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1.
Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2-7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio (PR) = 1.61, 95% confidence interval (CI): 1.4-1.8). High-risk HPV types (71 vs 40%, PR = 1.79, 95% CI: 1.5-2.2), in particular HPV-16+18 (22 vs 9%, PR = 2.35, 95% CI: 1.4-4.0), and multiple HPV infections (56 vs 23%, PR = 2.45, 95% CI: 1.8-3.3) were more prevalent in HIV-1-infected women. High-grade SIL (HSIL) was identified in 3.8% of the women. Human immunodeficiency virus type 1 infection was strongly associated with presence of HSIL (adjusted odds ratio = 17.0; 95% CI 2.2-134.1, P = 0.007) after controlling for high-risk HPV infection and other risk factors for HSIL. Nine of 14 (63%) HSIL cases were associated with HPV-16 or HPV-18 infection, and might have been prevented by an effective HPV-16/18 vaccine.  相似文献   

2.
Before guidelines can be set for the use of high-risk human papillomavirus (HR HPV) testing in cervical cancer screening and vaccine preparation, age-related prevalence of HR HPV types in cytologically normal smears has to be known. Therefore, in a cross-sectional study the prevalence of 37 different HPV genotypes and putatively unidentified HPV types was determined in 3,305 cytologically normal cervical smears from the general female population (15-69 years of age) using an HPV general primer GP5+/bioGP6+ mediated PCR assay. Subsequently, HPV-positive cervical smears were typed for 19 HR and 18 low-risk (LR) HPVs with an enzyme immunoassay using HPV type-specific oligoprobes in cocktails and individually, respectively. Overall, -HR and -LR HPV prevalences appeared to be of 4.6%, 3.3%, and 1.0%, respectively. Twenty-six different HPV types were detected in the 152 HPV-positive samples, the most prevalent types being HPV 16, 31, and 18. With regard to age, a peak prevalence of 19.6% for all HPVs was found in women 25-29 years of age, which declined to a mean of 4.3% in women over 30 years. With regard cytologically normal cervical smears (n = 3, 011) of women participating in the population-based screening program in the Netherlands (30 to 60 years), all HR HPVs showed decreased occurrence with increasing age, whereas the prevalence of LR HPV types remained constant. We suggest that screening for abnormal cytology implies screening for HR HPV infections and the subsequent treatment results in a decline of HR HPV prevalence in contrast to LR HPV prevalence during the years of screening.  相似文献   

3.
Adenocarcinoma in situ (AIS) is considered a precursor of adenocarcinoma. Cervical adenocarcinoma has been associated with human papillomavirus (HPV), while other subtypes of AIS and endocervical adenocarcinoma have no precursor lesions and are not associated with HPV. Cervical cytology and HPV genotyping are important in the detection of these different subtypes. Notably, endometrial lesions and infiltration with secondary adenocarcinoma may lead to misdiagnosis of endocervical lesions. The aim of the present study was to avoid misdiagnosis of squamous cell changes and endometrial lesions as endocervical lesions in cervical screening. A total of 210,510 female cytological samples were analyzed between the beginning of January 2020 and the beginning of January 2021. The samples were processed for conventional cytological techniques, and for molecular detection and subtyping of high-risk HPV (HPV-HR) according to the advice and measurements of BD Biosciences (117,765 samples) and the PapilloCheck® HPV test (5,579 samples). The present study was carried out in Germany using the Munich classification III. II-g (Bethesda classification: atypical glandular cells not otherwise specified) was detected in 0.12% of cases under the age of 35 years. Another peak was noticed within the 41–60-years age group (0.11%). In the 41–50-years age group, a peak for II-e (Bethesda classification: Endometrial cells) (1.5%) was identified. An association was revealed between HPV16, HPV18 and HPV45 with cervical intraepithelial neoplasia III, AIS, endocervical adenocarcinoma and squamous cell carcinoma, in addition to other HPV-HR subtypes, such as HPV33/58, as well as 52, 56/59/66 in the different age groups. In patients aged <35 years, 0.03% of cases were vaccinated cases against HPV. In the 35–40-years age group, there was only one vaccinated case (0.0045%); in the 41–50-years age group, there were 11 vaccinated cases (0.031%); and in the 51–60-years age group, there was one vaccinated case (0.002%). No patients aged >60 years were vaccinated against HPV in the analyzed cohort. In conclusion, most cases of HPV-associated glandular dysplastic changes and neoplasia occurred in sexually active women aged between 35 and 60 years. In addition, endocervical adenocarcinoma may occur at any age with or without an HPV infection.  相似文献   

