Severe Cervical Dysplasia Research Articles

Mandatory colposcopic findings of severe cervical dysplasia. Are there key-signs that need our special attention?

IntroductionTo test for colposcopic differences between CIN2+ and non CIN2+ lesions of the “major changes” of the RIO 2011 nomenclature of the International Federation of Cervical Pathology (IFCPC). Material and methodsRetrospective cohort analysis of colposcopic examinations of patients with histologically confirmed CIN2+ (n=99) and non CIN2+ (n=102) lesions during a four years period. Main outcome measures: leukoplakia, coarse mosaic and punctuation, dense acetowhitening, sharp boarders, ridge sign, atypical vessels. ResultsOnly coarse punctuation (P≤0.001; OR 9.64; 95% CI 2.15–43.13), coarse mosaic (P≤0.001; OR 4.00; 95% CI 1.83–8.73) and dense acetowhitening (P≤0.05; OR 1.86; 95% CI 1.06–3.26) occurred more frequently in CIN2+ lesions which were confirmed as predictors by a regression analysis. ConclusionsOnly coarse punctuation and coarse mosaic followed by dense acetowhitening as part of the “major changes” of the IFCPC Rio 2011 nomenclature achieve predictive values for CIN2+ lesions and should be therefore emphasized in colposcopy.

Cervical cytology pattern and human immunodeficiency virus serostatus of women seen in Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Background: Cervical cancer is the second most common cancer in women worldwide. Human immunodeficiency virus (HIV) has been suggested to be a cofactor in the association between human papillomavirus and cervical intraepithelial neoplasia (CIN). Aim: To determine the pattern of cervical cytology changes in women of different HIV status and characterise the sociodemographic factors that confound the changes seen. Methods: This was a cross-sectional comparative study. This study was conducted in Gynaecology Clinic of Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. Following informed consent, 272 HIV-positive (HIV+) and 275 HIV-negative (HIV−) women had questionnaires administered and Papanicolaou smears were taken. Results: The average age of the respondents was 32.6 ± 6.8 years (range: 15–49 years). Mean parity for HIV+ women was 3.28 and 3.36 for HIV− women while 70.8% of HIV+ women were married comparable with 72.7% in HIV− women. Twenty-nine per cent of HIV+ women had positive smears for CIN compared with 16.4% in those that were HIV−. This was statistically significant (odds ratio = 2.05, P = 0.001). The high-grade lesions (CIN II and CIN III) tended to be higher in the HIV+ women (11.4%) than the HIV− women (0.7%). Conclusion: HIV+ women in Zaria, Northern Nigeria, are at higher risk of severe cervical dysplasia compared with their counterparts who are HIV−. It is recommended that greater effort should be made to have an integrated reproductive healthcare service which includes cervical cytology within the HIV clinics.

Altered Salivary Protein Profiles among Individuals Diagnosed with Cervical Dysplasia and Cervical Carcinoma in Situ

Objective: The objective of this study was to determine if protein-by-products secondary to cervical cancer oncogenes appear in the saliva.Methods: Four pooled (n=10 subjects/pool) stimulated whole saliva specimens from women were analyzed. One pooled specimen was from healthy women, while other pooled specimens were from women diagnosed with CIN 2 moderate cervical dysplasia (n=10), CIN 3 severe cervical dysplasia (n=10) and the other pooled group from women diagnosed with cervical carcinoma in situ (n=10). Differential expression of proteins was measured by isotopically tagging proteins in each groups and comparing them to the healthy control group. Saliva from each of the pooled samples was trypsinized and the peptide digests labeled with the appropriate iTRAQ reagent. Labeled peptides from each of the digests were combined and analyzed by reverse phase (C18) capillary chromatography on an Applied Biosystems QStar LC-MS/MS mass spectrometer equipped with an LC-Packings HPLC.Results: The results of the salivary analyses yielded approximately 133 proteins in the saliva specimens. Forty eight proteins were differentially expressed between the healthy control pool, precancerous and cancerous conditions.Conclusions: The study suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be modulated secondary to precancerous and cancerous conditions and that these proteins may be useful in the study of cervical cancer progression, treatment efficacy and the tailoring of individualized patient care.

