Traditional Chinese Medicine Erhuang Suppository for Treatment of Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix

Objective High-risk human papillomavirus(HR-HPV)infection is the chief cause of cervical intraepithelial neoplasia(CIN)and cervical carcinoma.The Erhuang suppository(EHS)is a traditional Chinese medicine(TCM)prepared from realgar(As2S2),Coptidis rhizoma,alumen,and borneolum syntheticum and has been used for antiviral and antitumor purposes.However,whether EHS can efficiently alleviate HR-HPV infection remains unclear.This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix.Methods In this study,we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up.Totally,70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo.HPV DNA,ThinPrep cytologic test(TCT),colposcopy,and safety evaluation were carried out after treatment.Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment.A K14-HPV16 mouse model was generated to confirm the efficiency of EHS.Results After 3 months,74.3%(26/35)of the patients in the treatment group were HPV negative,compared to 6.9%(2/29)in the placebo group.High-throughput microarrays revealed distinct transcriptome profiles after treatment.The differentially expressed genes were significantly enriched in complement activation,immune response,and apoptotic processes.The K14-HPV16 mouse model also validated the remarkable efficacy of EHS.Conclusion This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions.Additionally,no obvious systemic toxicity was observed in patients during the trial.The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.

Prevalence of Precancerous Lesions Based on Digital Cervicography with VIA/VILI among Women Positive for High-Risk Human Papillomavirus Serotypes: A Screening Center-Based Study in Cameroon

Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triage test, with or without biopsy, before treatment. Cameroon has rolled out immunization against HPV 16 and 18, but studies show a higher prevalence of non-16/18 HR-HPV types. Objectives: Determine the prevalence of precancerous lesions, in women with HR-HPV infection and evaluate association of digital cervicography (DC) VIA/VILI positivity with HPV serotype, as a measure of their contribution to precancer and cancer incidence. Methodology: The study was cross-sectional, descriptive, and analytic. It took place at the Etoug-Ebe and Ekoudoum Baptist Hospitals in Yaoundé, during the period April-September 2022. We reviewed the records of women screened for cervical cancer between February 2020 and December 2021 and evaluated the prevalence of lesions on digital cervicography (DC) with VIA/VILI for women positive for HR-HPV serotypes. The data were analyzed using SPSS version 20.0 for Windows. P values Results: We identified 315 cases with a positive HR-HPV deoxyribonucleic acid (DNA) test, 224 (71.1%) had a DC VIA/VILI triage test done. Of these, 30 (13.4%) women had a positive DC VIA/VILI, with five women (2.2%) having lesions suggestive of cancer. Out of 11 cases positive for HPV 16 alone, 05 (45.5%) had a positive DC VIA/VILI test. Of the 14 cases positive for HPV 18 alone, 03 (21.4%) had a positive VIA/VILI, meanwhile only 19 (10.7%) of the 177 cases positive for non-16/18 HPV had a positive VIA/VILI test. Conclusion: A high proportion of women (13.4%) with HR HPV had a positive DC VIA/VILI, with a significant proportion (2.2%) having lesions suggestive of invasive cervical cancer HR-HPV serotype was associated with DC VIA/VILI positivity;HPV 16 had the strongest association (45.5%), followed by HPV 18 (21.4%), and non-16/18 HR-HPV (10.7%), suggesting a decreasing order of oncogenicity.

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.

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.

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.

Importance of investigating high-risk human papillomavirus in lymph node metastasis of esophageal adenocarcinoma

High-risk human papillomavirus has been suggested as a risk factor for esophageal adenocarcinoma.Tumor human papillomavirus status has been reported to confer a favorable prognosis in esophageal adenocarcinoma.The size of the primary tumor and degree of lymphatic spread determines the prognosis of esophageal carcinomas.Lymph node status has been found to be a predictor of recurrent disease as well as 5-year survival in esophageal malignancies.In human papillomavirus driven cancers,e.g.cervical,anogenital,head and neck cancers,associated lymph nodes with a high viral load suggest metastatic lymph node involvement.Thus,human papillomavirus could potentially be useful as a marker of micro-metastases.To date,there have been no reported studies regarding human papillomavirus involvement in lymph nodes of metastatic esophageal adenocarcinoma.This review highlights the importance of investigating human papillomavirus in lymph node metastasis of esophageal adenocarcinoma based on data derived from other human papillomavirus driven cancers.

