Uterine cervical stenosis: from classification to advances in management. Overcoming the obstacles to access the uterine cavity.

BACKGROUND: To date hysteroscopy is the gold standard technique for the evaluation and management of intrauterine pathologies. The cervical canal represents the access route to the uterine cavity. The presence of cervical stenosis often makes entry into the uterine cavity difficult and occasionally impossible. Cervical stenosis has a multifactorial etiology. It is the result of adhesion processes that can lead to the narrowing or total obliteration of the cervical canal. PURPOSE: In this review, we summarize the scientific evidence about cervical stenosis, aiming to identify the best strategy to overcome this challenging condition. METHODS: The literature review followed the scale for the quality assessment of narrative review articles (SANRA). All articles describing the hysteroscopic management of cervical stenosis were considered eligible. Only original papers that reported data on the topic were included. RESULTS: Various strategies have been proposed to address cervical stenosis, including surgical and non-surgical methods. Medical treatments such as the preprocedural use of cervical-ripening agents or osmotic dilators have been explored. Surgical options include the use of cervical dilators and hysteroscopic treatments. CONCLUSIONS: Cervical stenosis can present challenges in achieving successful intrauterine procedures. Operative hysteroscopy has been shown to have the highest success rate, particularly in cases of severe cervical stenosis, and is currently considered the gold standard for managing this condition. Despite the availability of miniaturized instruments that have made the management of cervical stenosis more feasible, it remains a complex task, even for experienced hysteroscopists.

Uterine Artery Pseudoaneurysm in a Pregnant Patient with Retrocervical Endometriosis.

A pseudoaneurysm of the uterine artery or its branches is usually a result of vascular trauma during invasive procedures such as a cesarean section, vaginal delivery, myomectomy, hysterotomy, or dilatation and curettage. A uterine artery pseudoaneurysm rupture is a rare, yet life-threatening event. Deep infiltrating endometriosis usually involves a decrease in symptoms and imaging findings throughout pregnancy, with the notable exception of the phenomenon of decidualization. We present the case of a pregnant woman with a recent diagnosis of endometriosis, who conceived spontaneously and presented with disabling pain at 13 weeks' gestation. She was diagnosed with a left, huge (and rapidly growing) retrocervical endometriosis nodule encompassing a uterine artery pseudoaneurysm. Selective transarterial embolization was performed at 22 weeks' gestation owing to enlargement of the pseudoaneurysm sac, and the pseudoaneurysm was obliterated successfully. The patient was followed intensively throughout the pregnancy and the baby was delivered at term by cesarean section. After delivery, the nodule returned to the pregestational size.

Primary localized amyloidosis of the uterine cervix during pregnancy.

Amyloidosis of the uterine cervix is rare. A 35-year-old pregnant woman underwent a cervical biopsy and was found to have amyloid deposits. The results of liquid chromatography-tandem mass spectrometry revealed that these deposits mainly consisted of immunoglobulin light chain (kappa chain). After undergoing several examinations, the patient was diagnosed with localized amyloidosis, without systemic or secondary amyloidosis. She underwent a normal delivery without disease exacerbation. The possible presence of systemic and secondary amyloidosis must be evaluated carefully during the diagnosis of localized cervical amyloidosis.

Molecular detection of Mycoplasma genitalium in endocervical swabs and associated rates of macrolide and fluoroquinolone resistance in Hong Kong.