Efficiency of treatment in women with severe cervical dysplasia in different age periods

Efficiency of treatment in women with severe cervical dysplasia in different age periods

A population-based observational study comparing Cervista and Hybrid Capture 2 methods: improved relative specificity of the Cervista assay by increasing its cut-off.

BackgroundHigh-risk human papillomavirus (HR HPV) testing has been shown to be a valuable tool in cervical cancer screening for the detection of cervical pre-cancer and cancer.MethodsWe report a purely observational study evaluating HR HPV prevalences in residual liquid-based cytology (LBC) samples using both the Cervista™ HPV HR Test and the Digene Hybrid Capture 2 High-Risk HPV DNA Test (HC2) in a sample of 1,741 women aged ≥30 years of a German routine screening population of 13,372 women. Test characteristics were calculated and a novel method for measuring test performances was applied by calculating ratios of sensitivity or specificity.ResultsThe overall agreement of both tests for detection of HR HPV was excellent (κ = 0.8). Relative sensitivities for the detection of histologically confirmed severe cervical intraepithelial dysplasia (CIN3+) were similar for both HPV-tests, which was confirmed by the ratio analysis. However, discrepancy analysis between the Cervista HPV HR test and HC2 revealed a high false positive rate of the Cervista HPV HR test in the cytology normal category.ConclusionsPerformance of the Cervista HPV test in cervical specimens with abnormal cytology is comparable to HC2 as both tests were highly sensitive and specific for the detection of high grade cervical disease. We also demonstrate evidence that modification of the cut-off values drastically reduces the false positive rate in the cytology normal category without affecting the detection of CIN3+, which ultimately improved specificity of the Cervista HPV HR assay.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0674-1) contains supplementary material, which is available to authorized users.

RIO 2011: Mandatory colposcopic findings in diagnosis of severe cervical dysplasia

Objective: Current colposcopic nomenclature differs in minor, major and non-specific signs in the group of abnormal colposcopic findings. Study aim: Analysis of different aspects of major changes, comparing them to histologically confirmed severe dysplasia and thus to determine mandatory colposcopic findings of severe cervical dysplasia.

Obstetric and neonatal outcome after surgical treatment of cervical dysplasia

Conization is the gold standard today for the management of severe cervical dysplasia. However, with the increasing delay until first pregnancy, obstetric follow-up of patients with a history of conization is a growing concern. Retrospective case-control study using data from the electronic database of a university hospital. We compared the obstetric and neonatal outcome of 106 pregnancies delivered after conization with the outcome of 212 pregnancies of patients with no history of conization. A significant reduction in the mean gestational age at delivery (38.23 ± 2.51 weeks vs. 39.15 ± 1.56 weeks) was observed, together with a higher rate of premature rupture of the membrane (9.4% vs. 1.9%), premature onset of labor (9.4% vs. 2.4%), premature delivery (17% vs. 3.8%) and neonatal hospitalization (17.9% vs. 6.6%) in the group of patients with history of conization. Children born to women who had surgery had a significantly lower birth weight (3146.9 ± 611 g vs. 3347.3 ± 502 g) and size (49.1 ± 2.6 cm vs. 50.0 cm ± 2.2 cm) than those of the control group. Furthermore, these children were more frequently admitted in the neonatal intensive care unit (22.6% vs. 10.4%, p=0.004). Conization is an important risk factor for premature birth and women with a history of conization require cautious obstetric management during pregnancy. Anti-HPV vaccination and proactive surveillance of low-grade or moderate dysplasia, instead of immediate surgery, should be encouraged in young patients.

Treatment of Multifocal Bowen's Disease in Immunocompromised Women With Surgery and Topical Imiquimod

In human immunodeficiency virus (HIV)-infected women, Bowen's disease may be difficult to treat successfully with surgery alone. Imiquimod cream, effective in treating Bowen's disease in healthy women, may be a useful postsurgical treatment in immunocompromised women. Two HIV-infected women had both Bowen's disease and severe cervical dysplasia. In both cases, Bowen's disease, but not cervical dysplasia, recurred after surgical treatment. When treated with topical 5% imiquimod cream twice weekly for 4 months, 70-80% reduction in lesions were observed in both patients. Follow-up biopsies of remaining lesions were vulvar intraepithelial neoplasia 1. Imiquimod cream, in combination with surgical treatment, may be an appropriate strategy for treatment of Bowen's disease in HIV-infected and other immunocompromised women.