Clinical significance of extended high-risk human papillomavirus genotyping and viral load in cervical cancer and precancerous lesions

Persistent infections with specific high-risk human papillomavirus(HR-HPV)strains are the leading cause of cervical cancer and precancerous lesions.HPV-16 and HPV-18 are associated with more than 70%of cervical cancer.However,with recent widespread vaccination efforts against cervical cancer,the infection rates of HPV-16 and HPV-18 have decreased across all age groups,while the infection rates of other HR-HPV strains have increased.The non-16/18 HR-HPV strains play an important role in cervical lesions.These strains can be identified with extended genotyping,and the 2019 American Society for Colposcopy and Cervical Pathology(ASCCP)guidelines recommended an HPV-based testing to assess the risk of cervical disease in patients.We reviewed and analyzed the clinical benefits of applying extended HR-HPV genotyping,which was published by the International Agency for Research on Cancer(HPV-16,18,31,33,35,39,45,51,52,56,58,59,66,and 68),to cervical cancer screening.This review concluded that cervical cancer screening needs to include extended HR-HPV genotyping.The examination of extended HR-HPV genotyping in cervical intraepithelial lesions and cervical cancers can help guide clinical practices.

Mother-to-Child Transmission of Human Papillomavirus in Burkina Faso

Introduction: Human papillomavirus (HPV) infection is the most widespread sexually transmitted infection in the world. Today, there is growing evidence that HPV can be transmitted early in life, and one potential route is mother-to-child transmission. Data on this route of HPV transmission are scarce in Africa and particularly in Burkina Faso, where no data on the subject are yet available. The aim of our study was to estimate the rate of mother-to-child transmission of HPV infection and to identify circulating genotypes. Methodology: Cervico-uterine samples were collected from 100 full-term pregnant women and, buccal samples were obtained from their newborns at Hopital Saint Camille de Ouagadougou (HOSCO) by the specialist physician. HPV DNA amplification and genotyping were performed by PCR followed by hybridization using the HPV Direct Flow Chips kit, detecting 36 genotypes including 18 high-risk and 18 low-risk. Results: The prevalence of HPV in newborns was 8% (8/100). Six (6) HPV-positive neonates had HPV-positive mothers, while 2 HPV-positive neonates had HPV-negative mothers. The vertical transmission rate was 26.09% (6/23). Mother-newborn genotypes were concordant. However, the genotype profile of the newborns was more restricted than that of the mothers. Conclusion: HPV DNA was found in 8% of newborns in our study. The genotype profile of the mother-newborn pair was concordant. Asymptomatic HPV infection in a pregnant woman could constitute a risk factor for vertical transmission.

Hysteroscopic cervical biopsy for women with persistent human papillomavirus infection after loop electrosurgical excision procedure: A case report

BACKGROUNDAlmost all cases of cervical cancer can be attributed to human papillomavirus(HPV) infection. The loop electrosurgical excision procedure (LEEP) is widelyused to treat HPV-mediated disease;thus, cervical cancer is highly preventable.However, LEEP does not necessarily clear HPV rapidly and may affect theaccuracy of the results of ThinPrep cytology test (TCT) and cervical biopsy due tothe formation of cervical scars.CASE SUMMARYA 40-year-old woman underwent LEEP for cervical intraepithelial neoplasia grade1 approximately 10 years ago. Subsequent standard cervical cancer screeningsuggested persistent HPV-52 infection, but TCT results were negative. Cervicalbiopsy under colposcopy was performed thrice over a 10-year period, yieldingnegative pathology results. She developed abnormal vaginal bleeding after sexualactivity, persisting for approximately 1 year, and underwent hysteroscopy in ourhospital. Histopathologic evaluation confirmed adenocarcinoma in situ of theuterine cervix.CONCLUSIONPatients with long-term persistent, high-risk HPV infection and negative pathologyresults of cervical biopsy after LEEP are at risk of cervical cancer. Hysteroscopicresection of cervical canal tissue is recommended as a supplement tocervical biopsy because it helps define the lesion site and may yield a pathologicdiagnosis.

