Clinical significance of hWAPL polymorphisms in the risk of cervical carcinogenesis

To investigate the clinical significance of human wings apart-like (hWAPL) genetic polymorphisms in cervical carcinogenesis. hWAPL polymorphisms and human papillomavirus (HPV) types were examined in 175 cervical smears of exfoliated cervical cell samples using a real-time polymerase chain reaction system. A significant difference was detected in the frequency of the CC genotype between the HPV(+) low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) groups [Odds ratio 0.21, 95% confidence interval (CI) 0.0723–0.61; P = 0.0029]. A significant difference was noted in the frequency of the CC genotype between the high-risk HPV-positive LSIL and HSIL groups (odds ratio 0.2955, 95% CI 0.0893–0.9771; P = 0.0414). The CC genotype of hWAPL gene promoter polymorphism may be associated with cervical carcinogenesis.     

靖江地区宫颈病变患者高危型人乳头瘤病毒感染及其基因型分析

目的：研究靖江地区各组宫颈病变中高危型人乳头瘤病毒（HPV）感染率及其基因型分布。方法：采用实时荧光PCR检测方法检测334例宫颈脱落细胞标本中高危型HPV及其基因型。结果：高危型HPV在宫颈炎组、湿疣组、低度鳞状上皮细胞内病变（LSIL）组、高度鳞状上皮细胞内病变（HSIL）组中的感染率分别为24.2%、58.2%、49.3%、69.5%;HPV 16、18、33、58型在宫颈病变中是最常见的HPV型别,其中,HPV16型在宫颈炎组、湿疣组、LSIL组、HSIL组中所占比例逐渐增高,分别为17.9%、18.9%、30.8%、41.9%。结论：高危型HPV感染率随着宫颈病变程度的加重而升高,HPV16型是高危型HPV感染中的主要亚型,HPV18、33、52、58也较常见,其余型别很少。     

靖江地区宫颈病变患者高危型人乳头瘤病毒感染及其基因型分析

目的:研究靖江地区各组宫颈病变中高危型人乳头瘤病毒(HPV)感染率及其基因型分布。方法:采用实时荧光PCR检测方法检测334例宫颈脱落细胞标本中高危型HPV及其基因型。结果:高危型HPV在宫颈炎组、湿疣组、低度鳞状上皮细胞内病变(LSIL)组、高度鳞状上皮细胞内病变(HSIL)组中的感染率分别为24.2%、58.2%、49.3%、69.5%;HPV 16、18、33、58型在宫颈病变中是最常见的HPV型别,其中,HPV16型在宫颈炎组、湿疣组、LSIL组、HSIL组中所占比例逐渐增高,分别为17.9%、18.9%、30.8%、41.9%。结论:高危型HPV感染率随着宫颈病变程度的加重而升高,HPV16型是高危型HPV感染中的主要亚型,HPV18、33、52、58也较常见,其余型别很少。     

Germline polymorphisms of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 in cervical carcinogenesis

The clinical significance of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in cervical carcinogenesis was investigated. Germline polymorphisms of GSTM1, GSTT1 and p53 codon 72 together with human papillomavirus (HPV) types were examined in a total of 457 blood and cervical smear samples from normal healthy women and the patients with premalignant and malignant cervical lesions. The 167 patients with low-grade squamous intraepithelial lesion (LSIL), 49 with high-grade SIL (HSIL) and 83 with squamous cell carcinoma (SCC) had significantly higher frequency of high-risk HPV than 158 controls. The 49 patients with HSIL and 83 with SCC had statistically higher frequency of null GSTT1 genotype than 158 controls. There was an increased odds ratio for null GSTT1 genotype in HSIL and SCC cases compared with controls among 191 patients with high-risk HPV. The 67 cases with HPV types 16 and/or 18 had higher frequency of the GSTT1 null genotype than 186 with other types of HPV. There was no statistical difference in the polymorphic frequency of GSTM1 and p53 codon 72 genotypes between SILs and controls with or without high-risk HPV. These results suggest that GSTT1 null genotype may increase the risk of cervical cancer particularly in the cases with high-risk HPV types in a Japanese population.     

