Human papillomavirus infection and cervical intraepithelial neoplasia in women with renal allografts.

An increased prevalence of cervical cancer has been observed in immunosuppressed women, but controlled studies are rare. Biopsy specimens from 49 women with renal allografts and 69 non-immunosuppressed controls (with no history of cervical intraepithelial neoplasia, vulval warts, or abnormal results of cervical smear tests) were assessed for colposcopic appearance, cytological and histological diagnosis, and the presence of human papillomavirus types 6/11 and 16/18 DNA sequences. At colposcopy 26 (53%) of the women with allografts had cervical abnormalities compared with 20 (29%) of the controls. The prevalence of cervical intraepithelial neoplasia was significantly higher in the women with allografts (24 (49%) compared with 7 (10%]. The overall rate of detection of human papillomavirus DNA did not differ significantly between the two groups. There was however, a significant difference in the rate of detection of human papillomavirus type 16/18 DNA (27% in the women with allografts and 6% in the controls). These data confirm that pathological and virological changes affecting the cervix are significantly increased in immunosuppressed women and emphasise the need for regular colposcopic examination.     

Conservative management of intraepithelial cervical neoplasia.

In a prospective trial cryotherapy was performed in 164 patients with preinvasive cervical neoplasia, most of whom desired future childbearing. Their disease had been evaluated by repeat cytology, colposcopy and colposcopically directed punch biopsies, with endocervical curettage when necessary. This conservative treatment eradicated the disease in 147 (89.6%) of the patients. The remaining 17 underwent complete reinvestigation. The focal residual disease in 12 was successfully treated by conservative means--repeat cryotherapy, focal electrocautery or punch biopsy. The other five required either cone biopsy or hysterectomy because of more extensive lesions.     

Cytologic predictors of cervical intraepithelial neoplasia in women with an ASCUS Pap smear

OBJECTIVE: To identify cytologic parameters on Pap smears of women with an atypical squamous cells of undetermined significance (ASCUS) diagnosis that could help cytologists to indicate whether a particular ASCUS case is most likely related to cervical intraepithelial neoplasia (CIN) grade 1 or 2/3. STUDY DESIGN: A total of 360 eligible women diagnosed with ASCUS and referred to the colposcopy clinic of Saint-Sacrement Hospital participated in the study. Eligible women were those aged 18-50 years, newly diagnosed with ASCUS, with no history of cervical biopsies or treatment, and not pregnant at the time of the visit. Colposcopically directed biopsies of lesions were obtained. All Pap smears were reviewed according to 36 different cytomorphologic criteria. The regression logistic model was used to estimate the odds ratios (ORs) for the associations between cytologic criteria observed in smears and the diagnosis of CIN made on biopsies. All cytologic criteria significantly (P < .05) associated with CIN were entered in the models, and a backward selection was done to determine independent cytologic predictors of CIN 1 and 2/3. RESULTS: Biopsies revealed that 22.2% of the study population had concurrent CIN. CIN I and 2/3 were identified in 61 (16.9%) and 19 women (5.3%), respectively. Clear perinuclear spaces (OR = 2.5, P = .002) and moderate nuclear atypia (OR = 4.4, P = .02) were two cytologic criteria independently associated with CIN 1. Four independent predictors of CIN 2/3 were identified: the presence of clear perinuclear spaces (OR = 5.9, P = .004), hyperchromasia (OR = 3.9, P = .04), moderate anisokaryosis (OR = 13.1, P = .01 and increased nuclear volume of metaplastic cells (OR = 5.1, P = .007). CONCLUSION: These observations may help cytologists to better categorize ASCUS lesions as intraepithelial ones and will also contribute to improving the Bethesda definition of ASCUS. Further studies are planned to validate these observations.     

DNA changes in progressive cervical intraepithelial neoplasia.

