nigeria from January to April 2019. The selection technique was a multistage random sampling method. The data collection was done using structured and self-administered questionnaires. Data collected were analyzed using IBM Statistical Package for Social Sciences (SPSS) statistics for windows version 25 and were presented in summary charts and frequency tables. P-values less than or equal to 0.05 were considered statistically significant. Results: Of 310 female students, 296 (95.5%) were aware of HPV infections. The majority, 215 (69.4%) of the students knew that HPV is sexually transmitted. There was poor knowledge of the risk factors of HPV infection. Only, 65 (21.0%) were aware that HPV infection causes cervical cancer. A few proportions of students 79 (25.4%) were aware of the HPV vaccine. Consequently, only 44 (14.2%) have received HPV vaccination and some complained about the cost as a significant reason for not being vaccinated against HPV infection. Conclusion: The level of awareness of HPV infection, cervical cancer, and HPV vaccine uptake was very low in this study. There is a need to improve health education and awareness campaigns among students about HPV infection, cervical cancer, and HPV vaccine uptake.

Human Papillomavirus—The Cause of Human Cervical Cancer

Objective: Cervical cancer is the second most prevalent cancer in females worldwide. Infection with human papillomavirus (HPV) is regarded as the main risk factor of cervical cancer. One objective of this study was to conduct a qualitative systematic review of some case-control studies and to examine the role of human papillomavirus (HPV) in the development of human cervical cancer (CC) beyond any reasonable doubt. Methods: We conducted a systematic review and re-analysis of some impressive key studies aimed to answer the following question. Is there a cause-effect relationship between human papillomavirus and cervical cancer? The method of the conditio sine qua non relationship was used to proof the hypothesis whether the presence of human papillomavirus guarantees the presence of cervical carcinoma. In other words, if human cervical cancer is present, then human papillomavirus is present too. The mathematical formula of the causal relationship k was used to proof the hypothesis, whether there is a cause-effect relationship between human papillomavirus and cervical carcinoma. Significance was indicated by a p-value of less than 0.05. Result: The studies analyzed (sample size N = 7657) were able to provide strict evidence that human papillomavirus is a necessary condition (a conditio sine qua non) of cervical carcinoma. Furthermore, the studies analyzed provide impressive evidence of a cause-effect relationship (k = +0.723669245, p value < 0.00001) between human papillomavirus and cervical carcinoma. Conclusion: Human papillomavirus is the cause of human cervical carcinoma.

Expression and clinical significance of high risk human papillomavirus and invasive gene in cervical carcinoma

Objective:To study the expression of E6 and E7 mRNA in high-risk human papillomavirus(HPV) HPV-18 and the relationship between the expression of invasive gene and cervical carcinoma.Methods:A total of 119 patients with cervical cancer,cervical erosion and cervical HPV infection who were diagnosed in our hospital were selected and randomly divided into two groups:cervical cancer group(n= 58) and non-cancerous group(n= 61).Another 60 patients with uterine leiomyoma were selected as normal control group.Detection of HPV18 E6,E7 mRNA expression and invasion,migration,proliferation inhibition genes,epithelial mesenchymal transition genes and proliferation related protein content.Results:The relative expression of E6 and E7 HPV-18 in cervical cancer group was significant higher than that in non-cancerous group and control group(mRNA)(P<0.05).The content of TRAF6 and c-FLIP in invasive cervical cancer group was significantly higher than that in non-cancerous group and control group(P<0.05).The mR NA content of CD44v6 and MMP-9 in cervical cancer group was significantly higher than that in non-cancerous group and control group(P<0.05).The content of DEC-1,IKK16,MBP-1 in cervical cancer group was significant lower than that in non-cancerous group and control group(P<0.05).The mR NA content of beta-catenin and Vimentin in cervical cancer group was significantly lower than that in non cancerous group and control group(P<0.05).The proliferation related protein E2F1 of cervical cancer group was significantly lower than that of non-cancerous group and control group,Bmi-1 content was significantly higher than non-cancerous group and control group(P<0.05).Conclusions:The expression of the detection of cervical cancer in high-risk human papilloma virus HPV-18 E6 and E7 mRNA,and the invasion,migration,proliferation inhibition gene,epithelial mesenchymal transition and proliferation related gene protein content,HPV expression rate of mR NA increased with the development of cervical cancer,the expression is also enhanced.The expression has a certain correlation between the level and development of cervical cancer.Through the above indicators,the development of cervical cancer monitoring and treatment to provide important clinical guidance.

