Detection of Human Papillomavirus DNA and E6/E7 mRNA from HPV Genotypes 16, 18, 31 and 33 in Histologically Confirmed Cases of Cervical Cancer and Precancerous Lesions in Burkina Faso

Introduction: Cervical cancer, caused by persistent high-risk human papillomavirus (HPV) infection, remains a global public health problem. The cellular transformation and maintenance of the malignant phenotype of these HPVs are attributed to the viral oncoproteins E6 and E7. Objective: This study aims to detect the presence of human papillomavirus DNA and E6/E7 oncoprotein mRNA of HPV genotypes 16, 18, 31 and 33 in cases of cervical cancer and precancerous lesions, histologically confirmed in Burkina Faso. Methods: This descriptive cross-sectional study focused on cases of cervical cancer and high-grade intraepithelial neoplasia (CIN) and was conducted from June to December 2022. One hundred (100) samples of fixed and paraffin-embedded tissues were collected from the pathological anatomy and cytology laboratories of hospitals in the capital of Burkina Faso. High-risk human papillomavirus (HR-HPV) DNA was detected using multiplex real-time PCR, while the presence of E6 and E7 mRNA in cervical cancer and high-grade CIN samples was determined using real-time Reverse Transcriptase-PCR (RT-PCR) with TaqMan probes. Results: The mean age of women diagnosed with cervical cancer and high-grade CIN was 50.81 ± 13.65 years, ranging from 22 to 82 years. Cervical cancer and high-grade CIN were positive for at least one high-risk human papillomavirus (HR-HPV) in 80% of cases. The most prevalent genotypes observed were HPV16, 18, 31, and 33, collectively accounting for 70.08% of cases. Of the 89 samples that tested positive for HR-HPV genotypes 16, 18, 31, and 33, 88 (98.88%;95% CI: [94.58 - 99.94]) were also positive for the presence of mRNA encoding the E6 and E7 oncoproteins of HPV16, 18, 31, and 33. Conclusion: In the presence of HPV DNA, testing for E6 and E7 oncoprotein mRNA could serve as a promising biomarker and valuable tool for improved assessment of the progression to cervical cancer.

Correlation of HPV infection with TLRs pathway activation and downstream gene expression in cervical precancerous lesions

Objective: To study the correlation of HPV infection with TLRs pathway activation and downstream gene expression in cervical precancerous lesions. Methods: Cervical precancerous lesion tissues from surgical resection or cone biopsy in Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University between June 2014 and May 2017 were collected and divided into HR-HPV positive group and HR-HPV negative group according to the condition of high-risk HPV infection;normal cervical tissues surgically removed due to fibroid in Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University during the same period were collected as the control group. The contents of TLRs pathway molecules as well as the expression of apoptosis-related genes and invasion-related genes in the cervical precancerous lesion tissues and normal cervical tissues were determined. Results:TLR2, TLR3, TLR4, TLR9 and NF-κB contents as well as CyclinD1, PCNA, iNOS, Gal-9, N-cadherin, HIF-1α and VEGF mRNA expression in HR-HPV positive group and HR-HPV negative group were significantly higher than those in control group whereas p53, Beclin1, LC3-II and SFRP2 mRNA expression were significantly lower than those in control group, and TLR2, TLR3, TLR4, TLR9 and NF-κB contents as well as CyclinD1, PCNA, iNOS, Gal-9, N-cadherin, HIF-1α and VEGF mRNA expression in HR-HPV positive group were significantly higher than those in HR-HPV negative group whereas p53, Beclin1, LC3-II and SFRP2 mRNA expression were significantly lower than those in HR-HPV negative group. Conclusion: HPV infection in cervical precancerous lesions can regulate downstream apoptosis and invasion gene expression by activating multiple TLRs pathways.

Comparison between peroral traction-assisted ESD and traditional ESD treatment for early gastric cancer and precancerous lesions