Human papillomavirus genotypes among infected Thai women with different cytological findings by analysis of E1 genes

Cervical cytological data may not be sufficient for cervical cancer screening and prevention. In this project, we determined HPV genotype among infected Thai women with different cytological findings by characterization of E1 genes. Five hundred and thirty-five specimens were tested by PCR amplification of the E1 genes. HPV genotypes were determined by sequencing, comparison with the GenBank database and were analyzed in relation to different cytological findings. HPV-DNA by PCR were typed and revealed 32 different genotypes. HR-HPV (HPV16, 18 or 52) was detected in all samples with cervical cancer cytology. HPV16 was most prevalent irrespective of cervical cytology. Moreover, HPV31 and 52 were most prevalent in the HSIL and LSIL groups whereas HPV66 was found mostly in the LSIL group. The LSIL group displayed the highest variation of HPV genotypes. Moreover, HPV31 and 52 predominated in the HSIL and LSIL groups especially HPV52 which was found in cancer samples. We hoped that these data of HPV genotypes can be used as preliminary data of HPV in Thailand and can serve as basic data for future research into the HPV genotype in south-east Asia.     

Prevalence of human papillomavirus infection and genotype distribution determined by the cyclic-catcher melting temperature analysis in Korean medical checkup population

Although cytology screening has reduced the incidence and mortality rate of cervical cancer significantly, its usefulness is limited to samples from the site of the lesion, resulting in its low sensitivity and unsuitability for use in medical checkups. The purpose of the present study was to evaluate the prevalence of HPV infection using genotype distribution and to analyze the correlation of the HPV DNA test results with cytological results. We also evaluated the benefits of quantitative information obtained from cyclic-catcher melting temperature analysis (CMTA) in screening for cervical cancer. We performed cyclic-CMTA using Anyplex? II HPV28 Detection in combination with cervical cytology for 2,181 subjects. The following HPV positivity types were detected using cyclic-CMTA and HPV positivity was found to increase together with the severity of the cytology results: (1) For 419 HPV positive specimens, HPV DNA was detected in 18.1% of normal specimens, 78.3% of ASCUS, and all of LSIL and HSIL; (2) high-risk HPV DNAs were detected in 63.3% of normal (N=547), 65.9% of ASCUS (N=41), 76.9% of LSIL (N=13), and 88.9% of HSIL (N=9) among total detected HPV DNA regardless multiple detection; (3) multiple HPV genotypes were detected in 4.8% of normal specimens (N=2,146), 52.2% of ASCUS (N=23), 57.1% of LSIL (N=7), and 40.0% of HSIL (N=5). In addition, a high level of viral DNA was observed using cyclic-CMTA in all specimens beyond the LSIL stage according to cytology, while only 6% of specimens with normal cytology showed a correlation with viral quantitation by cyclic-CMTA. The combination of HPV genotyping with a quantitative assay and cytology will allow for a more accurate diagnosis of cervical cancer.     

Cervical squamous intraepithelial lesions and associated cervical infections in an HIV‐positive population in Rural Mpumalanga,South Africa

P. J. Swanepoel, P. Michelow, R. Du Plessis, I. G. Proudfoot, G. A. Tarr, S. L. Bockel, C. J. Swanepoel
Cervical squamous intraepithelial lesions and associated cervical infections in an HIV‐positive population in Rural Mpumalanga, South Africa Background: The incidences of genital human papillomavirus (HPV) infection, associated squamous intraepithelial lesions and cervical squamous cell carcinoma are significantly increased in HIV‐positive women. The role of other cervicovaginal infections in the acquisition of the HPV infection, cervical carcinogenesis and genital HIV infection remains largely speculative. Methods: A retrospective study was conducted including 1087 HIV‐positive women in rural Mpumalanga province, South Africa, for the period 1 May 2009 to 31 August 2010. For each patient, the age at first presentation, cervical cytological diagnosis, subsequent follow‐up cytology and histology, and microscopically visible infections (including endemic Bilharzia) were tabulated and statistically analysed. Results: The prevalence of low‐grade squamous intraepithelial lesion (LSIL), high‐grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, atypical squamous cells of undetermined significance (ASC‐US) and atypical squamous cells, cannot exclude HSIL (ASC‐H) in the study population were 22.1%, 30.9%, 0.6%, 13.5% and 4.0%, respectively. LSIL, HSIL and squamous cell carcinoma were diagnosed, respectively, at the average ages of 35.7, 37.9 and 37.2 years. Four patients with cervical intraepithelial neoplasia grade 1 (CIN1), 32 with CIN2/CIN3 and two with cervical squamous cell carcinoma were also diagnosed with Bilharzia. Of the other infections only bacterial vaginosis had a positive statistical correlation with HPV‐induced cervical abnormalities (LSIL, HSIL or squamous cell carcinoma). Conclusion: This study confirms the high prevalence of progressive HPV‐associated cervical disease in a rural Southern African HIV‐positive population, which is at least equal to or worse than in other African HIV‐positive studies. The high incidence of Bilharzia infection in those cases that underwent cervical cone excision suggests a possible relationship with progressive HPV disease and cervical carcinogenesis. Bacterial vaginosis (perhaps in combination with Bilharzia) may compromise the normal barriers against HPV and HIV infection.     

