Radical Hysterectomy in Cervical Cancer: Patients’ Epidemiological and Clinical Profiles and Perioperative Outcome in Two Referral Hospitals in Cameroon

Background: Cervical cancer (CC) is one of the most frequent cancers and the leading cause of death from gynecological cancer in Low and middle income countries, Cameroon inclusive. Surgery is the primary treatment modality when the disease is diagnosed at early stage. Radical hysterectomy in cervical cancer has not been evaluated in recent years in Cameroon. The purpose of this study is thus to evaluate the epidemiological and clinical features and short term outcomes of patients who underwent surgery. Patients and methods: This retrospective study was conducted at the Douala Gynaeco-obstetric and Pediatric Hospital and the Douala General Hospital. Cervical cancer patients who underwent Radical hysterectomy between January 2015 and December 2020 were included. A pre-established data collection tool was used to record socio-demographic, clinical and outcomes information from patients’ files;additional outcome information was obtained from phone calls. Descriptive analysis was done using the SPSS version 26. Bivariate analysis was used to determine associations between disease and patients characteristics and occurrence of adverse postoperative outcome. P value of 0.05 was considered. Results: Sixty one patients were enrolled. Their ages ranged from 33 to 74 years with a mean age of 51.95 ± 10.29 years. Over 85% of women were married, 65.57% were unemployed and 86.88% were multiparous. Only 28% had never done cervical cancer screening. Most patients had stage IB1 to IB2 stage disease (57.1%). Less than 9% underwent radical hysterectomy and 8 of those (13.11%) suffered intraoperative complications. Twenty-five patients (40.98%) presented immediate and short term complications. There was no significant association between the disease or patients’ characteristics and adverse outcomes. Conclusion: Cervical cancer patients are relatively young in our settings and only 9% of them reach the hospital at early stage. Postoperative adverse outcomes rate is higher than that reported in the literature. Sensitization on screening and awareness of early symptoms can reverse the situation.

Prevalence of HPV Infection And Cervical Intraepithelial Neoplasia And Attitudes towards HPV Vaccination among Chinese Women Aged 18-25 in Jiangsu Province

Objective：Few data are available on the epidemiology of HPV and cervical cancer among Chinese women younger than 25 years old.This study aimed to estimate the HPV infection rate and the prevalence of cervical intraepithelial neoplasia（CIN） in women aged 18-25,as well as their knowledge of and attitudes towards HPV vaccination.Methods：A population-based cervical cancer screening study was conducted on women aged 18-25 in Jiangsu province in 2008.Participants provided socio-demographic,reproductive and behavioral information and completed a survey about their knowledge of and attitudes towards HPV vaccination.Women then underwent a gynecologic exam to provide two cervical exfoliated cell samples for high risk HPV DNA testing and liquid-based cytology（LBC） as well as visual inspection with acetic acid（VIA）.Women testing positive for any test were referred to colposcopy and biopsy.The gold standard for diagnosis of cervical lesions was directed or random biopsies.Results：Within the sample of 316 women,3.4% of them were diagnosed with CIN grade 2 or worse lesions and 17.1% were found to be positive for HPV DNA.Among these young women,extra-marital sexual behavior of them（OR=2.0,95%CI：1.1-3.8） or their husbands（OR=2.6,95%：1.4-4.7） were associated with an increased risk of HPV positivity.Although overall HPV awareness was low,after a brief educational intervention,98.4% reported they would electively receive HPV vaccination and would also recommend that their daughters be vaccinated.However,most urban and rural women reported their ideal maximum out-of-pocket contribution for HPV vaccination to be less than 500 RMB and 50-100 RMB,respectively.Conclusion：Our study indicates cervical disease burden is relatively high among sampled Chinese women aged 18-25.Appropriate educational interventions for female adolescents and strategies to subsidize vaccine costs are definitely needed to ensure the effectiveness of vaccination campaigns in China.