Objective:To explore the differences in the effect of peroral traction-assisted endoscopic submucosal dissection (ESD) and traditional ESD for the treatment of early gastric cancer and precancerous lesions. Methods:112 patients with early gastric cancer and precancerous lesions treated in our hospital between May 2013 and May 2016 were collected and divided into control group and observation group according to the random number table (n=56). Observation group of patients received peroral traction-assisted ESD, and the control group of patients only received traditional ESD. The intraoperative dissected lesion diameter, mean operation time and intraoperative blood loss of two groups of patients were recorded, enzyme-linked immunosorbent assay was used to detect serum inflammatory factor levels, and RIA was used to detect serum stress hormone levels. Results:Dissected lesion diameter of observation group was greater than that of control group (P<0.05) while mean operation time and intraoperative blood loss were less than those of control group (P<0.05);1 d after operation, serum inflammatory factors interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-12 (IL-12) and tumor necrosis factor-α(TNF-α) levels of observation group were lower than those of control group (P<0.05), and serum stress hormones cortisol (Cor),β-endorphin (β-EP), epinephrine (E), norepinephrine (NE) and angiotensin II (ATII) levels were lower than those of control group (P<0.05). Conclusions:Peroral traction-assisted ESD can effectively increase the lesion dissection effect and reduce the postoperative inflammatory response and stress response in patients with early gastric cancer and precancerous lesions.

Value of multi-quadrants biopsy:Pooled analysis of 11 population-based cervical cancer screening studies

Objective:The accuracy of colposcopy-guided biopsy is key to the success of colposcopic triage in cervical cancer screening programs.However,there is no widely adopted biopsy guideline up to date.Our study aimed to determine whether multi-quadrants biopsy improves the yield of cervical lesions.Methods:Eleven population-based cervical cancer screening studies were conducted in China.Cytology,highrisk human papillomavirus(hrHPV)testing and visual inspection were performed for primary screening.Females positive on one or more tests were referred for colposcopy and biopsy.The proportion of detected cervical intraepithelial neoplasia(CIN)2+and yields by quadrant lesion-targeted biopsy or 4-quadrant random biopsy were compared.Results:Among 4,923 females included,1,606 had quadrant lesion-targeted biopsy,and 3,317 had 4-quadrant random biopsy.The cumulative CIN2+yield increased from 0.10 for only one quadrant-targeted biopsy to 0.21,0.34,and 0.58 for at most two,three and four quadrants targeted biopsies.Among hrHPV positive females with high-grade squamous intraepithelial lesion(HSIL)+cytology,the cumulative CIN2+yield of a second targeted biopsy in another quadrant was significantly increased(P<0.05).Among hrHPV-negative females,the yield of 4-quadrant random biopsies was 0.005,and the yield by lesion-targeted biopsies was 0.017.For hrHPV positive females who had 4-quadrant random biopsy,the additional CIN2+yield for HSIL+,low-grade squamous intraepithelial lesion(LSIL)cytology,or abnormal visual inspection via acetic acid and Lugol’s iodine(VIA/VILI)were 0.46,0.11,0.14.Conclusions:A 4-quadrant random biopsy is recommended only for hrHPV positive females with HSIL cytology,and is acceptable if hrHPV positive with LSIL cytology or with abnormal VIA/VILI.Our findings add evidences for an objective and practical biopsy standard to guide colposcopy in cervical cancer screening programs in low-and middle-income countries.

Treatment of Precancerous Lesions of the Cervix of the Uterus by Leep: Experience of the Principal Clinic of the Togolese Association of Family Well-Being Planning Center (ATBEF)

Objectives: Describe the socio-demographic characteristics, describe the main indications for LEEP and present the main complications. Methodology: This was a cross-sectional and descriptive study with consecutive recruitment of the study population through cervical cancer screening campaigns throughout the country during the period July 1, 2017 to April 30, 2019. Included were all patients eligible for LEEP and having benefited from this therapeutic method during our study period. Data were collected from a registry and recorded on a questionnaire developed for this study. These data were analyzed using Epi info 3.5.1 software. The following parameters were studied: patient age, indication for LEEP, intraoperative and postoperative complications, histological examination of the specimens, and postoperative surveillance and screening follow-up one year after LEEP. Results: During the study period, 12,595 women were screened for precancerous cervical lesions. A total of 474 women had precancerous lesions. Of these women, 227 had undergone loop resection, a rate of 47.9%. The main indications for LEEP were extensive lesions (68.7%), lesions penetrating the internal cervical os (12.8%). Incidents occurred in 7.5% of patients during the procedure. Post-operative complications occurred in 14.7% of cases. Conclusion: LEEP is a better way to treat precancerous lesions but is not well known by medical staff. The equipment of health facilities and the training of medical staff will make it possible to popularize the practice throughout the country. This extension will contribute to the fight against cervical cancer.