4.
We evaluated the relationship between the dietary intake of vegetables and fruits, and the risk of cervical intraepithelial neoplasia (CIN) and determined whether these associations were modified by human papillomavirus (HPV) viral load. We enrolled 1,096 women aged 18–65 to participate in a HPV cohort study from March 2006 up to present. For this analysis, we included 328 HPV-positive women (166 controls, 90 CIN I and 72 CIN II/III). The multivariate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated by multinomial logistic methods. After controlling for potential confounders, we found that a higher HPV viral load was associated with an increased risk of CIN I (OR = 2.68, 95% CI, 1.19–6.04) and CIN II/III (OR = 2.78, 95% CI, 1.15–6.72). The relationships between HPV infection, dietary intake of vegetables and fruits and risk of CIN were not statistically significant. However, subjects with lower intake of vegetables and fruits, and a higher viral load (≥15.5) have a higher risk of CIN II/III (OR = 2.84(1.26–6.42), interaction p = 0.06 for vegetables; OR = 2.93(1.25–6.87), interaction p = 0.01 for fruits), compared with subjects with lower intake of vegetables and fruits, and a lower viral load (<15.5). Our findings suggest that the dietary intake of vegetables and fruits is associated with the progression of cervical carcinogenesis.  相似文献   

5.
An endoscopic survey was undertaken in Jiaoxian, People's Republic of China, a population at low risk for oesophageal cancer, to determine the prevalence of precancerous lesions of the oesophagus, and this rate was compared with the prevalence observed previously in high-risk populations in Iran and Linxian, China. The study involved 252 subjects whose exposure to suspected risk factors was determined by a questionnaire and all of whom underwent physical examination and oesophagoscopy, including cytology and biopsy. Chronic oesophagitis, with endoscopic and histologic characteristics similar to those observed in the high-risk populations of Iran and Linxian, was found in 28% of the study subjects compared to 80% in Iran and 65% in Linxian. Oesophagitis accompanied by atrophy of the epithelium was found in 0.4% compared to 10.5% in Iran and 10.8% in Linxian. No case of dysplasia was diagnosed in Jiaoxian while this condition was diagnosed in 4% of the subjects examined in Iran and in 8% of those in Linxian. The findings suggest that these lesions are in fact precancerous. Vitamin analysis showed that riboflavin deficiency was widespread in Jiaoxian, as in Iran and Linxian, but was more severe in Linxian than in Jiaoxian. No significant difference was found in the mean levels of retinol, beta-carotene and zinc between the two populations.  相似文献   

6.
7.
高危型人乳头瘤病毒对宫颈癌及癌前病变诊断价值的探讨   总被引:1,自引:1,他引:1  
为了探讨高危型人乳头瘤病毒(HPV)检测在宫颈癌及癌前病变中的诊断价值,采用第2代杂交捕获(HC-2)技术对325例妇科疾病患者[慢性宫颈炎56例,宫烦上皮内瘤变(CIN)Ⅰ41例,CIN Ⅱ 33例,CIN Ⅲ 91例,宫颈癌104例]进行HPV DNA阳性率和含量浏定.慢性宫颈炎、CIN Ⅰ级、CIN Ⅱ~Ⅲ级和宫颈癌患者HPV阳性感染率分别为35.7%,61.0%,91.0%和100.0%o;宫颈癌前病变(CIN I~Ⅲ)和宫颈癌的HPV DNA含量均明显高于慢性宫颈炎,差异有统计学意义,P<0. 05;宫颐癌的HPV DNA含量明显高于宫颈癌前病变(CINⅠ~Ⅲ),差异有统计学意义,P<0.05.初步研究结果提示,HPV DNA阳性感染率随宫颈病变程度的加重而升高;高危型HPV在慢性宫颈炎、CIN和宫颈癌中的病毒含量随宫颈病变程度的加重呈上升趋势.高危型HPV可以作为宫颈癌及癌前病变的重要检测指标.  相似文献   