Risk assessment and triage strategy of cervical cancer primary screening on HPV integration status:5-year follow-up of a prospective cohort study

Objective:We investigated the relation between man papillomavirus(HPV)integration status and the immediate risk of cervical intraepithelial neoplasia(CIN),as well as the triage strategy based on HPV integration test.Methods:4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective,population-based,clinical observational study to evaluate the triage performance of HPV integration.Cervical exfoliated cells were collected for HPV testing and cytologic test.If high-risk HPV was positive,HPV integration test was performed at baseline,2-year and 5-year follow-up.Results:At baseline,HPV integration was positively correlated with the severity of cervical pathology,ranging from 5.0%(15/301)in normal diagnosis,6.9%(4/58)in CIN1,31.0%(9/29)in CIN2,70%(14/20)in CIN3,and 100%(2/2)in cervical cancer(P<0.001).Compared with cytology,HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+,higher specificity(92.8%[90.2%-95.4%]vs.75.5%[71.2%-79.8%],P<0.001)and higher positive predictive value(36.4%[22.1%-50.6%]vs.15.2%[8.5%-21.8%],P<0.001).HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy(10.7%[44/410]vs.27.3%[112/410],P<0.001).The HPV integration-negative group exhibited the lowest immediate risk for CIN3+(1.6%)and accounted for the largest proportion of the total population(89.3%),when compared with the normal cytology group(risk,1.7%;proportion,72.7%).Conclusion:As a key molecular basis for the development of cervical cancer,HPV integration might be a promising triage strategy for HPV-positive patients.

Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes incervical in traepithelial neoplasia and cervical cancer

The chemokine CXCL12 is highly expressed in gynecologic tumors and is widely known to play a biologically relevant role in tumor growth and spread. Recent evidence suggests that CXCL16, a novel chemokine, is overexpressed in inflammation-associated tumors and mediates pro-tumorigenic effects of inflammation in prostate cancer. We therefore analyzed the expression of CXCL12 and CXCL16 and their respective receptors CXCR4 and CXCR6 in cervical intraepithelial neoplasia (CIN) and cervical cancer and further assessed their association with clinicopathologic features and outcomes. Tissue chip technology and immunohistochemistry were used to analyze the expression of CXCL12, CXCR4, CXCL16, and CXCR6 in healthy cervical tissue (21 cases), CIN (65 cases), and cervical carcinoma (60 cases). The association of protein expression with clinicopathologic features and overall survival was analyzed. These four proteins were clearly detected in membrane and cytoplasm of neoplastic epithelial cells, and their distribution and intensity of expression increased as neoplastic lesions progressed through CIN1, CIN2, and CIN3 to invasive cancer. Furthermore, the expression of CXCR4 was associated significantly with the histologic grade of cervical carcinoma, whereas the expression of CXCR6 was associated significantly with lymph node metastasis. In Kaplan-Meier analysis, patients with high CXCR6 expression had significantly shorter overall survival than did those with low CXCR6 expression. The elevated co-expression levels of CXCL12/CXCR4 and CXCL16/CXCR6 in CIN and cervical carcinoma suggest a durative process in cervical carcinoma development. Moreover, CXCR6 may be useful as a biomarker and a valuable prognostic factor for cervical cancer.

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.

Pathological characteristics and immunophenotype analysis of cervical intraepithelial neoplasia

Objective To explore the clinical pathological features and immunophenotypes of cervical intraepithelial neoplasia(CIN).Methods The protein expression of p16, p53, Bcl-2, and c-erb B-2 in 59 cases of CIN, 20 cases of cervical squamous cell carcinoma, and 20 cases of normal cervical tissues were tested using immunohistochemistry staining.Results The expression rates of p16, p53, Bcl-2, and c-erb B-2 in CIN tissues were 76.3%(45/59), 28.85(17/59), 61.0%(36/59), and 40.0%(23/59), respectively. The expression rates of p16, p53, Bcl-2, and c-erb B-2 in cervical squamous cell carcinoma tissues were 60.0%(12/20), 60.0%(12/20), 75.0%(15/20), and 65.0%(13/20), respectively. The expression rates of p16, p53, Bcl-2, and c-erb B-2 in normal cervical tissues were 0.0%(0/20), 0.0%(0/20), 35.0%(7/20), 0.0%(0/20), respectively. In comparison to normal tissues, the differential expressions of p16, p53, and Bcl-2 in squamous cell carcinoma and CIN were statistically significant(P <0.001), whereas the difference between the squamous cell carcinoma and CIN was not significant(P >0.05). In comparison to normal tissues, the differential expressions of c-erb B-2 and p53 in squamous cell carcinoma and CIN were statistically significant(P >0.05). The differential expressions of Bcl-2, c-erb B-2, and p53 in CIN 3 were statistically significant in comparison to CIN 1 and CIN 2(P <0.05). Conclusion Overexpression of Bcl-2 occurs early in the development of cervical cancer, whereas p16 and c-erb B-2 overexpression are markers for cell malignancy. The expression of p53 is correlated with the development of cervical cancer.