What are physician and patient factors important for proper follow-up of high-grade Pap smear abnormalities?

6103 Background: In order for expedited care to be provided to women with severe abnormalities on Pap smear, the physician should provide prompt triage of care and the patient should comply with follow-up care provided. This population-based study characterizes available physician and patient factors involved in the follow-up of abnormal Pap smear results. Methods: Women with a first time high grade diagnosis on Pap smear between 2000-2005 were identified utilizing a centralized cervical screening database. Databases containing information on healthcare delivery and physician practice characteristics in a setting of universal health care were linked utilizing patient and physician unique identifiers. Follow-up is defined as referral to colposcopy or any other procedure (Leep, Laser, etc) which can be associated with management of a severe cervical dysplasia. multivariate analysis followed by logistic regression was performed addressing follow-up as the dependant factor. Results: The study population contained 43,792 women with a first time high grade cervical abnormality. The loss to follow-up rate was 26%. Physician factors significantly associated with follow-up included practice duration of less than 5 years OR 1.28 CI (1.09-1.5);a nongynecologic practice was associated with lower follow-up, OR 0.69 CI (0.65-0.73). Patient factors associated with lower follow-up included older age 0.97 CI (0.97-0.98 and a lower comorbidity score 0.58 CI (0.48-0.7); a lower socioeconomic status was associated with a higher rate of follow-up OR 1.17 CI (1.1-1.2). Conclusions: While patient and physician factors impact appropriate follow-up for women with abnormal Pap smears, none of those captured have a high level of influence other than a gynecologic practice. In order to improve upon the high loss to follow-up rate, more information is needed on the practice settings of physicians and the screening program components and policies. No significant financial relationships to disclose.

Cervical Schistosomiasis as a Risk Factor of Cervical Uterine Dysplasia in a Traveler

Female genital schistosomiasis (FGS) may be under-recognized in endemic areas as a cause of cervical dysplasia, neoplasia, infertility, and as a facilitator of the transmission of HIV. To the best of our knowledge, few cases of FGS mimicking neoplasia have been reported in travelers. We report a clinical case of a 34-year-old white woman who presented with a severe cervical dysplasia, without any features of human papilloma virus infection, 2 years after bathing in a waterfall, a source of schistosomiasis, in Mali. Schistosomes eggs were found on the conization. Management included conization and medical treatment, resulting in a full clinical and histologic recovery. FGS should be kept in mind as a possible cause of cervical dysplasia in endemic areas. Medical treatment with praziquantel improves this condition.

Age and Prevalence of Cervical Carcinoma in Subsequent Hysterectomy Following a Conization Procedure

To determine the prevalence and age of patients with cervical carcinoma missed by a loop electrosurgical excision procedure. A total of 253 women with cervical dysplasia who underwent conization and 248 women who later underwent hysterectomy were retrospectively reviewed. The age and prevalence of those with cervical carcinoma diagnosed and missed by conization were determined. Of the 248 patients, 11 cases (4.4%) of cervical carcinoma were missed by cervical conization. The age of those with cervical carcinoma missed by conization was significantly greater than those whose diagnosis was not missed (p < 0.05). Women with severe cervical dysplasia who no longer wish to preserve fertility should be advised to undergo hysterectomy if the conization margins are not free of disease. Older women with incomplete resection margins tend to have undiagnosed hidden cervical carcinoma after cervical conization.