8.
目的:分析高危型HPV感染在宫颈癌前病变、宫颈癌发生和发展中的关系,为宫颈病变的筛查和HPV疫苗的选择提供理论依据。方法:选择来我院妇科肿瘤中心就诊的1 197例患者作为研究对象,根据病理检查结果将病例分为慢性宫颈炎组(212例)、LSIL组(142例)、HSIL组(484例)和宫颈癌组(359例),检测各组高危型HPV感染的情况,分析不同组HPV的阳性率及HPV亚型的分布。结果:慢性宫颈炎组 HPV 感染阳性率为9.43%,LSIL组为78.87%,HSIL组为92.15%,宫颈癌组为97.77%,各组间阳性率两两比较差异有统计学意义(P<0.001)。各组中,高危HPV单一感染率均大于多重感染率,差异有统计学意义(P<0.001)。慢性宫颈炎组以HPV52、HPV16、HPV58为主要亚型(阳性率分别为 3.77%、2.83%和 1.41%),LSIL组以HPV52、HPV16、HPV58为主要亚型(阳性率分别为 23.94%、21.13%和 16.90%),HSIL组以HPV16、HPV52、HPV58为主要亚型(阳性率分别为33.06%、29.34%和 19.42%),宫颈癌组以HPV16、HPV58、HPV52为主要亚型(阳性率分别为 65.18%、20.89%和 10.86%)。本地区HSIL及宫颈癌人群感染率最高的5种亚型是HPV16、HPV18、HPV33、HPV52、HPV58。结论:宫颈病变程度越严重,HPV阳性率越高,不同程度宫颈病变HPV感染的亚型分布有差异。高危型HPV检测对本地区宫颈病变的早期筛查及HPV疫苗的接种有重要的指导意义。  相似文献   

9.
Women referred for colposcopy with mild and moderate dyskaryosis and found to have only minor cervical abnormalities were screened for oncogenic human papilloma virus (HPV) types. The natural development of these abnormalities in 42 HPV-positive women was assessed by cytology and colposcopy at 6-month intervals for up to 2 years. As is the case with cancers and high-grade cervical intra-epithelial neoplasia (CIN), minor cervical abnormalities were frequently found to be associated with HPV16, -18, -31 and -33. Viral persistence and the development of high-grade lesions were found to be closely associated with HPV16; 56% of HPV16 isolates were persistent compared to 7% of other HPV types, and all 4 subsequent CIN 3 lesions were in women with persistent infection. A striking association of persistence with a variant of HPV16 having a base change at nucleotide 350 was observed. Ten of 12 women with this variant had persistent infection compared to only 1 of 16 women infected with the HPV16 prototype. © 1996 Wiley-Liss, Inc.  相似文献   

10.
In mammography screening programmes, women are screened according to a one-size-fits-all principle. Tailored screening, based on risk levels, may lead to a better balance of benefits and harms. With microsimulation modelling, we determined optimal mammography screening strategies for women at lower (relative risk [RR] 0.75) and higher (RR 1.8) than average risk of breast cancer, eligible for screening, using the incremental cost-effectiveness ratio (ICER) of current uniform screening in the Netherlands (biennial [B] 50-74) as a threshold ICER. Strategies varied by interval (annual [A], biennial, triennial [T]) and age range. The number of life-years gained (LYG), breast cancer deaths averted, overdiagnosed cases, false-positive mammograms, ICERs and harm-benefit ratios were calculated. Optimal risk-based screening scenarios, below the threshold ICER of €8883/LYG, were T50-71 (€7840/LYG) for low-risk and B40-74 (€6062/LYG) for high-risk women. T50-71 screening in low-risk women resulted in a 33% reduction in false-positive findings, a similar reduction in costs and improved harm-benefit ratios compared to the current screening schedule. B40-74 in high-risk women led to an increase in screening benefit, compared to current B50-74 screening, but a relatively higher increase in false-positive findings. In conclusion, optimal screening consisted of a longer interval and lower stopping age than current uniform screening for low-risk women, and a lower starting age for high-risk women. Extending the interval for women at lower risk from biennial to triennial screening reduced harms and costs while maintaining most of the screening benefit.  相似文献   