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.

Efficacy and Tolerability of Thermocoagulation Treatment of High-Grade Cervical Intraepithelial Neoplasia

Purpose: Cervical cancer is still one of the main causes of cancer and mortality in women, especially in low- and middle-income countries, although it is a completely preventable disease through the detection and treatment of pre-cancer lesions. We evaluated the efficacy and tolerability of thermocoagulation treatment of high-grade cervical intraepithelial neoplasia (CIN 2 and 3). Methods: We evaluated 115 women with high-grade cervical intraepithelial neoplasia, 54 with CIN 2 and 61 with CIN 3, confirmed by biopsy and without previous treatment, from January 2016 to December 2018, undergoing thermocoagulation treatment at the Lower Genital Tract Pathology and Colposcopy Service of the Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. Results: The mean age was 33.11 years (SD = 9.83) for CIN 2 and 35.28 years (SD = 7.97) for CIN 3 patients. Treatment efficacy was 90.8% in CIN 2 and 94.9% in CIN 3 cases. Pain was the main symptom reported at the time of treatment, occurring more frequently in the CIN 3 group (49.1% versus 27.8% in the CIN 2 group). As the more important long-term complication, there were 3 cases of pelvic inflammatory disease in CIN 2 (5.6%) and 3 in CIN 3 group (5.0%). The percentage of residual lesion was very low in both groups, 5 in CIN 2 group (9.2%) and 2 in CIN 3 group (3.4%). Conclusion: Thermocoagulation is an effective method for the treatment of cervical pre-cancer lesions (CIN 2 and CIN 3), with a low risk of adverse events and complications.

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.

Management of Cervical Intra Epithelial Neoplasia by Loop Electrosurgical Excision Procedure in a Low Resource Country: An Experience from the YaoundéGeneral Hospital, Cameroon

Background: Cervical cancer is the third most common cancer worldwide, and 80% of cases occur in the developing world. A critical component of effective cervical cancer screening programs is the ability to offer women appropriate and effective treatment for cervical intra epithelial neoplasia (CIN). Objectives: This study aimed at assessing the primary experience of management of CIN by Loop Electrosurgical Excision Procedure (LEEP) in a low resource country. Methods: We carried out a descriptive cross sectional study at the Yaoundé General Hospital in Cameroon. Results: Twenty three cases of CIN were treated by LEEP. Mean age of patients was 40.5 ± 9.9 years. Six (26.1%) patients were infected by the Human Immunodeficiency Virus (HIV). LEEP was indicated in 21 (91.30%) cases for CIN2 and CIN3. The mean duration of the surgical procedure was 10 ± 3 minutes. There was one (4.3%) complication (persistent cervical bleeding). Surgical margins were negative for dysplasia or invasive carcinoma in 18 (78.26%) cases and non-applicable in 5 (21.73%) cases (thermal artefacts of margins and cervicitis without CIN). One patient with micro invasive carcinoma on post-operative histology was treated by total hysterectomy. Cervical cytology was normal at 6 months post LEEP for 15 cases out of 16 (93.8%) patients who performed the test. One woman achieved pregnancy and delivered a term baby. Conclusion: Treatment of CIN by LEEP is feasible, safe and effective in our setting.

Improved Detection of Cervical Cancer and High Grade Neoplastic Lesions by a Combination of Conventional Cytology and DNA Automated Image Cytometer