Value of serum pepsinogen ratio screening for early gastric cancer and precancerous lesions in Youcheng area

BACKGROUND The 5-year survival rate of patients with advanced gastric cancer remains extremely low(<15%),whereas the 5-year survival rate of patients with early gastric cancer(EGC)is>90%.Consequently,strengthening the screening of patients with EGC and precancerous lesions(PCLs)is essential.AIM To identify the value of serum pepsinogen ratio(PGR)screening for EGC and PCLs in the Shengli Oilfield Central Hospital.METHODS We first selected 385 patients with gastric lesions in the Youcheng area,deter-mining benign lesions,PCLs,and EGC in 135,123,and 127 cases,respec-tively,based on endoscopy and case diagnosis.The positive rates of pepsinogen I,pep-sinogen II and Helicobacter pylori(H.pylori)in the three groups were detected,and the PGR was calculated.Subsequently,we plotted receiver operating charac-teristic curves to analyze the screening value of PGR and H.pylori-positive rates for PCLs and EGC.RESULTS PGR expression demonstrated a decreasing trend in patients with benign lesions,PCLs,and EGC successively according to the detection results,whereas the H.pylori-positive rate was notably increased in patients with PCLs and EGC compared to those with benign lesions.The area under the curves(AUCs)of PGR,H.pylori,and their combination in differentiating patients with benign lesions from those with PCLs were 0.611,0.582,and 0.689,respectively;PGR,H.pylori,and their combination had an AUC of 0.618,0.502,and 0.618 in distinguishing PCL patients from EGC patients,respectively;the AUCs of PGR,H.pylori,and their combination in discriminating patients with benign lesions from those with EGC were 0.708,0.581,and 0.750,respectively.CONCLUSION PGR has great screening potential for patients with EGC and PCLs in the Youcheng area,and the screening efficiency is further improved by combining the H.pylori-positive rate.

Cervical Cancer Screening, Adherence to and Challenges of Follow-Up in Resources Poor Setting

Background: Organized cervical cancer screening program has contributed to the reduction in incidence of cervical cancer in developed countries. Follow up, to ensure adherence to regular screenings, still poses challenges in poor resource settings. Objective: This study aims at determining the cervical cancer screening uptake, adherence to follow up instructions and interval cervical cancer screening and intervention to improve adherence through personalized reminders (phone calls and text messages). Methods: This was a prospective study of clients screened for cervical cancer at the University of Nigeria Teaching Hospital, Enugu from January 2012 to December 2016. The participants were studied for adherence to interval follow-up screening. Eligible participants were followed up using phone calls and text messages and the outcome noted. The data was analysed using statistical software for social sciences (SPSS) version 17. Results: The mean age and parity of 1146 participants screened for cervical intra-epithelial abnormalities within the study period was 44.18 ± 11.08 years and 3.78 ± 2.08 respectively. Most of the subjects (91.8%) screened negative to squamous intra-epithelial lesion (SIL) or malignancy, 8.2% (94/1146) had various grades of SIL. Thirty-five (37%), 29 (31%), 16 (17%) and 14 (15%) of the 94 SIL positive cases had atypical cells of unknown significance (ASCUS), low-grade squamous intra-epithelial lesion (LGSIL), high-grade squamous intra-epithelial lesion (HGSIL) and cervical carcinoma respectively. Adherence to instructions for repeat cytology was only 37.7% while that for 3 yearly interval rescreening was 17.5%. Phone calls and messages to clients improved adherence to appreciable extent. Conclusion: Adherence to interval and follow-up screening for cervical cancer was low. The use of phone calls and short message services (SMS) to remind clients of screening appointments increased adherence and should be employed in developing countries.

Identification of plasma proteomic signatures associated with the progression of cardia gastric cancer and precancerous lesions

Objective:Considering that there are no effective biomarkers for the screening of cardia gastric cancer(CGC),we developed a noninvasive diagnostic approach,employing data-independent acquisition(DIA)proteomics to identify candidate protein markers.Methods:Plasma samples were obtained from 40 subjects,10 each for CGC,cardia high-grade dysplasia(CHGD),cardia low-grade dysplasia(CLGD),and healthy controls.Proteomic profiles were obtained through liquid chromatography-mass spectrometry(LC-MS/MS-based DIA proteomics.Candidate plasma proteins were identified by weighted gene co-expression network analysis(WGCNA)combined with machine learning and further validated by the Human Protein Atlas(HPA)database.The area under the receiver operating characteristic curve(AUC)was used to evaluate the performance of the biomarker panel.Results:There was a clear distinction in proteomic features among CGC,CHGD,CLGD,and the healthy controls.According to the WGCNA,we found 42 positively associated and 164 inversely associated proteins related to CGC progression and demonstrated several canonical cancer-associated pathways.Combined with the results from random forests,LASSO regression,and immunohistochemical results from the HPA database,we identified three candidate proteins(GSTP1,CSRP1,and LY6G6F)that could together distinguish CLGD(AUC=0.91),CHGD(AUC=0.99)and CGC(AUC=0.98)from healthy controls with excellent accuracy.Conclusions:The panel of protein biomarkers showed promising diagnostic potential for CGC and precancerous lesions.Further validation and a larger-scale study are warranted to assess its potential clinical applications,suggesting a potential avenue for CGC prevention in the future.