11.
12.
Few natural history studies of cervical human papillomavirus (HPV) incidence and duration have been conducted among older women, especially from multiethnic populations. Viral and nonviral determinants of HPV acquisition and clearance were examined among 972 sexually active women, ages 18 to 85 years, recruited from clinics on Oahu, Hawaii, and followed for a mean duration of 15 months (range, 2-56 months). Interviews and cervical cell specimens for cytology and HPV DNA detection by PCR, using the PGMY09/PGMY11 primer system, were obtained at baseline and at 4-month intervals. The prevalence of cervical HPV infection was 25.6% at study entry. A total of 476 incident genotype-specific infections were observed during the follow-up period. The incidence of high-risk (HR) HPV types (9.26 per 1,000 woman-months) was similar to low-risk (LR) HPV types (8.24 per 1,000 woman-months). The most commonly acquired HR-HPV types were HPV-52, HPV-16, and HPV-31; and their incidence was increased significantly with a coexisting cervical HPV infection. Cervical HPV acquisition decreased with age, income, and long-term use of oral contraceptives and increased with number of sexual partners, use of hormonal creams, alcohol drinking, and condom use by a sexual partner. Cohort participants cleared 265 of the 476 incident infections during follow-up. LR-HPV infections cleared more rapidly than did HR-HPV infections (median, 180 days versus 224 days). Clearance times were enhanced among older women and women with multiple infections. Our data suggest several viral and nonviral determinants of cervical HPV acquisition and clearance that might be used in cervical cancer prevention programs.  相似文献   

13.
Introduction: High-risk human papillomavirus (hrHPV) testing is expected to replace cytology as primary screening method for cervical cancer screening in an increasing number of countries. The high sensitivity of hrHPV testing is combined with a limited specificity which makes triaging of hrHPV positive women necessary. As an ideal triage method does not yet exist, an optimal triage strategy for hrHPV positive women based on current knowledge should be obtained. The aim of this article is to present an overview of available options for triage of hrHPV positive women, with their strengths and limitations and possible future opportunities.

Areas covered: Current knowledge on morphological biomarkers, molecular biomarkers and combined triage strategies will be discussed to give an overview of the state-of-the-art on triaging hrHPV positive women. The literature search was limited to studies on triage strategies for hrHPV positive women.

Expert commentary: Experience with morphology-based biomarkers makes these a valuable triage method. However, they lack the ability of differentiating productive from transforming infections. Molecular biomarkers are objective, highly reproducible, can be used in high throughput testing, and show promising results. With more extensive knowledge on these molecular markers, cervical cancer screening may transform to a full molecular screening in the future.  相似文献   


14.
To determine whether the content of the matrix protein tenascin-C (Tn-C) is of diagnostic or prognostic value in cervical lesions, we evaluated increases in Tn-C immunoreactivity in 80 formalin-fixed, paraffin-embedded biopsies and surgical specimens of the uterine cervix. Tn-C content in the basement membrane zone and in the stroma was graded and compared to some prognostic parameters. In the normal cervix, Tn-C formed a thin continuous band. In cervicitis, Tn-C bands thickened in the basement membrane zone and the adjacent stroma in the form of thin filaments. In 30 squamous intraepithelial lesions (SILs) of various grades, Tn-C bands were either slightly (1+) or moderately (2+) thickened in the basement membrane zone, while slight stromal Tn-C immunoreactivity in the form of thin bands was observed in 12 cases, regardless of grade and inflammatory stromal reaction. In invasive carcinoma, Tn-C content was markedly increased in the stroma and around the invasive nests of tumors. The intensity of Tn-C immunoreactivity was significantly higher in grade I tumors than in others (p < 0.04). The intensity of increase in Tn-C immunoreactivity was 10.5-fold (95% CI 3.39-32.5) higher in invasive cervical carcinomas than in others (cervicitis, low-grade SIL and high-grade SIL) (p = 0.0001). A significant correlation was found between weak Tn-C immunoreactivity and lymphatic space invasion (p = 0.001), lymph node metastasis (p = 0.01), desmoplastic stromal component (p = 0.0001) and stromal inflammation (p = 0.002). In conclusion, increase in Tn-C immunoreactivity may be of value in the assessment of noninvasive and invasive cervical lesions and the appearance of Tn-C may be an indicator of adequate biologic defense in cervical cancer patients.  相似文献   

15.