Cervical intra-epithelial neoplasm (CIN) is treated as a progressive lesion, even though most CIN will not progress to invasive cancer if left untreated. This study focussed on DNA-cytometric analysis of cytologic smears of patients who had developed invasive cancer after initial smears showing CIN. The first part of the study aimed at describing the DNA-cytometric changes in these progressive ('malignant') CIN lesions. In the second part a cluster analysis was performed on 'malignant' CIN III lesions and CIN III lesions, with 'unknown' malignant potential. The results indicated that 'malignant' CIN lesions developed high DNA-index (DI) values during malignant transformation, as demonstrated by increasing mean DI values, a high percentage of DNA-aneuploidy and 2.5c Exceeding Rates. Furthermore, a trend-like pattern of texture feature values occurred in 'malignant' CIN lesions with increasing severity. These findings provide objective quantitative confirmation of the evolution of nuclear changes during malignant transformation. Cluster analysis showed that it was possible, using a set of four cytometric features, to subdivide the 'unknown' CIN III lesions into a cluster of lesions with feature values similar to the vast majority of the 'malignant' CIN III lesions, and a second cluster of lesions with feature values dissimilar to 'malignant' CIN III. It is argued that the profile of 'malignant' CIN has become clearer and that the results of this study may serve as a basis for a more objective cytopathologic subdivision of premalignant CIN. It may be justified to follow up patients whose lesions do not yet fit this 'malignant' profile. Not treating the non-progressive lesion group will avoid putting these patients at risk.     

Human papillomavirus and cervical intraepithelial neoplasia in women who subsequently had invasive cancer.

In a retrospective case-control study biopsy specimens of cervical intraepithelial neoplasia (CIN) lesions from 47 women in whom invasive cancer subsequently developed (cases) and from 94 control subjects in whom CIN was diagnosed within 6 months of the diagnosis for the matched case subject but invasive disease did not develop were tested for human papillomavirus (HPV) DNA with tissue in-situ hybridization. There were no significant differences in the frequency of detection of HPV DNA between the two groups. In a cross-sectional survey the prevalence of HPV DNA was found to be 11% in specimens without CIN, 27% in those with CIN I, 49% in those with CIN II and 56% in those with CIN III. The positivity rates for HPV 16/33 DNA increased with the severity of CIN, but this was not observed for HPV 6/11 and 18 DNA. A comparison of the results of the case-control and cross-sectional studies suggested that the younger cohort of women had higher prevalence rates of HPV DNA than the older cohort.     

Presence of human papillomavirus DNA sequences in cervical intraepithelial neoplasia.

Twenty two patients referred to a district colposcopy clinic because of an abnormal cervical cytology report or a suspicious cervix and found to have a cervical epithelial abnormality were studied. The techniques of cytology, histology, immunohistochemistry, and DNA-DNA hybridisation were used to detect infection by human papillomavirus. Using an indirect immunoalkaline phosphatase technique human papillomavirus antigen was found in biopsy specimens from six of the 22 patients and DNA of papillomavirus type 6 in biopsy specimens from 13 of these women, including four out of six whose histological diagnosis was cervical intraepithelial neoplasia grade 3. In eight cases where cytological, colposcopical, and histological investigations all indicated the presence of wart virus infection, papillomavirus type 6 DNA was found in seven. Papillomavirus type 6 DNA was found in more than half of the proved cases of cervical intraepithelial neoplasia. The presence of this viral DNA in women with no cervical abnormality is to be studied.     

Diagnosis and treatment of cervical intraepithelial neoplasia in general practice.

OBJECTIVE--To audit the first five years of a colposcopy and treatment service for cervical dysplasia established within a general practice. DESIGN--A cervical smear register was established to determine which women were "at risk" of dysplasia. The results of colposcopy and treatment of dysplasia were analysed. SETTING--A large rural general practice with community hospital facilities in mid-Wales. PATIENTS--4437 Women at risk in a total practice population of 14,100. INTERVENTIONS--Colposcopy of women with dyskaryotic smear results, persistent inflammatory smear results, or vulval warts. Treatment of women with proved dysplasia by electrodiathermy of the cervix or cone biopsy. RESULTS--138 Women with dysplasia were diagnosed over five years: 36 mild, 97 moderate or severe, and five with microinvasion. Despite a 78% smear rate of at risk women over five years, nine invasive cancers still occurred. CONCLUSIONS--The results of treatment are acceptable. Cervical dysplasia has become very common, the risk of a dysplasia in women aged 20-39 who had smear tests being one in 14 over five years.     