Age-specific effectiveness of primary human papillomavirus screening versus cytology in a cervical cancer screening program: a nationwide cross-sectional study

Background:Primary human papillomavirus(HPV)screening is recommended for the detection of cervical intraepithelial neoplasia(CIN)in the general pop-ulation;however,the triage for HPV-positive women remains a challenge.This study aimed to evaluate the age-specific effectiveness of primary HPV screening versus primary cytology screening for identifying optimal strategies for women of different ages.Methods:The dataset of the prevalence round screening was derived from the National Cervical Cancer Screening Program in China.Primary cervical screen-ing protocols included cytology only,HPV testing with cytology triage,and HPV testing with HPV-16/18 genotyping plus cytology triage.The primary outcomes were age-specific detection rate,colposcopy referral rate and positive predictive value(PPV)for CIN2+.Multivariate Poisson regression was used to evaluate the relativeeffectivenessofHPVtestingandcytologyaccordingtoagegroups.TheI 2 statisticwitharandom-effectmodelwasusedtotesttheheterogeneityinrelative effectiveness of HPV testing versus cytology between age groups.Results:This study included 1,160,981 women.HPV testing with HPV-16/18 genotyping plus cytology triage significantly increased the CIN2+detection by 36%(rate ratio[RR]:1.36,95%confidential interval[CI]1.21–1.54)for women aged 35-44 years and by 34%(RR:1.34,95%CI 1.20-1.51)for women aged 45-54 years compared with cytology only.HPV testing with cytology triage had simi-lar CIN2+detection rate compared with cytology only.The PPVs were substan-tially increased for both HPV testing groups.Among women aged 55-64 years old,HPV testing with HPV-16/18 genotyping plus cytology triage increased the colposcopyreferralrateby19%(RR1.19,95%CI1.10-1.29)comparedwithcytology only,butdidnotincreasetheCIN2+detection(1.09,0.91–1.30).Theeffectiveness ofHPVtestingwithcytologytriagedidnotchangeinolderwomen.Thebetween-age-group heterogeneity in the effectiveness was statistically significant for HPV testing with HPV-16/18 genotyping plus cytology triage versus cytology only.Conclusions:Our results suggested that the effectiveness of primary HPV screeningwithdifferenttriagestrategiesdifferedamongagegroups.HPVtesting with HPV-16/18 genotyping plus cytology triage could be used for women aged 35-54 years to detect more lesions,and HPV testing with cytology triage could balance the CIN2+detection and the number of colposcopies for women aged 55-64 years.Longitudinal data including both prevalence and incidence screen-ing rounds are warranted to assess age-specific triage strategies.

Human papillomavirus distribution and cervical cancer epidemiological characteristics in rural population of Xinjiang,China

Background:Cervical cancer remains a major public health issue for the Uyghur women and other women living mainly in rural areas of Xinjiang.This study aims to investigate the distribution of human papillomavirus(HPV)infection and cervical cancer in rural areas of Xinjiang,China.Methods:Cervical cancer screening was performed on rural women aged 35 to 64 years from Xinjiang,China in 2017 through gynecological examination,vaginal discharge smear microscopy,cytology,and HPV testing.If necessary,colposcopy and biopsy were performed on women with suspicious or abnormal screening results.Results:Of the 216,754 women screened,15,518 received HPV testing.The HPV-positive rate was 6.75%(1047/15,518).Compared with the age 35-44 years group,the odds ratios(ORs)of HPV positivity in the age 45-54 years and 55-64 years groups were 1.18(95%confidence interval[Cl]:1.02-1.37)and 1.84(95%Cl:1.53-2.21),respectively.Compared with women with primary or lower education level,the ORs for HPV infection rates of women with high school and college education or above were 1.37(95%Cl:1.09-1.72)and 1.62(95%Cl:1.23-2.12),respectively.Uyghur women were less likely to have HPV infection than Han women,with an OR(95%Cl)of 0.78(0.61-0.99).The most prevalent HPV types among Xinjiang women were HPV 16(24.00%),HPV 33(12.70%),and HPV 52(11.80%).The detection rate of cervical intraepithelial neoplasia(CIN)2+was 0.14%and the early diagnosis rate of cervical cancer was 85.91%.The detection rates of vaginitis and cervicitis were 19.28%and 21.32%,respectively.Conclusions:The HPV infection rate in Xinjiang is low,but the detection rate of cervical cancer and precancerous lesions is higher than the national average level.Cervical cancer is a prominent public health problem in Xinjiang,especially in southern Xinjiang.