The 46359CT polymorphism of DNMT3B is associated with the risk of cervical cancer

Abnormal methylation is related to cancer development. Since DNMT3B is an enzyme that modulates genomic methylation, we hypothesized that genetic variants of the promoter DNMT3B may be associated with an increased risk of developing cervical cancer. Our aim was to investigate the association between ?579GT and 46359CT polymorphisms of DNMT3B and cervical cancer, high-grade squamous intraepithelial lesions (HSIL), and low-grade squamous intraepithelial lesions (LSIL). Samples from 200 healthy women and 130 women with squamous intraepithelial lesions (70 with cervical cancer, 30 with HSIL, and 30 with LSIL) were analyzed. Polymorphism genotyping was performed using PCR and restriction fragment length polymorphism. The ?579GT polymorphism was not associated with cervical cancer, HSIL, or LSIL. The CT genotype of 46359CT polymorphism was significantly associated with cervical cancer risk (OR 8.75, CI 1.27–374.1), whereas the TT genotype was associated with a significantly decreased risk of HSIL (OR 0.66, CI 0.01–0.32) and LSIL (OR 0.11, CI 0.026–0.45). Our results suggest that genotyping the 46359CT polymorphism in DNMT3B may help identify women who are genetically susceptible to cervical cancer development. Additional studies with larger sample sizes are necessary to confirm our findings.     

Diagnostic and prognostic significance of image cytometric DNA ploidy measurement in cytological samples of cervical squamous intraepithelial lesions

D. Demirel, N. Akyürek and I. Ramzy
Diagnostic and prognostic significance of image cytometric DNA ploidy measurement in cytological samples of cervical squamous intraepithelial lesions Objective: To study the DNA ploidy pattern of uterine cervical squamous intraepithelial lesions (SILs) and its diagnostic and prognostic significance. Methods: The study included 31 cases of SIL: 11 low‐grade (LSIL) and 20 high‐grade (HSIL). Feulgen–pararosaniline staining was performed on previously Papanicolaou‐stained smears and a DNA image cytometric study was performed. An internal reference was used to calibrate the samples. Results: All 31 cases of SIL, either LSIL or HSIL, were non‐diploid. Of the 11 cases of LSIL, four were tetraploid and seven were aneuploid, whereas, of the 20 cases of HSIL, four were tetraploid and 16 were aneuploid. Stemline aneuploidy was not a significant discriminator between LSIL and HSIL (P = 0.32). Based on single‐cell analysis, HSIL cases had significantly higher DNA content than LSIL cases (P < 0.01). When a mean of 30% or more was used for the 6c‐exceeding event (6cEE) value, the sensitivity and specificity to indicate HSIL were 83% and 64%, respectively, with a positive predictive value (PPV) of 81% and negative predictive value (NPV) of 65%. All HSIL cases were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on biopsy. In addition, cases which showed recurrence had more DNA content by single‐cell analysis than those with an indolent clinical behaviour: P = 0.04 and P = 0.03 for LSIL and HSIL, respectively. Conclusions: Image cytometric DNA analysis is a useful technique for diagnostic and prognostic purposes in uterine cervical SIL when appropriate ‘c’ values are used in single‐cell analysis. We propose that a >6c DNA content of 30% is useful as a cut‐off level for predicting cases with CIN2+ in DNA image cytometry of cervical smears.     