INTRODUCTION: There is a global trend of increasing macrolide and fluoroquinolone resistance in Mycoplasma genitalium (MG), such that international guidelines recommend molecular detection of resistance if a patient has MG-positive test results. Tests for MG are not routinely performed in Hong Kong. This study examined the detection of MG in endocervical swabs and the associated macrolide and fluoroquinolone resistance rates. METHODS: Endocervical swabs received from two sexual health clinics in Hong Kong for routine assessments of Chlamydia trachomatis and Neisseria gonorrhoeae were also subjected to detection of MG. All MG-positive samples were tested for resistance-mediating mutations in 23S rRNA, parC, and gyrA genes. Laboratory records and past results for each patient were analysed. RESULTS: In total, endocervical swabs from 285 patients were included in this study. Mycoplasma genitalium was detected in swabs from 21 patients (7.4%) by real-time polymerase chain reaction with a commercial kit. Among MG-positive samples which were successfully analysed further, macrolide resistance-mediating mutations in 23S rRNA were found in 42.1% (8/19); fluoroquinolone resistance-related mutations in parC and gyrA were found in 65% (13/20) and 0% (0/20), respectively. All macrolide-resistant MG strains were also fluoroquinolone-resistant (42.1%, 8/19). No assessed factors were associated with the detection of MG or resistance-related mutations. CONCLUSION: In Hong Kong, MG was detected in endocervical swabs from 7.4% of patients in sexual health clinics, with high rates of macrolide and fluoroquinolone resistance. These findings warrant careful review of testing, clinical correlation, and treatment strategies for MG in the context of increasing antibiotic resistance.

Hyperelastic Ex Vivo Cervical Tissue Mechanical Characterization.

This paper presents the results of the comparison between a proposed Fourth Order Elastic Constants (FOECs) nonlinear model defined in the sense of Landau's theory, and the two most contrasted hyperelastic models in the literature, Mooney-Rivlin, and Ogden models. A mechanical testing protocol is developed to investigate the large-strain response of ex vivo cervical tissue samples in uniaxial tension in its two principal anatomical locations, the epithelial and connective layers. The final aim of this work is to compare the reconstructed shear modulus of the epithelial and connective layers of cervical tissue. According to the obtained results, the nonlinear parameter A from the proposed FOEC model could be an important biomarker in cervical tissue diagnosis. In addition, the calculated shear modulus depended on the anatomical location of the cervical tissue (µepithelial = 1.29 ± 0.15 MPa, and µconnective = 3.60 ± 0.63 MPa).

Emergent genital infection by Leptotrichia trevisanii.

We report the first case of an association between Leptotrichia trevisanii and an episode of pelvic inflammatory disease (PID) and the second case of the isolation of this infection in the cervical canal. A 45-yr-old woman was admitted to our emergency department with clinical and radiological signs and symptoms compatible with an episode of PID. She was hospitalized for intravenous antibiotic control and treatment and the subsequent surgical drainage of abscesses. Cultures were taken throughout the process, but only cultures from cervical canal exudate were positive, with the growth of L. trevisanii species. It appears important to carry out a complete microbiological screening, not limited to conventional agents, on adequate clinical samples to detect possible infectious agents that may be missed in these cases.

Vaginoscopy Against Standard Treatment: a randomised controlled trial.

OBJECTIVE: To evaluate whether vaginoscopy or standard hysteroscopy was more successful in the outpatient setting. DESIGN: Randomised controlled multicentre trial. SETTING: Outpatient hysteroscopy clinics at two UK hospitals. POPULATION: 1597 women aged 16 or older undergoing an outpatient hysteroscopy. METHODS: Women were allocated to vaginoscopy or standard hysteroscopy using third party randomisation stratified by menopausal status with no blinding of participants or clinicians. MAIN OUTCOME MEASURES: The primary outcome was 'success', a composite endpoint defined as: a complete procedure, no complications, a level of pain acceptable to the patient, and no sign of genitourinary tract infection 2 weeks after the procedure. RESULTS: Vaginoscopy was significantly more successful than standard hysteroscopy [647/726 (89%) versus 621/734 (85%), respectively; relative risk (RR) 1.05, 95% CI 1.01-1.10; P = 0.01]. The median time taken to complete vaginoscopy was 2 minutes compared with 3 minutes for standard hysteroscopy (P < 0.001). The mean pain score was 42.7 for vaginoscopy, which was significantly less than standard hysteroscopy 46.4 (P = 0.02). Operative complications occurred in five women receiving vaginoscopy and 19 women receiving standard hysteroscopy (RR 0.26, 95% CI 0.10-0.69). CONCLUSIONS: Vaginoscopy is quicker to perform, less painful, and more successful than standard hysteroscopy and therefore should be considered the technique of choice for outpatient hysteroscopy. TWEETABLE ABSTRACT: Vaginoscopy is quicker to perform, less painful, and more successful than standard hysteroscopy.