At-home cancer screening:a solution for China and other developing countries with a large population and limited number of healthcare practitioners

Five-year survival rate for patients with all cancers combined, in China, is only 30.9%, which is much lower than those in developed countries. The three main reasons for the low cancer curative rates in China include differences in the spectrum of cancer types, in early detection rates, and in the percentage of cancer patients receiving standardized treatment between China and developed countries.The most important mechanism for improving the curative rate is to improve early detection rates of major cancers in China using novel and affordable technologies that can be operated at home by the patients themselves.This attempt could be helpful in setting up a practical example for other developing countries with limited medical resources and a limited number of healthcare practitioners.

Magnifying chromoendoscopy combined with immunohistochemical staining for early diagnosis of gastric cancer

AIM:To assess the diagnostic value of using magnifying chromoendoscopy combined with immunohisto-chemical staining of proliferating cell nuclear antigen (PCNA)and p53 in the detection of gastric precancerous lesions. METHODS:Ninety-five patients who were treated for abdominal discomfort,abdominal pain,bloating,and acid reflux at our hospital from January 2010 to December 2011 were included in the study.An ordinary gastroscopic procedure was initially performed to select the lesions.All subjects underwent magnifying chromo-endoscopy to observe morphological changes of gastric pits.Biopsies were then taken from each area of interest and sent for pathological examination and detection of PCNA and p53 expression by immunohistochemistry. An immunoreactivity score for each lesion was calcu-lated.Based on immunoreactivity scores,immunohisto-chemical staining was then considered. RESULTS:Compared to intestinal metaplasia,gastric pits were more diverse in size,more irregular in shape, and more disorderly in arrangement in moderate and severe dysplasia.PCNA and p53 expression was sig-nificantly higher in precancerous lesions(intestinal metaplasia and dysplasia)than in chronic gastritis. PCNA expression showed an upward trend in types A-F pits.The number of cases that showed strong PCNA positivity increased significantly with an increase in the severity of lesions.Rank sum test for independent samples showed that p53 expression was significantly higher in types E and F pits than in types A-D pits(H =33.068,P=0.000).Rank sum test for independent samples showed that PCNA expression was significantly higher in types E and F pits than in types A-D pits(H =31.791,P=0.001). CONCLUSION:The presence of types E and F pits,in which p53 and PCNA are highly expressed,is highly sug- gestive of the occurrence of early cancer,and patients developing these changes should be closely followed.

Clinical significance of colposcopy on screening cervical intraepithelial neoplasia in cytological negative and smooth cervices

Objective： The aim of the study was to evaluate the clinical value of the video colposcopy in screening cervical intraepithelial neoplasia （CIN） in cytological negative and smooth cervices by optically gynecological examination. Methods： The 1050 women, whose cervices had been shown smooth and cytological negative by optical examine, were examined with electronic colposcopy in gynecological clinic, and biopsy was taken when the double abnormality of aceto-white epithelium and iodine negative, and other abnormal images were shown. A retrospective analysis of these cases was performed. Re. suits： （1） The 514 samples from 458 cases, including 458 samples of abnormal tissues under colposcopy and 56 samples of polyp or polypoid tumors by optically, were examined by biopsy. Among them, 68 samples were found to be CIN, including 11 cases of CINII/CINIII; （2） The 72 of 1050 cases showed the double-abnormality of aceto-white epithelium and iodine nega- tive. Among them, 64 cases were CIN determined by biopsy. And the positive predictive value of the double-abnormality of aceto-white epithelium and iodine negative under colposcopy was 88.9%, with a false negative rate of 3.3%; （3） Among 458 women examined by biopsy, only one of 350 samples from cervical polyp tissue was CIN （0.3%）, while 67 of 164 samples from the tissues with abnormal colposcopic images were found to be CIN （40.9%）, indicating the close relation between abnormal colposcopic findings and CIN; （4） The results of age-distribution analysis showed that, in the 164 cases with abnormal features under colposcopy, the incidence of double abnormality of aceto-white epithelium and iodine negative was higher in the age of sexual activity, just the same as the age distribution feature of CIN; while single abnormality of iodine negative appeared more in the age of over 50 years. Conclusion： Abnormal features displayed by colposcopy, especially the double abnormality of aceto-white epithelium and iodine negative, has an important significance for the screening of cervical precancerous lesions such as CIN. For this purpose, colposcopy examination is necessary even for the cases of cytological negative and smooth cervices.