应用分子生物学方法检测宫颈液基细胞残液中HPV16／18感染的对比研究

对比免疫蛋白印迹及斑点杂交检测人乳头瘤病毒HPV16/18的检出率,以期找到子宫颈癌早期筛查的最佳方法。采用免疫蛋白印迹与斑点杂交分别对173份宫颈液基细胞进行HPV16/18检测。150例经宫颈液基细胞学镜下筛查为宫颈上皮内病变及宫颈癌的患者,其中免疫蛋白印迹对低度病变检出率为47.6%(30/63),对高度病变检出率为57.9%(33/57),对浸润癌的检出率为86.7%(26/30),其中鳞癌为85%(17/20),腺癌为90%(9/10),采用斑点杂交对低度病变检出率为28.6%(18/63),对高度病变检出率为42.1%(24/57),浸润癌的检出率为80%(24/30),其中鳞癌为75%(15/20),腺癌为90%(9/10)。采用免疫蛋白印迹对23例正常对照的细胞HPV检出率为13.1%(3/23),斑点杂交的检出率为8.7%(2/23)。各级宫颈病变中HPV16/18的检出率均较对照组差异有统计学意义(P<0.05)。免疫蛋白印迹检测HPV16/18比斑点杂交的检出率要高,为发现HPV一过性携带者,达到早期诊断的目的。     

Prevalence of human papillomavirus among Croatian women attending regular gynecological visit

Human papillomavirus (HPV) infection has been identified as major risk factor for cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. About 40 HPV viral types are commonly found in the genital tract. Most HPV infections resolve spontaneously, while persistent infection with oncogenic types, namely HPV 16 and 18 is necessary for CIN to occur and progress to cancer. Cervical screening is presently based on the Pap smear that is designed to diagnose precancerous lesions and cervical cancer The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among 361 women attending regular gynecological visit. There were 205 women (29+/-8 years old) without determined abnormal cervical lesions and 156 women (34+/-15 years old) with abnormal Pap smear; low grade squamous intraepitehelial lesions (LSIL, n=69), high grade squamous intraepithelial lesions (HSIL, n=72) and atypical squamous cells of undetermined significance (ASCUS, n=15). HPV DNA detection and genotyping was performed by Hybrid Capture 2 assay and additionally by consensus and type-specific primers directed PCR. The overall prevalence of high-risk HPV (hrHPV) in women with abnormal Pap smears was 67.9% (106/156), of which in ASCUS 33.4% (5/15), LSIL 62.3% (43/69) and HSIL 80.6% (58/72). In HPV positive specimens, HPV 16 was found as predominant type in 60.4% cases, followed by HPV 31 (8.5%), HPV 33 (6.6%) and HPV 18 (3.7%). In the group of women without obvious cervical changes the overall hrHPV prevalence was 35.6% with HPV 16 found in 43.8% cases, followed by HPV 31 (17.8%), HPV33 (9.5%) and HPV18 (6.8%). In both study groups, women with and without cervical lesions, the prevalence of HPVof indeterminate type was 14.2% and 13.7%, respectively. Our results indicate that cervical intraepithelial lesions are largely associated with HPV type 16, followed by HPV types 31, 33, 18 and HPV of indeterminate type. Although there is a significant difference in hrHPV DNA prevalence among two groups, no significant differences between particular hrHPV types distribution were observed.     

IFN-gamma and IL-12B polymorphisms in women with cervical intraepithellial neoplasia caused by human papillomavirus

The Human Papillomavirus (HPV) is a sexually transmitted organism associated with Cervical Intraepithelial Neoplasia (CIN) and cervical cancer, the second main cause of malignancy in women worldwide. The virus itself, however, is not enough to cause lesions on the cervix. Several studies suggest that some polymorphic sites changes the cytokines levels and influence the cancer development in HPV infected patients. In this study, we evaluated the presence of functional polymorphisms at +874 (T/A) IFNG and +1188 (A/C) IL-12B genes in cervical smears samples from 76 healthy women and 162 women, HPV positive, with CIN lesion--CIN I (45), CIN II (55), CIN III (53) and cervical cancer (9)--in Brazilian population. There was no significant differences in genotype (p = 0.4192) and allele (p = 0.370; OR = 1.20) distributions between CIN patients and control groups on IFNG allelic polymorphism. Moreover, for IL-12B gene, there was a significant difference in genotype (p = 0.015) and allele distribution (p = 0.014; OR = 0.5754) between the groups. When samples were stratified according to grade of cervical lesion, the AA genotype and A allele were less frequent in the group with low-grade cervical lesions than in group with high-grade cervical lesions (p = 0.0036 and p = 0.0010; OR = 0.3819, respectively), suggesting that the C allele (mutant) may protect against the emergence of CIN lesions and its progression.     