The Prevalence of High Grade Cervical Intraepithelial Neoplasia (CIN) in a Primary Human Papillomavirus (HPV) Cervical Screening Programme Population with HPV Positive and Cytology Negative Smear Results

High-risk HPV is found in 99.7% of cervical cancers. The causative role of HPV in cervical cancer has led to the inclusion of HPV testing as part of cervical screening. A pilot of HPV testing as primary screening was commenced in 2013 at six pilot sites in England. North Cumbria Integrated Care (NCIC) NHS Foundation Trust took part in the pilot, in which women with an HPV-positive/cytology-negative result were recalled at 12 months. Women with HPV type 16/18 found at initial screening and persisting at 12 months in spite of negative cytology were referred to Colposcopy services at 12 months. Women with smear positive for hrHPV other than 16/18 types were recalled twice at 12 and 24 months before referral to colposcopy. Persistent hrHPV positive/cytology negative smear at 12 and 24 months initiated a colposcopy referral. Objective: To assess the prevalence of high grade CIN and invasive cancer in patients referred to colposcopy services at NCIC NHS Foundation Trust with hrHPV positive/cytology negative smears. Method: The study was conducted at NCIC NHS Foundation Trust between January 2015 and December 2017. Data was collected retrospectively from the colposcopy data base (INFOFLEX). All patients with HPV positive/cytology negative smears seen in colposcopy clinic during the study period were included. Patients with high grade CIN, cervical glandular intraepithelial neoplasia (CGIN) or invasive cancer were recorded. Results: 763 women were included in the study. A total of 50 (6.6%) women had high grade CIN, CGIN or invasive cancer. 40 of these 50 women (80%) were treated by large loop excision of the transformation zone (LLETZ). Conclusion: HPV primary screening is more effective than cytology-based screening. A high grade HPV positive result with negative cytology, persisting for one year in type 16/18 and for two years in other high-risk HPV types, warrants referral for colposcopy, as 6.6% of women in this study had high grade or invasive pathology.

SEARCH FOR HERPES SIMPLEX VIRUS TYPE2（HSV－2）AND HUMAN PAPILLOMAVIRUS（HPV）IN THE NORMAL AND ABNORMAL CERVICAL SAMPLES

The specimens of 111 cervical carcinomas. 68 chronic cervicitis and 43 normal cervical exfoliated epithelial cells were examined for the presence of HSV2 DNA sequences with DNA hybridization using HSV2 BgL Ⅱ N fragment probe labelled by 32PdCTP. The result showed that the infection rates of HSV2 in the samples of cervical cancer.chronic cervicitis and normal epithelial cells were 1 4. 41 %(16/111). 27.94%( 19/68) and 25.58% ( 11/43),respectively. It was implied that early stages carcinogenesis of cervical epithelial cells might be correlated with the HSV2 infection.Sixteen HSV 2 positive samples of cervical carcinomas were also examined for the presence of the sequences homologous to human papillomavirus (HPV) type 6B/11. 16 and 18 DNA using dot blot hybridization (Tm17℃). The result indicated that 13 out of 16 were HPV 16 DNA hybridization positive accounting for 81. 2% of all HSV-2 positive samples and none of them were positive for HPV type 6B/11 and 18. The result indicated that double infection of HSV 2 and HPV16 in the same cervical carcinoma tissues may provide a strong evidence of the viral synergistic interaction in the induction of female cervical

Distribution of High-Risk Human Papillomavirus Genotypes among Women with Colposcopic Diagnosis of Cervical Intraepithelial Neoplasia in Bangladesh