Prevalence and Risk Factors of Cervical Neoplastic Lesions in Patients Attending a Healthcare Specialty Clinic, King Abdulaziz Medical City, Saudi Arabia

Background: Screening programs for cervical neoplasm among women in the Kingdom of Saudi Arabia (KSA) are very limited. Objective: To investigate the prevalence and risk factors of cervical epithelial abnormalities among patients attending a health care specialty center (HCSC) of King Abdulaziz Medical City, Riyadh, KSA. Design: A questionnaire was developed to collect information about socio-demographic variables followed by cytopathological analysis of Papanicolaou (Pap) smear. Settings: Female patients attending the gynecology clinic in the HCSC for cervical abnormalities during 2006 and 2008 were selected for the study. Subjects and Methods: Pap smear was collected and subjected to cytopathological analysis, which was further classified according to the revised Bethesda 2001 system. Information on socio-demographic variables, type and duration of oral contraceptives usage, active or passive smoking, history of sexually transmitted disease, or cervical cancer was collected by trained healthcare professionals. Results were analyzed using chi-square test and t-test. Main outcome measures: Lower frequency of cervical lesions among KSA females in comparison with the western countries. Results: A total of 495 Pap smears were studied, out of which 31 Pap smears were found to be unsatisfactory and therefore excluded. Among the remaining Pap smears, 6.5% were found to be abnormal;however, this was not statistically significant. None of the studied socio-demographic factors were found to be significantly correlated with the appearance of abnormal Pap smears, except for passive smoking. Conclusion: Saudi Arabia had a lower frequency of cervical lesions in comparison with the western countries. Further, this study can serve as a pilot study for a larger national screening program for the identification of prevalence and risk factors of cervical lesions in the women of KSA. Limitations: Cases included in the study belong to the particular period, and patients with abnormal Pap smears were not followed up. In-extension, the included data were not restricted for a particular community.

Screening for Oral Cancer 2018

In Hungary, the incidence and mortality from oral cancer is so high, that in the past decades it has attracted international attention. The mortality rates are the highest in Europe. As risk factors, smoking and alcohol drinking have a multiplicative role;in addition, a number of dental factors also play a role. Premalignant conditions and lesions are well known. They should be targeted for early detection and early treatment. The screening tool is simple: inspection and palpation. The physician-patient encounters provide opportunity for screening. This paper looks for the answer to the long debated question: who is responsible for oral screening?

Identifying high-risk individuals for gastric cancer surveillance from western and eastern perspectives: Lessons to learn and possibility to develop an integrated approach for daily practice

Current evidence shows that individuals with gastric dysplasia, severe and extensive gastric atrophy, extensive gastric intestinal metaplasia and the incomplete subtype of intestinal metaplasia are at high risk for gastric cancer(GC) development. There are several approaches to identifying these subjects,including noninvasive methods, esophagogastroduodenoscopy and histology.The main approach in Western countries is histology-based while that in Eastern countries with a high prevalence of GC is endoscopy-based. Regarding asymptomatic individuals, the key issues in selecting applicable approaches are the ability to reduce GC mortality and the cost-effectiveness of the approach. At present, population-based screening programs have only been applied in a few Asian countries with a high risk of GC. Pre-endoscopic risk assessment based on demographic and clinical features, such as ethnicity, age, gender, smoking and Helicobacter pylori status, is helpful for identifying subjects with high pre-test probability for a possibly cost-effective approach, especially in intermediate-and low-risk countries. Regarding symptomatic patients with indications for esophagogastroduodenoscopy, the importance of opportunistic screening should be emphasized. The combination of endoscopic and histological approaches should always be considered as endoscopy provides a real-time assessment of the patient’s risk level. In addition, imaging enhanced endoscopy(IEE) has been shown to facilitate targeted biopsies resulting in better correlation between endoscopic and histological findings. Currently, the use of IEE is recommended for endoscopic examinations, and the Operative Link for Gastric Intestinal Metaplasia or Operative Link on Gastritis Assessment grading systems are recommended for histological examinations whenever available. However,resource limitations are an important barrier in many regions worldwide. Thus,for an approach to be applicable in real-life practice, it should be not only evidence-based but also resource-sensitive. In this review, we discuss the current understanding and approaches to identifying high-risk individuals from western and eastern perspectives, as well as the possibility of an integrated, resourcesensitive approach.