Objective

Presence of high-risk factor in cervical cancer is known to be associated with decreased survival outcomes. However, the significance of multiple high-risk factors in early-stage cervical cancer related to survival outcomes, recurrence patterns, and treatment implications is not well elucidated.

Methods

A retrospective study was conducted for surgically treated cervical cancer patients (stage IA2-IIB, n=540). Surgical-pathological risk factors were examined and tumors expressing ≥1 high-risk factors (nodal metastasis, parametrial involvement, or positive surgical margin) were eligible for analysis (n=177, 32.8%). Survival analysis was performed based on the number of high-risk factors and the type of adjuvant therapy.

Results

There were 68 cases (38.4%) expressed multiple high-risk factors (2 high-risk factors: n=58, 32.8%; 3 high-risk factors: n=10, 5.6%). Multiple high-risk factors remained an independent prognosticator for decreased survival outcomes after controlling for age, histology, stage, and treatment type (disease-free survival: hazard ratio [HR], 2.34; p=0.002; overall survival: HR, 2.32; p=0.007). Postoperatively, 101 cases (57.1%) received concurrent chemoradiotherapy (CCRT) and 76 cases (42.9%) received radiotherapy (RT) alone. CCRT was beneficial in single high-risk factor cases: HRs for CCRT over RT alone for cumulative risk of locoregional and distant recurrence, 0.27 (p=0.022) and 0.27 (p=0.005), respectively. However, tumor expressing multiple high-risk factors completely offset the benefit of CCRT over RT alone for the risk of distant recurrence: HR for locoregional and distant recurrence, 0.31 (p=0.071) and 0.99 (p=0.980), respectively.

Conclusion

Special consideration for the significance of multiple high-risk factors merits further investigation in the management of surgically treated early-stage cervical cancer.  相似文献   

16.
We compared cytology with Hybrid Capture 2 (HC2), cobas, CLART and APTIMA Human Papillomavirus (HPV) assays in primary cervical screening at age 23–29 years based on data from the Danish Horizon study. SurePath samples were collected from 1278 women undergoing routine cytology-based screening. Abnormal cytology was managed according to the routine recommendations, and women with cytology-normal/HPV-positive samples were invited for repeated cytology and HPV testing in 1.5 years. Loss to follow-up was similar between HPV assays. ⩾CIN3 was detected in 44 women. The sensitivity of HC2 for ⩾CIN3 was 95% (95% confidence interval (CI): 85–99), of cobas 98% (95% CI: 88–100), of CLART 100% (95% CI: 92–100), of APTIMA 82% (95% CI: 67–92), and of cytology 59% (95% CI: 43–74). Specificity for ⩾CIN3 varied between 61% (95% CI: 59–64) for cobas and 75% (95% CI: 73–78) for APTIMA, and was 94% (95% CI: 93–96) for cytology. Similar results were observed for ⩾CIN2 (N = 68). HPV screening with cytological triage doubled the number of colposcopies compared to cytology screening, and increased the frequency of repeated testing by four (APTIMA) to seven (cobas) times. The positive predictive value of a referral for colposcopy was relatively high for all screening tests (⩾30% for ⩾CIN3, and ⩾50% for ⩾CIN2). CIN1 was detected by cytology in ∼1% of women, and in ∼2% by any of the four HPV assays. Although highly sensitive, HPV-based screening of young Danish women should be approached cautiously, as it resulted in large reductions in specificity, and increased the demand for additional testing.  相似文献   