Women’s health—what’s new worldwide

Women’s health—what’s new worldwide

Cervical dysplasia among women over 35 years of age

The objective of the study was to review the cytologic and histopathologic features among women 35 years of age or older with cervical dysplasia. Patients presenting between 2001 and 2005 were included. Patients were labeled as pre- (PRE) or postmenopausal (POST) based on age younger than or 50 years old or older. Statistics were performed using SAS 8.0. Three hundred fifty-nine patients were identified: 270 PRE and 89 POST. PRE and POST patients had similar referral cytology with atypical cells of undetermined significance (ASC)/low-grade squamous intraepithelial lesion (LSIL) in 60% and 65% and high-grade squamous intraepithelial lesion (HSIL) in 35% and 27%, respectively. Among patients with ASC/LSIL, POST had significantly more cervical intraepithelial neoplasia (CIN) 3 (41% vs 29%; P = .027) as well as more malignancies (17 vs 0%; P = .002). Among patients referred for loop electrical excisional procedure secondary to HSIL cytology not explained by colposcopy, CIN 2 or greater was identified more often in POST (71 vs 32%; P = .03). Our data demonstrate a high proportion of severe cervical dysplasia in age groups traditionally thought to have less risk than younger patients.

Patterns of genotype distribution in multiple human papillomavirus infections

The relationship between severe-grade cervical lesions and clusters of human papillomavirus (HPV) genotypes in a taxonomic classification was surveyed in 232 women with previous abnormal cytology. HPV co-infections were clustered according to phylogenetic criteria. Multiple infections were detected in 22.0% of the entire sample. Clade A10 (represented by HPV-6 and HPV-11) appeared more frequently in multiple infections than clade A9, which was represented by five of the most common high-risk types, including HPV-16. Although HPV-16 was the most frequent genotype, it was not more prevalent in multiple infections. Abortion and two or more sexual partners were risk-factors associated with HPV co-infections. Severe cervical dysplasia was associated with co-infections with oncogenic types from different clades, with the association being significant for the high-risk clades A7 and A9.

Increased levels of HPV16 E6*I transcripts in high‐grade cervical cytology and histology (CIN II+) detected by rapid real‐time RT‐PCR amplification

As cervical dysplasia may regress to normal cytology or progress to cervical carcinoma, it would be valuable to have a diagnostic tool to help decide whether therapeutic conization should be performed. Cervical samples of 301 HPV16 positive women were collected in RNAlater reagent to prevent RNA degradation. Relative levels of HPV16 DNA and HPV16 E6*I mRNA in the samples were determined using real-time polymerase chain reaction. Findings were correlated with histological diagnoses and cytological follow-up. HPV16 E6*I mRNA levels were significantly higher in women with cytologically diagnosed severe cervical dysplasia (mean normalized ratio = 0.25) than in those with mild-to-moderate dysplasia (mean norm. ratio = 0.12), atypical squamous cells of uncertain origin (mean norm. ratio = 0.071) or normal cytology (mean norm. ratio = 0.034). Viral DNA levels were not significantly different between severe and mild-to-moderate dysplasia (mean norm. ratios, 55.8 and 63.5, respectively). The PPV for a histological diagnosis of severe cervical dysplasia [cervical intraepithelial neoplasia (CIN) II+] increased with the amounts of E6*I mRNA to more than 90% whereas the sensitivity decreased. The absence of HPV16 E6*I transcripts as well as HPV16 DNA considerably increased the negative predictive value and the specificity. However, low concentrations (or complete absence) of E6*I mRNA did not preclude a CIN II+ diagnosis. Although the sensitivity is low, high levels of HPV16 E6*I mRNA are indicative of CIN II+ in cytologically diagnosed cervical dysplasia of individual patients. Thus, quantification of HPV16 E6*I mRNA could be helpful in managing follow-up and treatment in a subset of HPV16 positive women.