OBJECTIVE: To reduce false-negative rates of population based cervical screening programs employing conventional cytology in combination with automated DNA image cytometer. METHODS: Involved cervical samples from a total of 3603 women were taken by a cervix brush and then placed into a fixative solution. The cells were separated from mucus by mechanical and chemical treatment after which they were deposited onto microscope slides by a cytospin. Two slides were prepared from each case;one slide was stained by Papanicolaou stain for conventional cytology examination, while the other slide was stained by a DNA specific and stoichiometric stain. The latter slide was used to determine the relative amount of DNA in the cell nuclei in order to assess the ploidy status of the epithelial cells. Enrolled in the study, 157 women were followed by colposcopy examination where punch biopsies were taken from the visible lesions or from suspicious areas. The results of the conventional cytology were then compared to the DNA image cytometer for all samples. RESULTS: Histopathology diagnosed 51 lesions from the 132 biopsied cases as CIN2 or higher, including 27 CIN2, 16 CIN3 and 8 invasive cancers. Conventional cytology correctly identified 29 of the 51 high grade CIN and in-vasive cancer, while DNA image cytometer correctly identified 38 high grade CIN and invasive cancer using the crite-rion that at least three cells were found on the slide that contained DNA amount in excess of 5c. 42 out of 51 high grade CIN and invasive cancer were found by conventional cytology in combination with DNA image cytometer. Sensitivities were 56.8%, 74.5% and 82.4%, while specificities were 86.2%, 81.5% and 81.5% in conventional cytology, DNA image cytometer and combination both cytology and DNA image cytometer respectively. CONCLUSION: The study demon-strated that screening for high grade neoplastic lesions and cervical cancer by DNA image cytometer or combination of conventional cytology and DNA image cytometer is more sensitive than conventional screening approach.

Twist and YB-1 gene expression in cervical cancer and precancerous tissue and their correlation with cell invasion

Objective:To study the correlation of Twist and YB-1 gene expression in cervical cancer and precancerous tissue with cell invasion.Methods:Cervical cancer tissue, precancerous tissue and normal cervical tissue surgically removed in our hospital between May 2013 and April 2015 were collected;immunohistochemical staining kits were used to detect the positive protein expression rate of Twist and YB-1 gene;fluorescence quantitative PCR kits were used to detect Twist, YB-1 and invasion gene mRNA expression.Results:Twist and YB-1 mRNA expression and positive protein expression rate as well as USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue and precancerous tissue were significantly higher than those in normal cervical tissue, Twist and YB-1 mRNA expression and positive protein expression rate as well as USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue were significantly higher than those in precancerous tissue;USP22, Rab11, Rac1 and ANXA5 mRNA expression in cervical cancer tissue and precancerous tissue with positive Twist and YB-1 expression were significantly higher than those in cervical cancer tissue and precancerous tissue with negative Twist and YB-1 expression.Conclusion:Highly expressed Twist and YB-1 in cervical cancer and precancerous tissue can promote cell invasion.

Screening of premalignant and malignant cervical lesions in underdeveloped countries by using Pap smear as routine investigation in outpatient department

Objective: Papanicolou (Pap) smear screening has dramatically reduced the incidence of invasive cervical cancer worldwide. Pap smear screening is still not widely available in developing countries and therefore cannot be used as mass screening tool. This study was designed to establish the role of Pap smear as a routine investigation for females presented to gynecological department. Methods: It was a hospital based study. Patients attending with complaints including irregular vaginal bleeding, vagina discharge, dyspareunia, low backache or lower abdominal pain and primary or secondary infertility were included in the study. All these patients underwent pap smear. Results: Age of females was 25 to 60 years. Ninety females had dysplasia. Mild to moderate dysplasia was positive in 84 females. Six patients had severe dysplasia suspicious for squamous cell carcinoma (SCC) which was confirmed as invasive SCC on biopsy. All patients with mild to moderate dysplasia were regularly followed at 4 to 6 months. Thirty patients were lost during follow up. Forty had negative smear at 6 months, while fourteen having persistent dysplasia on repeated pap smears were referred for biopsies. Histopathology confirmed invasive SCC in five patients while chronic cervicitis was reported in nine patients. Only two of screened patients with high suspicion for cancer showed false negative results. Directed biopsies done in these confirmed invasive SCC. Conclusion: Pap smear is a useful, simple, non-invasive and reliable screening tool for cervical cancer. It may be practiced as a routine investigation in outpatients in developing countries, where mass screening is not available.

Clinical Outcome of Topical Interferon Alpha-2b Cream in Phase II Trial for LSIL/CIN 1 Patients