NATURAL HISTORY OBSERVATION FOR ESOPHAGEAL AND CARDIA PRECURSORS BY REPETITIVE ENDOSCOPIC SCREENING OF 301 SUBJECTS IN SHEXIAN

OBJECTIVE To investigate the natural history of fast developing esophageal and cardia precursors.METHODS Repetitive endoscopic screenings were performed among 40-69-year-olds in the high-incidence areas for esophageal cancer in Shexian. RESULTS The initial diagnosis and the lag-time for 7 subsequently identified severe dysplasia （SD） subjects were as follows： in one subject 13 months after a baseline diagnosis of normal epithelium, in another subject 7 months after a baseline diagnosis of base cell hyperplasia （BCH）, in four subjects 3, 4, 4, and 10.5 months after baseline diagnosis of mild dysplasia （mD）, and in one subject 12.5 months after a baseline diagnosis of moderate dysplasia （MD）. The initial diagnosis and the lag-time for 6 subsequently identified carcinomas in situ or intramucosal carcinoma cases were： in one case 48 months after a baseline diagnosis of mD, in 2 cases 4 and 13 months after baseline diagnoses of MD, and in the other 3 cases 3.5, 9, and 17.5 months after baseline diagnoses of SD. The initial diagnosis and lag-time for 3 subsequently identified invasive cancer cases, were： in one case 50 months after a baseline diagnosis of MD, in 2 cases 14 and 19 months after baseline diagnoses of SD. In addition, during a 4-year-follow-up of 18 subjects after endoscopic mucosa resection, 9 of them were found to have developed precursors again at other sites, and also additional findings were obtained for 11 of the 16 dysplasia cases by repetitive biopsy in less than 2 months after the initial endoscopy. CONCLUSION A 5-year screening interval for BCH and mD, and a 3-year interval for MD may be too long for the fast developing precursors. Periodic screenings with shorter intervals should be considered to control the number of interval cases due to fast development, multifocal carcinogenesis, and false negative results inherent in one-time endoscopic biopsy sampling.

Relationship between the high-risk HPV infection and the expression of oncogenes, anti-oncogenes in cervical dysplasia

Objective:To study the relationship between the infection of high-risk HPV in cervical precancerous lesion and the expression of oncogene, anti-oncogene.Methods:218 cases ofcervical intraepithelial neoplasia patients in our hospital during May 2014–May 2016 were chosed and divided into high-risk HPV group (n=107), low-risk HPV group (n=111) according to cervical tissue HPV test;another 100 cases of patients received cervical biopsy and confirmed as benign lesions were enrolled in the control group. RT-PCR method was used to detect the mRNA expression of proto-oncogene and anti-oncogene in three groups, Western-blot method was used to detect the protein expression of Sox-2 and Wnt/β-catenin signal pathway.Results: mRNA expression of oncogene DEK, Bmi-1, c-fos, K-ras, Prdx4 in high-risk HPV group were higher than low-risk HPV group and control group (P<0.05);mRNA expression of anti-oncogene P27, P16, DAPK, PTEN, eIF4E3 in high-risk HPV group were lower than low-risk HPV group and control group (P<0.05);expression of Sox-2 and Wnt/β-catenin signaling pathway protein Sox-2,β-catenin, wnt-1, wnt-3a in high-risk HPV group were higher than low-risk HPV group and control group (P<0.05).Conclusions:High-risk HPV infection can increase the expression of oncogenes and reduce the expression of anti-oncogenes in cervical dysplasia tissues on Sox-2- and Wnt/β-catenin signaling pathway manners.