A study on the cognitive status of human papillomavirus among adult males in Tianjin based on the health belief model

Background:To understand the health beliefs and knowledge of human papillomavirus among adult males in Tianjin.Methods:An online questionnaire survey was conducted from 18 January 2023 to 6 March 2023 using snowball sampling method.Analyze the health belief scores and human papillomavirus(HPV)and HPV vaccine knowledge scores of adult males in Tianjin,and analyze their influencing factors.Results:A total of 388 adult males in Tianjin were surveyed,with an average total score of 3.23±0.04 for their health beliefs.Among them,the average scores for perceived severity,perceived susceptibility,perceived impairment,perceived benefit,and self-efficacy were 3.41±1.05,2.37±1.20,2.96±1.00,3.51±0.90,and 3.36±1.08,respectively.Multiple linear regression analyses showed education was a factor influencing health beliefs.The average total score of knowledge is 64.09±15.62,with 277 people scoring above 60,and a pass rate of 71.4%.Through multiple linear regression analysis,education level,emotional status,whether disease testing has been done,and whether family and friends have been diagnosed with HPV positive are the main influencing factors.Conclusion:The awareness rate of HPV among adult males in Tianjin is still acceptable,but there are still misconceptions.The overall level of health beliefs is moderate,and the perceived susceptibility level is low.It is necessary to strengthen health education on HPV related knowledge for males and improve their cognitive level.

Study on the Correlation between Human Papillomavirus and Mycoplasma genitalium Combined with TCT Detection

Objective: This study aims to explore the correlation between human papillomavirus (HPV) and Mycoplasma genitalium (CT) combined with TCT detection in cervical cancer screening. Method: A cross-sectional study design was adopted, and a total of 609 women who came to seek medical treatment were recruited as the study subjects. Combination testing was evaluated on cervical cancer screening by testing the women for HPV, CT with TCT detection and analyzing the relationship of cervical lesions with HPV and CT infection. Results: The study results showed that 21.57% of the subjects were infected with both HPV and CT, and 48.42% of the cases had abnormal TCT results at the same time. Further data analysis showed that HPV infection was significantly associated with abnormal TCT outcomes (p < 0.05), suggesting a possible synergistic effect of the two infections in cervical lesions. The combined sensitivity and specificity of HPV, CT and TCT detection were 21.57% and 48.42%, respectively, which were significantly higher than that of single detection. Conclusion: In summary, the results of this study support the importance of combined HPV, CT, and TCT testing in cervical cancer screening, and propose the hypothesis that combined testing may improve screening effectiveness. However, further large sample studies are needed to confirm this conclusion and explore the prospects of combined testing in clinical practice.

Evaluating the Association between Human Papillomavirus and Vulvar Cancer:A Comprehensive Analysis Using Bradford Hill Criteria

Background:The role of human papillomavirus(HPV)in the development of vulvar cancer(VC)has been widely studied,but findings have been inconsistent.Despite numerous meta-analyses exploring the potential link between HPV and VC,the association remains controversial due to inherent limitations in meta-analytic methods.Objectives:To address this controversy,the study aims to investigate the potential link between HPV and VC using the Bradford Hill criteria,which offer a more comprehensive framework for establishing causation.Methodology:The study began by extracting all relevant studies on the association between HPV and VC from the PubMed database.The potential links were then assessed by examining the data using the major postulates of the Bradford Hill criteria.To ensure the reliability of the findings,the methodologies of the identified studies were critically evaluated to account for possible false-negative and false-positive results.Results:The assessment of previous studies against the Bradford Hill criteria revealed that the major postulates were not fulfilled.Conclusion:Based on the findings,it can concluded that there is no causal association between HPV and VC.

Evaluation of dry specimen transport and processing time using an isothermal amplification high-risk human papillomavirus assay

Background:Dry specimen transport has shown equivalence to traditional liquid transport using a novel high-risk Human papillomavirus assay.Considering that dry transport might cross obstacles during cervical cancer screening in low and middle resource settings,this study was designed evaluate different processing time of dry specimen transport using the same isothermal amplification hrHPV assay.Methods:There were 564 women between the ages of 30–55 recruited from colposcopy clinic.For each patient,two endocervical samples were collected and placed into empty collection tubes by physician.Samples were stored at room temperature until analyzed for hrHPV using the AmpFire assay at two time points:2 days and 2 weeks.511 of the 564 participants with positive hrHPV were provided colposcopy exam and quadrant biopsy.Results:A total of 1128 endocervical samples from 564 patients were detected by the Ampfire assay.Good agreement was found between two time periods(Kappa
Standard error=0.67±0.04).Sensitivity(2days/2weeks)for CIN2t was 95.28%(95%CI:92.14%–98.42%)vs 90.57%(CI(86.65%–94.49%)and specificity(2days/2weeks)was 22.47%(CI 19.33%–25.61%)vs 28.15%(CI 24.23%–32.07%)respectively.The difference for Ampfire HPV detection in sensitivity for CIN2t for the two time periods was not significant(P=0.227),while the difference in specificity for CIN2t was significant(P=0.001).The difference in Ct values 29.23(CI 28.15–30.31)and 29.27(CI 28.19–30.35)between two time points was not significant(P?0.164).Conclusion:Processing dry brush specimens can be delayed up to 2 weeks.Using the AmpFire assay platform which supports cervical cancer prevention programs in low-to-middle-income countries(LMICs).