Background: The incidence of cervical cancer is high in Bangladesh and there is a high prevalence of preinvasive lower genital tract disease among women of reproductive age. Persistent high-risk Human Papilloma Virus (HPV) infection is the main underlying cause of cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN). Objective: The aim of the study was to identify the subtypes of high-risk HPV infection among women with the colposcopic diagnosis of cervical intraepithelial neoplasia in Bangladesh. Methods: This cross-sectional observational study was conducted in the colposcopy clinic of Dhaka Medical College Hospital over a six-month period. A total of 100 participants were enrolled. Married women, between 30 - 60 years of age with colposcopically diagnosed cervical intra epithelial neoplasia were enrolled. Women with chronic illness, pregnancy, and women unable to consent were excluded from this study. After counselling, colposcopically directed punch biopsies were taken from each CIN case concurrently with high-risk HPV testing by polymerase chain reaction (PCR). Results: The mean age of the patients was 38.69 (SD ±7.76) years. CIN 1 was diagnosed in 57% of participants, while 24% had CIN II and 19% had CIN III lesions. High-risk HPV was present in 52 patients. HPV 16 was the most common identified in 28 (53.84%) and HPV 18 was the second most common with 20 (38.46%) either singly or in combination with other high-risk subtypes. The other HPV strains, HPV 31, 33, 35, 52, 56 and 58, were also detected either as mono or co-infections. Out of the 52 HPV positive cases, 29 (55.8%) had mono infection and 23 (44.2%) had co-infection with several subtypes. The highest incidence (50%) of oncogenic HPV infections was present among women aged 35 - 45 years. Risk factors associated with HPV positive cases were high parity (P 0.05), early age at marriage (P = 0.754) and early age of first child. Conclusion: This study identified a high prevalence of HPV 16 and 18 genotypes. HPV vaccination with the current 9-valent HPV vaccine, which contains HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Will be an effective public health measure to eradicate cervical cancer in Bangladesh.

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.

Accuracy of triage strategies for human papillomavirus DNA-positive women in low-resource settings:A cross-sectional study in China

Objective： CareHPV is a human papillomavirus （HPV） DNA test for low-resource settings （LRS）. This study assesses optimum triage strategies for careHPV-positive women in LRS. Methods： A total of 2,530 Chinese women were concurrently screened for cervical cancer with visual inspection with acetic acid （VIA）, liquid-based cytology and HPV testing by physician- and self-collected careHPV, and physician-collected Hybrid Capture 2 （HC2）. Screen-positive women were referred to colposcopy with biopsy and endocervical curettage as necessary. HPV-positivity was defined as _〉1.0 relative light units/cutoff （RLU/CO） for both careHPV and HC2. Primary physician-HC2, physician-careHPV and self-careHPV and in sequential screening with cytology, VIA, or increased HPV test-positivity performance, stratified by age, were assessed for cervical intraepithelial neoplasia （CIN） grade 2/3 or worse （CIN2/3＋） detection. Results： The sensitivities and specificities of primary HPV testing for CIN2＋ were： 83.8%, 88.1% for physician- careHPV; 72. 1%, 88.2% for self-careHPV; and 97.1%, 86.0% for HC2. Physician-careHPV test-positive women with VIA triage had a sensitivity of 30.9% for CIN2＋ versus 80.9% with cytology triage. Self-careHPV test- positive women with VIA triage was 26.5% versus 66.2 % with cytology triage. The sensitivity of HC2 test-positive women with VIA triage was 38.2 % versus 92.6% with cytology triage. The sensitivity of physician-careHPV testing for CIN2＋ decreased from 83.8% at _〉1.0 RLU/CO to 72.1% at _〉10.00 RLU/CO, while the sensitivity of self- careHPV testing decreased from 72.1% at _〉1.0 RLU/CO to 32.4% at _〉10.00 RLU/CO; similar trends were seen with age-stratification. Conclusions： VIA and cytology triage improved specificity for CIN2/3 than no triage. Sensitivity with VIA triage was unsuitable for a mass-screening program. VIA provider training might improve this strategy. Cytology triage could be feasible where a high-quality cytology program exists. Triage of HPV test-positive women by increased test positivity cutoff adds another LRS triage option.

Co-infection of Epstein-Barr virus and human papillomavirus in human tumorigenesis

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.

Comparison of Human Papillomavirus Detection and Genotyping with Four Different Prime Sets by PCR-Sequencing

Objective To assess and compare the Human Papillomavirus（HPV） detection efficiency and the potential clinical utility of PCR sequencing‐based technology.Methods Four HPV consensus primer sets（GP5＋/6＋,MGP,MY09/11,and PGMY09/11） were used in order to amplify a broad spectrum of HPV types for HPV infection in 325 cervical samples and the PCR products were sequenced afterwards for the HPV genotyping.Results The HPV‐positive rate was 75.4%,of which 35.5% harbored more than one HPV genotype.A total of 36 different genotypes was found,with HPV 16（24.1%） being the most prevalent,followed by HPV 58（13.3%） and HPV 52（9.6%）.There were substantial to almost perfect agreements between different primer sets regarding HPV detection efficiency,with the kappa value varying from 0.751 to 0.925,MGP,and PGMY09/11 were the most effective in detecting multiple infections（P0.001）.With each of the primer sets,a board range of HPV types could be identified,though there were several differences for a few genotypes.Conclusion The substantial agreement between PCR‐sequencing and HC2 for the detection of high‐risk HPV（kappa=0.761） indicated that PCR‐sequencing is also suitable for routine HPV screening.