17.
Given the lower specificity for high-grade cervical lesions of high-risk human papillomavirus (hrHPV) testing compared to cytology, additional triage testing for hrHPV test-positive women is needed to detect high-grade cervical lesions. Here, we tested whether combined methylation analysis for cell adhesion molecule 1 (CADM1) and T-lymphocyte maturation associated protein (MAL), both functionally involved in cervical carcinogenesis, could serve as such a triage marker. Four quantitative methylation-specific PCRs (qMSP), two for CADM1 (regions M12 and M18) and MAL (regions M1 and M2) each, were applied to 261 cervical tissue specimens ranging from no neoplasia to carcinoma. When qMSPs were combined and positivity for at least one of the qMSPs in the combination was taken into account, the highest positivity rates for cervical intraepithelial neoplasia grade 3 (CIN3) lesions (97%) and squamous cell- and adeno-carcinomas (99%) were obtained by combining a single CADM1 marker with a single MAL marker. Subsequent qMSP analysis of 70 GP5+/6+-PCR hrHPV-positive scrapings revealed that a two-marker panel consisting of CADM1-M18 and MAL-M1 was most discriminative, detecting 90% of women with CIN3 (n = 30), whereas it showed a positive result in only 13.5% of women without cervical disease (n = 40). Finally, we applied hrHPV GP5+/6+-PCR testing followed by CADM1-M18/MAL-M1 methylation analysis to a cohort of 79 women visiting the outpatient colposcopy clinic. hrHPV testing revealed a sensitivity of 97% and a specificity of 33% for CIN3+. Additional CADM1-M18/MAL-M1 methylation analysis on the hrHPV-positive women increased the specificity to 78% with a sensitivity of 70%. In conclusion, the methylation marker panel CADM1-M18 and MAL-M1 may serve as an alternative molecular triage tool for hrHPV-positive women.  相似文献   

18.
19.
Paraffin embedded material of multiple primary cancers and other hyperplastic tumours from fifteen patients were analyzed by PCR and in situ hybridization for the presence of HPV DNA in the lesions. All patients had also high grade cervical intraepithelial dysplasia (CIN III) and breast carcinomas and were selected from a previous study enrolling 46 women with CIN III and breast carcinomas. HPV 16 was detected by PCR in 8/15 patients (53%), with eleven HPV 16 positive tumours. HPV 16 was detected in two malignant melanomas, one basal cell carcinoma, one squamous cell carcinoma of the vulva, one Bowen disease of the vulva, two high grade vaginal intraepithelial neoplasias, one cancer corporis uteri, one bronchial carcinoma and two lymphomas. Three cases, two high grade vaginal intraepithelial neoplasia and a squamous cell carcinoma of the vulva, were also reported to be positive by in situ hybridization. 5/8 patients (63%) with HPV 16 positive second cancers had also HPV 16 positive breast carcinomas. All fifteen patients with second cancers after CIN III had HPV 16 positive CIN III lesions; 53% of the patients had also a familial cancer history. We assume that HPV 16 may be involved in the development of different second cancers in women with HPV 16 positive CIN III.  相似文献   

20.
目的 了解汉族、维吾尔族宫颈癌及宫颈病变患者人乳头状瘤病毒(HPV)的感染及其基因型分布情况,并分析两族间的差异。方法 采用导流杂交基因芯片技术检测2011年11月至2012年5月在新疆维吾尔自治区人民医院住院或门诊就诊的244例宫颈癌及宫颈病变患者(汉族、维吾尔族各122例)的HPV基因型及分布。结果 244例患者中共检测出18种HPV亚型,其中HPV16型在汉族和维吾尔族中所占的比例均最高;在慢性宫颈炎和宫颈上皮内瘤变(CIN)中检测出18种HPV亚型,宫颈癌中检测出8种。随病变程度的加重,HPV亚型趋于集中,两族中趋于集中的HPV亚型为HPV16、18、52、58、53、39型,其检出率在两族患者间差异无统计学意义(P>0.05);汉族和维吾尔族HPV多重感染率分别为22.13%(27/122)和34.43%(42/122),差异有统计学意义(P<0.05)。结论 汉族和维吾尔族妇女宫颈癌及宫颈病变中HPV型别分布存在一定差异,维吾尔族HPV多重感染率高于汉族妇女,这可能是新疆维吾尔族妇女宫颈癌发生率显著高于汉族妇女的原因之一。  相似文献   

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