Objectives: Interferon alpha-2b possesses variable activity against human papillomavirus (HPV) associated cervical intraepithelial neoplasia (CIN). No topical therapy is currently available for treatment of early stage CIN. We evaluated a new patented drug delivery technology in order to achieve topical efficacy. Methods: Two separate studies were conducted in parallel. IFN002 (treatment group) was an open label study. Twenty patients with Pap IIW, III and IIID (CIN1) were treated with intravaginal application of Interferon alpha-2b cream (5 g, 2 MIU/g) three times a week (alternate days) for 6 weeks with 6 weeks of follow up to determine its effect on cytologic and colposcopic assessment. HPV001 (control group) was a 12 week observational study. Both studies had similar inclusion/exclusion criteria and patient population. Results: In IFN002, 8 of 20 patients (40%) in the ITT population showed resolution of abnormal Pap smear during the 12 weeks following start of treatment (responders). In HPV001, 7 of 21 patients (33.3%) were regressors (p = 0.45, one-sided FET). In the PP population, 7 of 12 (58.3%) patients in IFN002 were regressors com-pared to 7 regressors of 19 patients (36.8%) in HPV001 patients (p = 0.21, one-sided FET). Among patients with Pap IIID, 8 of 14 patients in IFN002 showed resolution of abnormal Pap smear, while 4 of 14 patients resolved in HPV001 (one-sided FET, p = 0.13). Conclusions: Interferon alpha-2b cream (5 g, 2 MIU/g) may be an effective treatment for CIN 1 patients, and future investigation is warranted.

乌鲁木齐市11654例女性HPV分型及定量检测结果分析

目的分析新疆乌鲁木齐市女性人乳头瘤病毒(HPV)感染特点及HPV分型定量检测对宫颈病变的预测性能。方法收集2022年1-12月于新疆医科大学第一附属医院妇科就诊并进行HPV检测的11654例女性的HPV检测结果。根据年龄将所有就诊者分为低龄组(≤29岁)、青龄组(>29~39岁)、中龄组(>39~49岁)、中老龄组(>49~59岁)和老龄组(>59岁)。其中1483例患者同时进行阴道镜活检和宫颈组织病理学检测,根据组织病理学诊断结果,将1483例患者分为宫颈炎、宫颈上皮内瘤变(CIN)Ⅰ、CINⅡ、CINⅢ和宫颈癌,将CINⅠ及以上命名为CIN阳性,CINⅡ及以上命名为CINⅡ+,CINⅢ及以上命名为CINⅢ+。采用实时荧光定量PCR检测HPV亚型及病毒载量,比较不同民族、年龄、宫颈疾病女性HPV的检测结果,比较不同宫颈病变患者主要的HPV亚型病毒载量水平,采用受试者工作特征(ROC)曲线确定主要的HPV亚型预测CINⅡ+的病毒载量阈值。结果在11654例就诊者中,HPV感染率为30.60%,单一亚型感染占77.73%。HPV16、52、58是CIN阳性患者感染的主要型别,分别占38.89%、14.90%、11.11%。汉族、维吾尔族、回族和哈萨克族女性HPV感染率分别为31.89%、24.39%、31.76%和27.88%,4个民族HPV感染率比较,差异有统计学意义(χ^(2)=40.929,P<0.001)。在11654例就诊者中,老龄组HPV感染率最高(34.04%),中龄组HPV感染率最低(26.41%),不同年龄组间HPV感染率比较,差异有统计学意义(χ^(2)=37.754,P<0.001)。在396例CIN阳性患者中,高危型HPV和单一亚型感染率随CIN级别升高而升高(χ^(2)趋势=9.994、7.233,P<0.01)。CINⅡ+患者HPV16、52、58病毒载量与宫颈炎患者相比,差异均有统计学意义(P<0.05);且HPV16、52、58病毒载量预测CINⅡ+的最佳截断值分别为4.382、3.694、4.114 copy/104个细胞(经lg转化)。结论新疆乌鲁木齐市女性HPV感染以单一亚型感染为主,HPV16、52、58是主要的感染型别,并且HPV标准化定量具有作为宫颈高级病变预测标志物的潜力。

血清HE4、LH、FSH对宫颈癌和宫颈上皮内瘤变的鉴别诊断价值

目的探究血清人附睾蛋白4(HE4)、促黄体生成素(LH)、卵泡刺激素(FSH)对宫颈癌和宫颈上皮内瘤变(CIN)的鉴别诊断价值。方法选择89例接受宫颈癌筛查的宫颈病变患者,经病理学或细胞学明确诊断宫颈癌51例、CIN 38例,检测所有患者血清HE4、LH、FSH水平,分析宫颈癌患者与CIN患者血清检测指标水平差异,采用受试者特征工作曲线(ROC曲线)、二元logistics回归分析法评价HE4、LH、FSH在疾病鉴别中的价值。结果宫颈癌患者血清HE4、LH、FSH水平均显著高于CIN患者(P<0.05);宫颈病变患者血清HE4与LH、FSH水平呈正相关(γ=0.357、0.392,P<0.05)。ROC曲线分析显示,血清HE4、LH、FSH诊断宫颈癌的敏感性均较低,三者联合诊断效能较单一指标更高,联合诊断曲线下面积为0.859,诊断敏感度88.24%、特异度71.05%;logistics回归分析显示,HE4>62.84 pmol/ml是宫颈癌发病的影响因素(P<0.05)。结论宫颈癌患者血清HE4、LH、FSH水平异常升高,且指标间呈正相关,三者联合用于鉴别诊断宫颈癌和CIN具有一定临床价值。