Uterine cervical ulceration caused by group C streptococcal infection during pregnancy: A case report.

Causes of cervical ulceration include infection, collagen disease, malignant tumors and external stimuli. Cervical ulceration during pregnancy is rare. We present a case of cervical ulceration caused by group C streptococcal infection during pregnancy. A 36-year-old woman (gravida 1, para 0) complained of metrorrhagia, and a circular cervical ulcer of about 1.5 cm in diameter was detected on her cervix at 37 weeks' gestation. A biopsy and a cultivation test of the ulcer were performed, and pathological diagnosis was made as suppurative inflammation, and group C streptococcal infection was detected by the cultivation test. The ulcer had expanded to about 3 cm in diameter at the onset of labor at 40 weeks' gestation. An emergency cesarean section was performed because of failed induction of labor, and she was delivered of a male baby. The ulcer became gradually smaller after delivery, and completely disappeared on the 35th day after delivery.

Portable Pocket colposcopy performs comparably to standard-of-care clinical colposcopy using acetic acid and Lugol's iodine as contrast mediators: an investigational study in Peru.

OBJECTIVE: Our goal was to develop a tele-colposcopy platform for primary-care clinics to improve screening sensitivity and access. Specifically, we developed a low-cost, portable Pocket colposcope and evaluated its performance in a tertiary healthcare centre in Peru. DESIGN AND SETTING: Images of the cervix were captured with a standard-of-care and Pocket colposcope at la Liga Contra el Cáncer in Lima, Peru. POPULATION: Two hundred Peruvian women with abnormal cytology and/or human papillomavirus positivity were enrolled. METHODS: Images were collected using acetic acid and Lugol's iodine as contrast agents. Biopsies were taken as per standard-of-care procedures. MAIN OUTCOME MEASURES: After passing quality review, images from 129 women were sent to four physicians who provided a diagnosis for each image. RESULTS: Physician interpretation of images from the two colposcopes agreed 83.1% of the time. The average sensitivity and specificity of physician interpretation compared with pathology was similar for the Pocket (sensitivity = 71.2%, specificity = 57.5%) and standard-of-care (sensitivity = 79.8%, specificity = 56.6%) colposcopes. When compared with a previous study where only acetic acid was applied to the cervix, results indicated that adding Lugol's iodine as a secondary contrast agent improved the percent agreement between colposcopes for all pathological categories by up to 8.9% and the sensitivity and specificity of physician interpretation compared with pathology by over 6.0 and 9.0%, respectively. CONCLUSIONS: The Pocket colposcope performance was similar to that of a standard-of-care colposcope when used to identify precancerous and cancerous lesions using acetic acid and Lugol's iodine during colposcopy examinations in Peru. TWEETABLE ABSTRACT: The Pocket colposcope performance was similar to that of a standard-of-care colposcope when identifying cervical lesions.

Bivariate random-effects meta-analysis models for diagnostic test accuracy studies using arcsine-based transformations.

Diagnostic or screening tests are widely used in medical fields to classify patients according to their disease status. Several statistical models for meta-analysis of diagnostic test accuracy studies have been developed to synthesize test sensitivity and specificity of a diagnostic test of interest. Because of the correlation between test sensitivity and specificity, modeling the two measures using a bivariate model is recommended. In this paper, we extend the current standard bivariate linear mixed model (LMM) by proposing two variance-stabilizing transformations: the arcsine square root and the Freeman-Tukey double arcsine transformation. We compared the performance of the proposed methods with the standard method through simulations using several performance measures. The simulation results showed that our proposed methods performed better than the standard LMM in terms of bias, root mean square error, and coverage probability in most of the scenarios, even when data were generated assuming the standard LMM. We also illustrated the methods using two real data sets.

Quantitative Measurement of L1 Human Papillomavirus Type 16 Methylation for the Prediction of Preinvasive and Invasive Cervical Disease.