细胞角蛋白7在宫颈癌及癌前病变中的表达及临床意义

目的 探究细胞角蛋白7 (cytokeratin7,CK7)在宫颈癌及癌前病变中的表达及临床意义。方法 选取2017年1月至2023年4月在甘肃省妇幼保健院就诊疑似宫颈病变患者的存档病理蜡块及其相关的病历资料,其中包括正常宫颈鳞状上皮100例(正常组)、宫颈鳞癌100例(宫颈鳞癌组)、宫颈低级别鳞状上皮内病变(low-grade squamous intraepithelial lesions,LSIL) 100例(LSIL组)、宫颈高级别鳞状上皮内病变(high-grade squamous intraepithelial lesions,HSIL) 100例(HSIL组)、宫颈腺癌50例(宫颈腺癌组)。使用免疫组织化学方法检测各组p16、Ki-67和CK7的表达情况,分析其对宫颈癌与癌前病变的诊断价值和对LSIL与HSIL的鉴别价值,并比较宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ级及CINⅢ级、高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)感染及非感染患者的p16、Ki-67和CK7表达情况。结果 五组p16、Ki-67和CK7阳性表达率比较差异均有统计学意义(均P<0.05);宫颈鳞癌组、宫颈腺癌组、HSIL组、LSIL组的p16、Ki-67和CK7阳性表达率均显著高于正常组(均P<0.05),宫颈鳞癌组、宫颈腺癌组的p16、Ki-67和CK7阳性表达率均显著高于HSIL组、LSIL组(均P<0.05),HSIL组的p16、Ki-67和CK7阳性表达率均显著高于LSIL组(均P<0.05);p16、Ki-67和CK7表达联合检测诊断宫颈癌及癌前病变的曲线下面积(the area under curve,AUC)均显著大于各指标单独检测(均P<0.05)。p16、Ki-67和CK7表达联合检测鉴别LSIL与HSIL的AUC均显著大于各指标单独检测(均P<0.05);CINⅡ级和CINⅢ级患者的p16、Ki-67和CK7阳性表达率比较差异均无统计学意义(均P>0.05);HR-HPV感染组的p16、Ki-67和CK7阳性表达率均显著高于非感染组(均P<0.05)。结论 CK7在宫颈癌及癌前病变患者中多呈现阳性表达现象,其与p16、Ki-67联合检测对宫颈癌及癌前病变具有诊断价值,且HR-HPV感染可促进CK7阳性表达。

血清MG7-Ag水平检测与新型胃癌评分系统在胃癌高危人群风险评估中的价值

目的:研究血清MG7-Ag与新型胃癌评分系统在胃癌高危人群风险评估中的临床价值。方法:纳入2021年1月至2022年12月在本院接受胃镜检查及活检的163例胃癌癌前病变患者和42例胃癌患者作为研究对象。收集一般资料,包括年龄、性别、血清幽门螺杆菌抗体(呼气试验C13/C14)、胃蛋白酶原I/胃蛋白酶原II比值(PGR)、胃泌素17(G17)、内镜检查及病理诊断结果:根据新型胃癌筛查评分系统将入组患者分为低危组、中危组、高危组,采用酶联免疫吸附法进行MG7-Ag检测,分析影响胃癌诊断的影响因素,评价MG7-Ag和新型胃癌评分系统在胃癌高危人群风险评估中的价值。结果:胃癌癌前病变和胃癌组患者一般资料差异无统计学意义,具有可比性。所有205例患者中,新型胃癌评分系统分为高危34例、中危63例和低危108例,其中胃癌检出率分别为24(73.53%)例、13(20.63%)例、5(4.63%)例。以MG7-Ag表达的中位数分为高表达组和低表达组,其中高表达组41例、低表达组164例,其中胃癌检出率分别为33(80.49%)例、9(5.49%)例。单因素和多因素分析显示,新型胃癌评分系统和MG7-Ag检测均为影响胃癌诊断的影响因素之一。通过ROC曲线分析新型胃癌评分系统和MG7-Ag检测在癌前病变和胃癌中的诊断价值,结果显示,新型胃癌评分系统的曲线下面积(AUC)为0.71(95%CI:0.65~0.74),MG7-Ag检测的AUC为0.78(95%CI:0.75~0.80),两者联合诊断的AUC为0.86(95%CI:0.81~0.90),两者联合诊断的价值明显优于单独诊断。结论:血清MG7-Ag与新型胃癌评分系统联合诊断在筛选胃癌高危人群中的价值明显优于单独检测,对未来胃癌癌前病变和胃癌的诊断具有很高的临床指导价值。