子宫颈高危型人乳头瘤病毒感染的中西医治疗研究进展

宫颈癌是我国女性第6位高发恶性肿瘤,严重危害女性生命健康,而子宫颈高危型人乳头瘤病毒(HPV)的持续感染是诱发宫颈癌及宫颈上皮内瘤样病变(CIN)的主要因素。由于从病毒感染进展为宫颈癌需要较长时间,针对病因,及时阻断子宫颈高危型HPV感染,有效阻止病情进展,防止宫颈癌的发生尤为重要。西医外用药物、消融及手术治疗存在易复发、出血、感染及术后影响生育功能等并发症,中医辨证论治,在病情不同阶段均可提供有效干预,且中药多靶点,与多个信号通路发生作用,与西医协同治疗可优势互补,提高疗效。通过综述中西医治疗子宫颈高危型HPV的主要方法,为该病临床诊治提供思路,同时综述子宫颈高危型HPV感染实验模型及中医药抗高危型HPV感染作用机制,为进一步实验研究提供参考。

人乳头瘤病毒感染情况、阴道微环境指标与宫颈病变的相关性分析

目的探讨人乳头瘤病毒(HPV)感染情况、阴道微环境指标与宫颈病变的相关性。方法选取2022年1月至2023年4月该院收治的307例宫颈病变患者作为研究对象,按照其液基细胞学检查(TCT)和病理检查结果分为低级别上皮内瘤变(LSIL)组(169例)、高级别上皮内瘤变(HSIL)组(97例)和宫颈癌组(SCC)(41例);另选取同期该院200例TCT结果正常无宫颈病变的健康体检者作为对照组。对所有研究对象进行HPV和阴道微环境检测。采用Spearman相关对宫颈病变严重程度与年龄的相关性进行分析。结果宫颈病变严重程度与年龄呈正相关关(r=0.306,P<0.05)。HPV感染率较高的型别依次为16、52、58、53型。LSIL组、HSIL组和SCC组HPV多重感染率均高于对照组,HSIL组和SCC组均高于LSIL组,差异均有统计学意义(P<0.05);SCC组HPV多重感染率与HSIL组比较,差异无统计学意义(P>0.05)。酸碱度(pH)、过氧化氢(H 2O 2)、白细胞酯酶(LE)异常比例均为SCC组>HSIL组>LSIL组>对照组,且SCC组、HSIL组和LSIL组与对照组比较,差异均有统计学意义(P<0.05)。阴道清洁度异常比例为SCC组>HSIL组>LSIL组>对照组,LSIL组阴道清洁度异常比例与对照组比较,差异无统计学意义(P>0.05),HSIL组和SCC组阴道清洁度异常比例与对照组比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,阴道pH>4.5、LE阳性、清洁度为Ⅲ°~Ⅳ°增加了宫颈病变发生的风险,H 2O 2阳性对宫颈病变的发生有抑制作用。结论HPV感染、阴道微环境指标异常改变与宫颈病变的发生和发展存在一定的相关性,可为临床预防和治疗宫颈病变提供参考依据。

CIN筛查方法的研究进展

子宫颈上皮内瘤变(CIN)是与子宫颈浸润癌密切相关的一组子宫颈病变,是临床最常见的威胁妇女健康的疾病之一,分为CIN1、CIN2、CIN3三级。大部分低级别鳞状上皮内病变(LSIL)即CIN1可自然消退,但高级别鳞状上皮内病变(HSIL)即部分CIN2、CIN3具有癌变的潜能。因此,早期通过筛查发现CIN并及时治疗高级别病变,对于预防妇女罹患宫颈癌尤为重要。本文将主要探讨目前提高CIN诊断率的筛查技术和检测方法,为临床工作中宫颈癌筛查技术的选择和筛查方案的制定提供参考依据。