Analysis of Human Papillomavirus Infection in Cervical Exfoliated Cells

To screen patients with early cervical lesions by analyzing the infection of high-risk Human papillomavirus (HR-HPV). Research Methods: The cervical exfoliated cell specimens and their clinical data were collected. The HPV infection types of the collected specimens were detected by fluorescence quantitative PCR, and the correlation between HPV infection and clinicopathological features was analyzed statistically. Results: 725 cases were HR-HPV positive from 2605 cases, including 15 high-risk types of HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68. Different histological types ranged from NILM to HSIL, and the positive rate of HPV showed an increasing trend with the aggravation of cervical lesions. Conclusion: The positive rate of 15 high-risk HPV types in the collected specimens was 27.8%. Patients with early cervical lesions could be screened for 15 high-risk HPV infection types.

Prevalence of high-risk human papillomavirus infection in different cervical lesion among organized health-examination women in Shanghai, China

Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe the prevalence of HPV infection in different types of cervical lesions and to explore the relation between HPV viral load and the severity of cervical lesions. Methods To describe the HPV infection prevalence and viral load in different age groups, we retrospectively investigated 6405 cases of women who were organized by their units to take health-examination. They were given Hybrid Capture II tests between January 2005 and December 2006. The correlation between HPV viral load and pathology was assessed. Results Overall HPV infection prevalence was 29.1% （1864/6405）, while in women 18-20 years old it was 54.4% （31/57）, the highest among all age groups. After declining rapidly, HPV prevalence stabilized at about 30.0% in women aged 30 and older. Of the 6405 women, 1483 women had a colposcopic biopsy and 33.2% （492/1483） were positive for HPV DNA. Twenty-one percent of women with a normal diagnosis （238/1095） had HPV infection, a statistically significantly lower prevalence than in women with cervical lesions, including those with cervical intraepithelial neoplasia （68.8% in CIN1,66.7% in CIN2, and 76.5% in CIN3） or with cervical cancer （94.1%）. The correlation coefficient between viral load and cervical lesion severity was 0.134, which was not statistically significant （P=0.075）. Viral load values in women with CINs and cervical cancer were calculated, and no significant differences were identified. Conclusions The prevalence of high-risk HPV infection among women attending hospitals for health-examination in Shanghai is similar to the worldwide rate. HPV viral load can distinguish cervical lesions from normal individuals but cannot adequately predict the severity of cervical lesions.

Two less common human microRNAs miR-875 and miR-3144 target a conserved site of E6 oncogene in most high-risk human papillomavirus subtypes

Human papillomaviruses （HPVs） including high.risk （HR） and low-risk （LR） subtypes have distinguishable variation on both genotypes and phenotypes. The co- infection of multiple HR-HPVs, headed by HPV16, is common in cervical cancer in female. Recently accu- mulating reports have focused on the interaction be- tween virus and host, particularly the role of human microRNAs （miRNAs） in anti-viral defense by targeting viral genome. Here, we found a well-conserved target site of miRNAs in the genomes of most HR-HPVs, not LR-HPVs, by scanning all potential target sites of human miRNAs on 24 HPVs of unambiguous subtypes of risk. The site is targeted by two less common human miR- NAs, miR-875 and miR-3144, and is located in E6 onco- gene open reading frame （ORF） and overlap with the first alternative splice exon of viral early transcripts. In validation tests, miR-875 and miR-3144 were identified to suppress the target reporter activity markedly and inhibit the expression of both synthetically exogenous E6 and endogenous E6 oncogene. High level of two miRNAs can inhibit cell growth and promote apoptosisin HPV16-positive cervical cancer cells. This study pro- vides a promising common target of miRNAs for most HR-HPVs and highlights the effects of two low ex- pressed human miRNAs on tumour suppression.