A Randomized Double-Blind Placebo-Controlled Phase II Trial of the Cyclooxygenase-2 Inhibitor Celecoxib in the Treatment of Cervical Dysplasia

Abstract Objectives. The objective of the study was to evaluate the efficacy of daily Celecoxib in the regression of moderate and severe cervical dysplasia, when compared to placebo. Materials and methods. Women, over the age of 18, with the histologic diagnosis of moderate or severe cervical dysplasia were enrolled in this IRB approved study. Women were randomized to receive either Celecoxib 200 mg twice a day or placebo. Both examining physician and patients were blinded to treatment option. Follow-up colposcopy with cervical cytology was obtained at 2-month intervals for 6 months, with cytologic and histologic specimens. Results. From June 2002 until October 2003, a total of 25 patients were enrolled in this randomized phase II study. There was no statistical difference in screening entry criteria, clinical histologic and cytologic variables between the two groups. 60% of patients enrolled had an overall response in the trial. The mean time to response was 72 days. 75% of patients who received Celecoxib had a clinical response. This was significantly higher than the 31%, of the placebo patients that had a clinical response, P Conclusion. We have observed that Celecoxib could have activity in the treatment of high-grade cervical dysplasia. As a result, medical treatment of cervical dysplasia with Celecoxib could offer a minimally invasive treatment with minor morbidity and time constraints. Further trials with larger numbers are needed to confirm these results.

Immunohistochemical and molecular study of severe cervical dysplasia associated with HPV-83

Based on epidemiological data, infections with specific types of HPV can be classified as high-risk (HR), low-risk (LR) or intermediate-risk (IR) HPV depending on the risk of progression to cervical cancer. A 70-year-old woman consulted for relapse of abnormal cytology with high-grade squamous intraepithelial lesions (HSIL) associated with HPV-83 infection. Histological examination demonstrated high-grade cervical intraepithelial neoplasia (CIN III) with strong and diffuse staining by the P16(INK4a)-specific antibody. This patient's intermediate-risk HPV infection (HPV-83) rapidly progressed to severe cervical intraepithelial neoplasia (CIN III) with strong anti-P16(INK4a) immunolabelling. Analysis of the E6 peptide sequence revealed several mutations in one of the two putative zinc finger regions (AA residues 107-135) associated with p53 binding.

Daily celecoxib appears to have activity in the treatment of moderate and severe cervical dysplasia,

Daily celecoxib appears to have activity in the treatment of moderate and severe cervical dysplasia,

Cervical screening and management of cervical intraepithelial neoplasia in HIV-positive women

The high prevalence of abnormal cervical cytology in the context of immunosuppression has been recognized for many years. In response to repeated observations of cervical cancers in HIV-infected women, moderate and severe cervical dysplasia were designated as early symptomatic HIV infection (Category B) by the Centers for Disease Control and Prevention (CDC) in 1993, and invasive cervical cancer as an AIDS-defining condition (Category C). HIV-infected women, therefore, differ from the general population not only with a greater risk for more, but also potentially more severe cervical disease. In the era of highly active antiretroviral therapy, with HIV-infected women living for longer, there is a clear need to address this increased risk with appropriate management guidelines which this review attempts to provide.

A randomized double-blind placebo-controlled phase II trial of the cyclooxygenase-2 inhibitor Celecoxib in the treatment of cervical dysplasia

Objectives. The objective of the study was to evaluate the efficacy of daily Celecoxib in the regression of moderate and severe cervical dysplasia, when compared to placebo. Materials and methods. Women, over the age of 18, with the histologic diagnosis of moderate or severe cervical dysplasia were enrolled in this IRB approved study. Women were randomized to receive either Celecoxib 200 mg twice a day or placebo. Both examining physician and patients were blinded to treatment option. Follow-up colposcopy with cervical cytology was obtained at 2-month intervals for 6 months, with cytologic and histologic specimens. Results. From June 2002 until October 2003, a total of 25 patients were enrolled in this randomized phase II study. There was no statistical difference in screening entry criteria, clinical histologic and cytologic variables between the two groups. 60% of patients enrolled had an overall response in the trial. The mean time to response was 72 days. 75% of patients who received Celecoxib had a clinical response. This was significantly higher than the 31%, of the placebo patients that had a clinical response, P < 0.03. 33% of patients in the Celecoxib group had complete pathologic response to therapy, which was higher than the placebo group 15%. Conclusion. We have observed that Celecoxib could have activity in the treatment of high-grade cervical dysplasia. As a result, medical treatment of cervical dysplasia with Celecoxib could offer a minimally invasive treatment with minor morbidity and time constraints. Further trials with larger numbers are needed to confirm these results.