Cervical scrapes levels of insulin-like growth factor-II and insulin-like growth factor binding protein 3 in women with squamous intraepithelial lesions and cervical cancer

A growing number of studies have demonstrated an association between serum levels of insulin-like growth factors (IGFs) and IGF binding protein-3 (IGFBP-3) and increased risk for various cancers. The aim of this study was to evaluate the relationship between levels of IGF-II or IGFBP-3 in cervical scrapes with cervical cancer and precancerous lesions: low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). 4 groups of cases were examined: LSIL (n=20), HSIL (n=28), cervical cancer (n=45), and controls (n=51). Control subjects were women with normal, HPV DNA-negative Papanicolau (Pap) test. IGF-II and IGFBP-3 levels in cervical scrapes were measured by ELISA. Results show that median protein levels of IGF-II were significantly lower in cervical cancer cases vs. controls (446.5 ng/mg vs. 1,168.6 ng/mg, p<0.001). Significantly higher values of IGFBP-3 were found in HSIL vs. controls (median: 549.5 ng/mg vs. 216 ng/mg; p=0.018), and were not affected by HR HPV infection, meanwhile no significant differences were observed in IGFBP-3 levels between LSIL or cervical cancer as compared to controls. These data suggests that the progression to cervical cancer is associated with alterations in the IGF system and not affected by HR HPV infection. More studies are needed to understand the possible role of IGFBP-3 in cervical carcinogenesis.     

Glandular and squamous atypia and intraepithelial lesions in atrophic cervicovaginal smears. One institution's experience

OBJECTIVE: To review the cytologic features and follow-up histologic findings in atrophic cervicovaginal smears with the diagnoses of glandular or squamous atypia or intraepithelial lesion. STUDY DESIGN: A total of 228 cases were included in the study. The selection criteria included: age > 48 years and a diagnosis of either atypical glandular cells (AGC) (51 cases), cellular changes suggestive of human papillomavirus (HPV) infection (S/O HPV, 97 cases), low grade squamous intraepithelial lesion (LSIL) (60 cases) or high grade squamous intraepithelial lesion (HSIL) (20 cases). Follow-up biopsy information was available for 103 cases (45%). RESULTS: From the AGC group, 35 (69%) cases had tissue studies; 14 (40%) cases showed glandular lesions; 5 (14%) showed squamous intraepithelial lesion (SIL) and atypical cells. Follow-up information was available for 32 (33%) cases classified as S/O HPV; significant lesions (glandular/squamous) were found in 11 (34%). In the LSIL category, 22 (37%) cases had follow-up; 16 (73%) showed SIL. In the HSIL category, 14 cases (70%) underwent biopsy, and all showed SIL (four LSIL and nine HSIL) or squamous cell carcinoma. CONCLUSION: Even though atrophy-related epithelial changes often pose diagnostic difficulties in the interpretation of postmenopausal smears, application of reproducible and established cytologic criteria in diagnosing SIL and/or glandular lesions can improve diagnostic accuracy and result in selection of patients for follow-up tissue studies.     

Retrospective study of the prevalence of high-risk human papillomaviruses among Croatian women

The infection with Human papillomavirus (HPV) is the necessary cause for cervical cancer. There are at least 15 High-Risk (HR) HPV types that are significantly associated with progression of cervical intraepithelial neoplasia to cervical cancer. Since previous studies showed that the prevalence of HPV in cervical cancers varies among different geographic regions, we wanted to investigate the prevalence of HPV types in Croatia, especially low abundant HR HPV types. By means of consensus primers directed polymerase chain reaction (PCR), we analysed cervical DNA samples of 2,136 Croatian women, mostly with abnormal cervical smears, in order to detect the presence of HPV Type-specific primers were then used to determine Low-Risk (LR) HPV types 6/11 and HR HPV types 16, 18, 31, 33, 45, 52 and 58. Out of 2,136 specimens, 1,255 (58.8%) were positive for HPV More than half of positive samples were typed (64.5%) and 35.5% still remained untyped. Multiple HPV infections were found in 10.3% of the cases. The most prevalent type, including both single and multiple infections, was HPV16 with the prevalence of 15.9%, followed by HPV types 31, 6/11, 33, 18, 52, 45 and 58 with 8.7%, 7.1%, 4.5%, 3.8%, 2.3%, 1.2% and 1.1%, respectively. The significant increase of frequency from Low-grade Squamous Intraepithelial Lesions (LSIL) to High-grade Squamous Intraepithelial Lesions (HSIL) was observed for HR HPV types 16, 18, 31 and 33 but not 45, 52 and 58. The frequency of unknown HPV types was almost the same in cervical specimens of women with LSIL and those with HSIL, 19.8% and 21.1%, respectively. The prevalence of HPV infection rate decreased significantly with patient age from 68.5% (age group 12 to 24 years) to 38.8% (age group 45 to 54 years). But, in women aged 55 or older the overall prevalence increased to 56.6%. Our results indicate that prevalence of HR HPV types in Croatia is similar to other countries. We suggest that HPV positive women in Croatia should be closely monitored by typing for HR HPV types: 16, 18, 31, 33, 45, 52 and 58.     