Incidence of persistent and high-risk human papillomavirus infection and associated factors among HIV-positive women in China, 2015-2016

Background:Persistent human papillomavirus(HPV)infection is the necessary factor for cervical cancer.Human immunodeficiency virus(HIV)-positive women are a high-risk population for cervical cancer,but little is known about persistent HPV infection among HIV-positive women in China.We aimed to investigate the persistence and incidence of infection with high-risk HPV(hrHPV)and associated factors among HIV-positive women in China.Method:Using a prospective observational study design,we collected data from 670 HIV-positive women in five counties of three provinces through interviews,medical record reviews,health examination,and laboratory tests at a baseline survey in 2015 and a follow-up survey in 2016.We tested HIVpositive women for hrHPV infection using the Cobas 4800 HPV test,and analyzed factors associated with persistence and new incidence of hrHPV infection using logistic regression.Results:After an average of 15 months at follow-up,the persistence and new incidence rates of hrHPV infection were 38.0%(46/121,95%CI:29.2%-46.8%)and 8.3%(35/420,95%CI:5.7%-11.1%),respectively.HIV-positive women in Yunnan and Guangxi were more likely to have persistent hrHPV infections than those in Xinjiang(aOR=3.18,95%CI:1.00-10.14,p=0.05;aOR=6.38,95%CI:2.29-17.77,p<0.001).Migrant women had a higher rate of new hrHPV incidence than local women(aOR=4.48,95%CI:1.65-12.15,p=0.003).HIV-positive women from Xinjiang were 6.5 times more likely to be newly infected with hrHPV than those from Yunnan(95%CI:2.40-17.60,p<0.001).HIV-positive women with HBV infection had a higher risk of being infected with hrHPV than those without HBV infection(aOR=3.48,95%CI:1.13-10.71,p=0.029).Conclusions:The persistence and new incidence rates of hrHPV infection among HIV-positive women were high and varied significantly between regions.HBV infection and being among the migrant population were associated with new hrHPV infection.

Efficacy of 2LPAPI®, a Micro-Immunotherapy Drug, in Patients with High-Risk Papillomavirus Genital Infection

Human papillomaviruses (HPVs) are well known for being linked to the development of cervical cancers, most of them being caused by the high-risk (HR) oncogenic genotypes, mainly 16 and 18. The efficacy of 2LPAPI® (Labo’Life), a micro-immunotherapy homeopathic drug, has been evaluated in HR-HPV infected women (n = 18), in a private gynecology practice, by comparing them to an untreated control group (n = 18). Patients were 20 to 45 years old and had cytology with Atypical Squamous Cells of Undetermined Significance (ASCUS) or Low grade Superficial Intra Lesions/ Cervical Intraepithelial Neoplasia Grade I (LSIL/CINI). Patients freely chose to be treated with the drug or not. Those deciding not to take the drug remained untreated and were followed as a control group. The drug was taken at the regimen of one capsule per day during 6 months. HR-HPV and cytology were evaluated at 6 and 12 months. After 12 months, HR-HPV was cleared in 78% of the patients taking the drug versus 44% in those not taking it (p = 0.086). In patients over 25 years, HR-HPV clearance in the treated group was significantly higher (81.3%) than in the control group (20%) (p = 0.004). The difference in the regression of the lesion grades almost reached statistical significance (p = 0.053). This follow-up confirms that the micro-immunotherapy drug 2LPAPI® is a safe and effective therapeutic approach to treat HR-HPV cervical lesions in women over 25 years.

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.

Human papillomavirus DNA and P16～(INK4A) expression in concurrent esophageal and gastric cardia cancers

AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expression.METHODS:Polymerase chain reaction was used to detect the presence of HPV type16 (HPV16).The expression of P16 INK4A protein was detected using immunohistochemistry.RESULTS:Among the CC specimens,HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA),respectively (47% vs 29%),and two of both ESCC and GCA.P16 INK4A was highly expressed in both ESCC and GCA.In the HPV-associated positive CC,higher P16 INK4A expression was observed in the GCA than in the ESCC (75% vs 25%,P < 0.05).CONCLUSION:HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA.P16 INK4A may be a screening index in the HPVassociated carcinoma of gastric cardia.