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.

Association between Helicobacterpylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas

AIM TO correlate Helicobacter pylori （H. pylorli）, EpsteinBarr virus （EBV） and human papillomavirus （HPV） with gastric cancer （GC） cases in Para State, Brazil.METHODS Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eberl RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.RESULTS The majority of the 302 samples analyzed were obtained from men （65%） aged 55 years or older （67%） and were classified as the intestinal subtype （55%）. All three pathogens were found in the samples analyzed in the present study （H. pylori： 87%, EBV： 20%, HPV： 3%）. Overall, 78% of the H. pylori-positive （H. pylorl＋） samples were cagA＋ （H. pylori-cagA＋）, and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA＋ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.CONCLUSION HPV was not involved in gastric tumorigenesis. Prophy- lactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms.

High-risk Human Papillomavirus Infection and Associated Factors among HIV-positive Women in High HIV-burden Areas of China

Persistent high-risk human papillomavirus(hrHPV)infection is a necessary factor for precancerous cervical intraepithelial neoplasia and invasive cervical cancer.HPV infection and persistent infection are associated with poor body immunity.Human immunodeficiency virus(HIV)-positive women are susceptible to HPV infection due to the immunosuppression caused by HIV infection[1].Hence,women infected with HIV face a heightened risk of developing precancerous lesions and cervical cancers.

Safety and immunogenicity of human papillomavirus-16/18 AS04-adjuvanted vaccine in healthy Chinese females aged 15 to 45 years:a phase Ⅰ trial

Globally,about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection.A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples.The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions.This phase Ⅰ trial (NCT00549900) assessed the safety,tolerability,and immunogenicity of the vaccine in Chinese.Thirty healthy Chinese females,aged 15 to 45 years with a median age of 29.5 years,received three doses of Cervarix in Months 0,1,and 6.Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination.Serious adverse events,new onset of chronic diseases,and other medically significant conditions were recorded throughout this trial.As an exploratory objective,HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7.Pain at the injection site was the most frequently reported local symptom.Two subjects reported medically significant adverse events.Both cases were assessed as unrelated to vaccination by the investigator.In Month 7,100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers.HPV-16/18 AS04-adjuvanted vaccine,evaluated for the first time in Chinese females,was generally well tolerated and immunogenic,as previously shown in global studies.

Update on human papillomavirus vaccination: Where are we now?

Infection with human papillomavirus(HPV) is the major cause of pre-invasive and invasive lesions of the urogenital tract, resulting in morbidity and mortality worldwide. HPV-related infection is responsible for most cases of cervical cancer, a leading cause of cancer death in women worldwide. Developed countries have screening programs in place to detect precancerous lesions at early stages; in resource-limited settings however, HPV related diseases are often identified in advanced stages. This is due to limitations in the availability and roll out of effective screening programs. The relatively recent availability of the HPV vaccine has provided a new public health opportunity to decrease the incidence of HPV-related disease. The high mortality rates seen in developing countries could be reduced through effective implementation of HPV vaccination programs. Large trials have proven the efficacy of bivalent, quadrivalent vaccine and most recently 9-valent vaccine. Uptake in vaccination remains low due to multiple barriers including lack of education, lack of access, and costs. New strategies are being assessed to increase access, increase knowledge and reduce costs that may result in feasible vaccination programs worldwide. The goal of this article is to review the effectiveness and safety of the current HPV vaccines available, vaccine delivery strategies, cost effectiveness, and efforts to improve the acceptability. A literature search was conducted through Pub Med using the terms "HPV vaccination, and safety, and males, and acceptability and strategies, and cost effectiveness,"focusing on articles published between 2006 and 2015. The most relevant and larger scale trials were evaluated for discussion.