Effectiveness of liquid-based cytology and papanicolaou tests in a low risk population

OBJECTIVE: To compare sensitivity an effectiveness of ThinPrep vs. Pap Test and determine whether the Hybrid Capture System II (HCII) for detection of human papillomavirus (HPV) could increase the sensitivity and effectiveness of cervical screening in a low risk population. STUDY DESIGN: We present a comparative observer, blind, "split sample" study of ThinPrep and Papanicolaou staining in a population of 2026 consecutive women. RESULTS: Conventional Papanicolaou stain detected lesions in 62 cases (3.06%), including 1 atypical glandular cell of undetermined significance (AGUS), 34 atypical squamous cells of undetermined significance (ASCUS) (1.73% of atypias), 20 (0.99%) low grade squamous intraepithelial lesions (LSIL), and 7 (0.35%) high grade squamous intraepithelial lesions (HSIL). ThinPrep detected lesions in 63 cases (3.11%), including 26 (1.28%) ASCUS, 27 (1.33%) LSIL and 10 (0.49%) HSIL. Despite this overall similarity, only 35 had a coincident cytopathologic result by both methods. The kappa concordance index between ThinPrep and Pap was 0.546. Sensitivity and specificity were 74.6 and 45.0 in ThinPrep and 69.5 and 25.0 in Papanicolaou-stained smears. High risk HPV (HR-HP 17) was positive in 13 of ZOASCUS and in 21 of 22 SIL. CONCLUSION: Technologies now widely available such as Thin Prep and viral detection aim to improve accuracy of screening.     

HPV-DNA 和TCT 检测在宫颈癌前病变筛查中的诊断价值

目的:探讨乳头瘤病毒定性检测( HPV- DNA)与液基薄层细胞学检查技术(TCT)在宫颈癌前病变中的诊断价值.方法:分别采用HPV- DNA及TCT法检测1536例患者,对TCT阳性、HPV- DNA阳性病例者进行阴道镜下活检.结果:随着病理诊断级别的升高,高危型HPV感染率上升,而低危型HPV感染多见于轻度不典型增生(CINⅠ)及其以下病变,HPV混合感染在各组间未见明显趋势.HPV-DNA检测与宫颈活检的符合率为66.78％.随着病理级别的升高,不典型鳞状细胞(ASCUS)组的感染率呈降低趋势,鳞状上皮内低度病变(LSIL)组感染率亦呈下降趋势,而鳞状上皮内高度病变(HSIL)组和鳞癌(SCC)组感染率均呈上升趋势,TCT检测与组织学诊断的符合率为66.67％,与HPV-DNA检查比较,差异无统计学意义(x=0.001,P＞0.05).结论:HPV-DNA、TCT及宫颈活检三者检测相结合,能明显提高诊断的正确性.     

Immunocytochemical detection of HPV high-risk type L1 capsid proteins in LSIL and HSIL as compared with detection of HPV L1 DNA

OBJECTIVE: To investigate the prevalence of HPV L1 capsid proteins in HPV-infected HSIL and LSIL. STUDY DESIGN: Cervical smears from 74 women with cytologically and histologically confirmed LSIL (n = 32) and HSIL (n = 42) were collected prospectively to detect HPV high-risk (hr) types 16, 18, 33, 35, 39, 45, 56 and 58 L1-DNA by standardized L1-consensus primer PCR (MY 09/11) and L1 capsid proteins by immunocytochemistry using monoclonal antibodies T31 (HPV16) and T16 (HPV hr) in a standardized protocol. RESULTS: In HSIL and LSIL, L1 DNA was found for HPV hr in 93% and 59% and for HPV16 in 69% and 37% of the specimens, respectively. HPV L1 capsid proteins were detected in HSIL and LSIL for HPV hr in 33% and 44% and for HPV16 in 29% and 31% of the specimens, respectively. Expression of L1 capsid proteins was significantly reduced, by 59.6% for HPV hr L1 DNA-positive HSIL (P < .01) and by 40.4% for HPV 16 L1 DNA-positive HSIL (P < .01). In HPV 16 DNA-positive and HPV hr DNA-positive LSIL, no significant reduction of corresponding L1 capsid protein expression could be demonstrated. CONCLUSION: These data suggest a disturbed viral cellular interaction in HPV 16 and HPV hr-infected HSIL, with loss of viral L1 capsid antigen. In this context there is a possible role of T31 and T16 as prognostic markers to predict the prognosis of CIN.     