Background: Methylation of the human papillomavirus (HPV) DNA has been proposed as a novel biomarker. Here, we correlated the mean methylation level of 12 CpG sites within the L1 gene, to the histological grade of cervical precancer and cancer. We assessed whether HPV L1 gene methylation can predict the presence of high-grade disease at histology in women testing positive for HPV16 genotype. Methods: Pyrosequencing was used for DNA methylation quantification and 145 women were recruited. Results: We found that the L1 HPV16 mean methylation (±SD) significantly increased with disease severity (cervical intraepithelial neoplasia [CIN] 3, 17.9% [±7.2] vs CIN2, 11.6% [±6.5], P < .001 or vs CIN1, 9.0% [±3.5], P < .001). Mean methylation was a good predictor of CIN3+ cases; the area under the curve was higher for sites 5611 in the prediction of CIN2+ and higher for position 7145 for CIN3+. The evaluation of different methylation thresholds for the prediction of CIN3+ showed that the optimal balance of sensitivity and specificity (75.7% and 77.5%, respectively) and positive and negative predictive values (74.7% and 78.5%, respectively) was achieved for a methylation of 14.0% with overall accuracy of 76.7%. Conclusions: Elevated methylation level is associated with increased disease severity and has good ability to discriminate HPV16-positive women that have high-grade disease or worse.

Co-infection of sexually transmitted pathogens and Human Papillomavirus in cervical samples of women of Brazil.

BACKGROUND: Some sexually transmitted infectious agents, such as Chlamydia trachomatis and Herpes simplex, cause local inflammation, and could contribute to Human Papillomavirus (HPV) and cervical lesion progression. Thus, the aim of this study was to determine any association between the presence of microorganisms of gynecological importance, sexual behavior, clinical and demographical variables to the development and progress of cervical lesions. METHODS: One hundred and thirty-two women between 14 and 78 years and living at Vitória da Conquista, Bahia, Brazil, were included (62 individuals with cervical lesions and 70 without lesions). They answered a questionnaire to provide data for a socioeconomic and sexual activity profile. Samples of cervical swabs were collected and analyzed by PCR to detect genital microorganisms and HPV. Quantitative PCR was used to detect and quantify Ureaplasma urealyticum and Ureaplasma parvum. Univariate and multiple logistic regression were performed to measure the association with the cervical lesions, and an odds ratio (OR) with 95% confidence intervals (95%CI) were calculated. The Mann-Whitney U test was also used to compare the microorganism load in the case and control groups. The significance level was 5% in all hypotheses tested. RESULTS: Cervical lesions were associated with: women in a stable sexual relationship (OR = 14.21, 95%CI = 3.67-55.018), positive PCR for HPV (OR = 16.81, 95%CI = 4.19-67.42), Trichomonas vaginalis (OR = 8.566, 95%CI = 2.04-35.94) and Gardnerella vaginalis (OR = 6.13, 95%CI = 1.53-24.61), adjusted by age and qPCR for U. parvum. U. parvum load showed a statistical difference between the case and control groups (p-value = 0.002). CONCLUSION: Variables such as stable relationship, HPV, T. vaginalis, G. vaginalis were associated with cervical lesions in epidemiological studies. U. parvum load was higher in woman with cervical lesions compared with women without lesions. Additional studies are needed to better understand the role of these factors in cervical lesion development.