Langerhans' cells and subtypes of human papillomavirus in cervical intraepithelial neoplasia.

There is strong circumstantial evidence that human papillomavirus is a cofactor in the development of cervical neoplasia. Systemic immunosuppression has also been implicated. A study was therefore carried out examining the relation between subtypes of human papillomavirus and local immunocompetent cells in the cervix. Colposcopically directed punch biopsy specimens were taken from normal cervix and from histologically proved cervical intraepithelial neoplasia for immunohistochemical studies. Human papillomavirus genome probing was performed on the abnormal specimens. A relation was apparent between decreased Langerhans'' cells and moderate to high copy numbers of human papillomavirus type 16. The reduction in Langerhans'' cells was significant for human papillomavirus type 18 even at low copy numbers. Conversely, the absence of human papillomavirus was associated with increased numbers of Langerhans'' cells in cervical intraepithelial neoplasia. These findings suggest that the proposed oncogenic potential of human papillomavirus type 16 and human papillomavirus type 18 in particular may be mediated by a specific effect on the afferent limb of the immune response.     

Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia.

To assess the variability among histopathologists in diagnosing and grading cervical intraepithelial neoplasia eight experienced histopathologists based at different hospitals examined the same set of 100 consecutive colposcopic cervical biopsy specimens and assigned them into one of six diagnostic categories. These were normal squamous epithelium, non-neoplastic squamous proliferations, cervical intraepithelial neoplasia grades I, II, and III, and other. The histopathologists were given currently accepted criteria for diagnosing and grading cervical intraepithelial neoplasia and asked to mark their degree of confidence about their decision on a visual linear analogue scale provided. The degree of agreement between the histopathologists was characterised by kappa statistics, which showed an overall poor agreement (unweighted kappa 0.358). Agreement between observers was excellent for invasive lesions, moderately good for cervical intraepithelial neoplasia grade III, and poor for cervical intraepithelial neoplasia grades I and II (unweighted kappa 0.832, 0.496, 0.172, and 0.175, respectively); the kappa value for all grades of cervical intraepithelial neoplasia taken together was 0.660. The most important source of disagreement lay in the distinction of reactive squamous proliferations from cervical intraepithelial neoplasia grade I. The histopathologists were confident in diagnosing cervical intraepithelial neoplasia grade III and invasive carcinoma (other) but not as confident in diagnosing cervical intraepithelial neoplasia grades I and II and glandular atypia (other). Experienced histopathologists show considerable interobserver variability in grading cervical intraepithelial neoplasia and more importantly in distinguishing between reactive squamous proliferations and cervical intraepithelial neoplasia grade I. It is suggested that the three grade division of cervical intraepithelial neoplasia should be abandoned and a borderline category introduced that entails follow up without treatment.     

Risk factors associated with human papillomavirus prevalence and cervical neoplasia among Cameroonian women

BackgroundThis study used community-based cervical cancer screening for high-risk human-papillomavirus (HPV) to determine demographic and lifestyle factors associated with HPV prevalence and cervical intraepithelial neoplasia grade 2 or worse (CIN2+).MethodsWomen (n = 838) aged 25–65 years were recruited in two sequential studies in Cameroon. Demographic and historical data were obtained from participants and specimens were self-collected for HPV-testing using real-time PCR. HPV-positive women underwent biopsy and endocervical curettage. Associations were determined using bivariate analysis and logistic regression.ResultsHPV and self-reported HIV prevalence were 39.0% and 9.2%, respectively. Eighteen (9.3%) CIN2+ lesions were found among HPV-positive women. Housewives had a higher risk of being HPV infected (OR = 1.60, p = 0.010). HIV co-infection (aOR = 3.44, p < 0.001) and hormonal contraception (aOR = 1.97, p = 0.007) were associated with increased HPV prevalence. HPV-positive women who used condoms during sexual intercourse were at lower risk of CIN2+ (aOR = 0.15, p = 0.029). CIN2–3 lesions were found in women younger than 50 years, with a median age of 36 years (31–44). HPV-16/18-positive women had a 4.65-fold increased risk of CIN2+ (p = 0.015).ConclusionsYoung, single women and housewives were at higher risk of HPV infection. Preventive strategies for cervical cancer in low-resource settings should target women aged 30–50 years for HPV screening, and should focus treatment and follow-up on HPV-16/18-positive women. Further studies are needed to clarify if other risk factors require attention.     