Cervicovaginal smear abnormalities in sexually active adolescents. Implications for management

OBJECTIVE: To assess the prevalence and spectrum of Pap smear (PS) abnormalities in sexually active adolescents in comparison to adult women in order to determine whether management of adolescents should differ from that of adults. STUDY DESIGN: Five hundred twenty-four adolescents who had an initial PS at our institution from January to September 1997 were followed for 36 months with repeat PS and/or cervical biopsy. Initial PS results were compared with those of adult women. The chi 2 test was used to calculate the statistical significance of differences between the two groups. The qualified atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis in adolescents was correlated with follow-up data. RESULTS: The overall prevalence of squamous intraepithelial lesions (SILs) in adolescents was 29% as compared to 23% in adults. Almost all initial squamous lesions were ASCUS and low grade squamous intraepithelial lesion (LSIL); only one case of high grade squamous intraepithelial lesion (HSIL) was detected. On follow-up 18% and 2.4% of adolescents developed LSIL and HSIL, with a LSIL/HSIL ratio of 8/1 as compared to 5/1 in adults. The average time from initial PS to detection of HSIL was 20 months. All patients with HSIL except one had had one or more previous abnormal PSs. The positive predictive values (PPVs) for subsequent dysplasia for ASCUS favor reactive (ASCUS.R), ASCUS not otherwise specified (ASCUS.NOS) and ASCUS favor dysplasia (ASCUS.D) in adolescents were .13, .17 and .31, respectively. ASCUS.NOS (P = .01) and ASCUS.D (P = .007) were strong indicators of dysplasia as compared to ASCUS.R. CONCLUSION: PS abnormalities are more common in sexually active adolescents, with a significantly higher prevalence of LSIL over HSIL as compared to adult women. Given the natural history of HPV infection, we recommend follow-up with cytology rather than colposcopy/biopsy for adolescents with ASCUS and LSIL PSs. Qualification of ASCUS is useful in determining which adolescents are at the highest risk of cervical dysplasia.     

Blood-brain barrier Ca2+-ATPase cytochemistry: incubation media and fixation methods for differentiating Ca2+-specific ATPase from ecto-ATPase

It has been shown that infection with high-risk human papillomaviruses (HR-HPV) is related to the development of cervical cancer. The persistence of the virus in intra-epithelial lesions of cervix uteri (SILs) is the basis for the application of HPV testing for screening and management of patients. Most infections by HR-HPVs resolve spontaneously, however, and do not progress to dysplasia or cancer. p16INK4a is a useful biomarker of cervical intra-epithelial neoplasia and could be a marker for the progression of low-grade squamous intra-epithelial lesions (LSILs) to high-grade squamous intra-epithelial lesions (HSILs), because it correlates independently with increasing SIL grade. We conducted a preliminary histological study of 28 patients diagnosed with LSIL, HSIL or nondysplastic epithelium (NDE) from whom 28 biopsies of uterine cervix and 28 endocervical brushed biopsies were taken. Argyrophilic nucleolar organizer region (AgNOR) and p16INK4a assays were performed on the biopsies, and endocervical brushings were used for HPV typing. The high risk HPV group showed that the number of patients with AgNOR areas greater than 3.3 µm² and with expression of p16INK4a were statistically greater than the number of lower risk patients. None of the biopsies of LR-HPV carriers expressed p16 and AgNOR areas> 3.3 μm² simultaneously. Four LSILs and the NDE of this group expressed neither of the two markers. If the correlation between AgNOR areas and p16INK4a is good, we may be able to develop a low cost simple technology for studying patients infected with HR-HPV and diagnosed with LSIL of uncertain behavior.