宫颈上皮内瘤变与宫颈微生物群落结构的相关性

目的分析宫颈上皮内瘤变与宫颈微生物群落结构的相关性。方法选取2017年1月至2018年10月于我院就诊的253例女性进行回顾性分析,根据是否患有宫颈上皮内瘤变分为CIN组(86例)及对照组(167例)。采集纳入对象的宫颈菌群并提取细菌基因组DNA,对细菌16S rRNA V3、V4区片段进行PCR扩增,并采用Illuminate Miseq测序平台对PCR产物进行测序,分析两组对象宫颈微生物群落结构,并分析患者宫颈微生物群落结构与宫颈上皮内瘤变的相关性。结果两组对象宫颈微生物群落的Simpson指数及Shannon指数比较差异无统计学意义(t=1.474、1.636,P0.05),而CIN组的Chao指数及ACE指数均高于对照组(t=9.213、10.420,P0.05)。16S rRNA分析显示放线菌是宫颈部位的主要菌群。CIN组女性宫颈微生物群落中放线菌、奇异菌属、放线菌门、阴道奇异菌及奇异变形菌占主要优势(LDA4log10),对照组中杆菌、厚壁菌门等占主要优势。Spearman相关分析示卷曲乳杆菌、惰性乳杆菌、格氏乳杆菌、詹氏乳杆菌与宫颈上皮内瘤变呈负相关,而加特纳菌、阴道奇异菌、普雷沃氏菌、粪球菌与宫颈上皮内瘤变呈正相关(均P0.05)。结论 CIN女性宫颈菌群与健康女性存在明显差异,其中卷曲乳杆菌、惰性乳杆菌、格氏乳杆菌、詹氏乳杆菌与宫颈上皮内瘤变呈负相关,而加特纳菌、阴道奇异菌、普雷沃氏菌、粪球菌与宫颈上皮内瘤变呈正相关。     

Mean nuclear volume in cervical intraepithelial neoplasia and carcinoma

OBJECTIVE: To correlate three-dimensional nuclear size (mean nuclear volume) estimated by the stereologic intercept methodfor objective classification of cervical intraepithelial neoplasia (CIN) and carcinoma. STUDY DESIGN: In this retrospective study a total number of 29 CIN cases (8 cases of CIN 1, 10 cases of CIN 2 and 11 cases of CIN 3) and 10 cervical squamous cell carcinoma cases were selected. Mean nuclear volume (MNV) of all cases was measured with an image cytometer (Leica, Cambridge, England) using Quantimet 600 software (Leica). Nuclear point resection method was adopted to measure nuclear volume. Mean intercepted diameter of at least 50 nuclei was measured randomly. MNV was correlated with the histologic grade and diagnosis. RESULTS: MNV of CIN 1, 2, 3 and carcinoma cases was 291.72, 403.33, 711.45 and 893 microm3, respectively. ANOVA test results showed that MNV of CIN 1 and 2 was significantly lower than that of CIN 3 and invasive carcinoma (P < .000). MNV of CIN 3 was also significantly lower than that of carcinoma cases (P <.05). CONCLUSION: The findings suggest that estimates of MNV on conventional histopathology slides provide objective and useful criteria for relatively subjective histopathologic grading.