Using novel biomarkers to triage young adult women with minor cervical lesions: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the short-term consequences and cost-effectiveness associated with the use of novel biomarkers to triage young adult women with minor cervical cytological lesions. DESIGN: Model-based economic evaluation using primary epidemiological data from Norway, supplemented with data from European and American clinical trials. SETTING: Organised cervical cancer screening in Norway. POPULATION: Women aged 25-33 years with minor cervical cytological lesions detected at their primary screening test. METHODS: We expanded an existing simulation model to compare 12 triage strategies involving alternative biomarkers (i.e. reflex human papillomavirus (HPV) DNA/mRNA testing, genotyping, and dual staining) with the current Norwegian triage guidelines. MAIN OUTCOME MEASURES: The number of high-grade precancers detected and resource use (e.g. monetary costs and colposcopy referrals) for a single screening round (3 years) for each triage strategy. Cost-efficiency, defined as the additional cost per additional precancer detected of each strategy compared with the next most costly strategy. RESULTS: Five strategies were identified as cost-efficient, and are projected to increase the precancer detection rate between 18 and 57%, compared with current guidelines; however, the strategies did not uniformly require additional resources. Strategies involving HPV mRNA testing required fewer resources, whereas HPV DNA-based strategies detected >50% more precancers, but were more costly and required twice as many colposcopy referrals compared with the current guidelines. CONCLUSION: Strategies involving biomarkers to triage younger women with minor cervical cytological lesions have the potential to detect additional precancers, yet the optimal strategy depends on the resources available as well as decision-makers' and women's acceptance of additional screening procedures. TWEETABLE ABSTRACT: Women with minor cervical lesions may be triaged more accurately and effectively using novel biomarkers.

Health-related quality of life as measured by the EQ-5D in the prevention, screening and management of cervical disease: A systematic review.

PURPOSE: Cost-effectiveness analyses (CEAs) of screening can be highly sensitive to the health-related quality of life (HRQoL) effects of screen tests and subsequent treatment. Accordingly, accurate assessment of HRQoL is essential. We reviewed the literature regarding HRQoL in cervical prevention and management in order to appraise the current evidence regarding this important input to CEA. METHODS: We searched the MEDLINE, Scopus and EconLit databases for studies that estimated HRQoL in cervical cancer prevention and management published January 1995-December 2015. The primary inclusion criterion was for studies that assess HRQoL using the EQ-5D. Data were abstracted from eligible studies on setting, elicitation group, sample size, elicitation instruments, health state valuations, study design and follow-up. We assessed the quality and comparability of the studies with a particular focus on the HRQoL reported across states and groups. RESULTS: Fifteen papers met the inclusion criteria. Most used patient elicitation groups (n = 11), 2 used the general public and 2 used a mix of both. Eight studies were cross-sectional and seven were longitudinal. Six studies used both the EQ-5D-3L and the EQ-VAS together with other measures of overall HRQoL or condition-specific instruments. Extensive heterogeneity was observed across study characteristics. CONCLUSIONS: Our results reveal the challenges of sourcing reliable estimates of HRQoL for use in CEAs of cervical cancer prevention and treatment. The EQ-5D appears insufficiently sensitive for some health states. A more general problem is the paucity of HRQoL estimates for many health states and their change over time.

Comparison of Keyes Punch Biopsy Instrument with Cervical Punch Biopsy Forceps for Diagnosing Cervical Lesions.

OBJECTIVE: To assess the feasibility and efficacy of Keyes punch biopsy instrument (KP) in diagnosing cervical lesions and compare it with cervical punch biopsy forceps (CP). METHODS: 75 women having satisfactory colposcopy with abnormal transformation zone were included and paired colposcopic directed biopsies were taken using KP followed by CP from the same target area. RESULTS: It was feasible in all cases to take cervical biopsy with KP after increasing its effective length. The volume of gross specimen obtained by KP was less than CP (0.076 ± 0.097 vs. 0.101 ± 0.156 cm3, p = 0.061), however on microscopic examination, mean length and mean depth of tissue in KP was greater than CP by 0.06 mm (p = 0.810) and 0.14 mm (p = 0.634) respectively. Exact agreement was found with the final surgical specimen in 42% of cases in both the biopsy forceps. CONCLUSION: KP is almost at par with CP for diagnosing preinvasive cervical lesions and is a useful adjunct to the existing armamentarium of biopsy forceps.

Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.

Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer.

Barriers to Cervical Screening Among Sex Workers in Vancouver.

OBJECTIVES: We longitudinally examined the social, structural, and geographic correlates of cervical screening among sex workers in Metropolitan Vancouver, British Columbia, to determine the roles that physical and social geography play in routine reproductive health care access. METHODS: Analysis drew on (2010-2013) data from an open prospective cohort of sex workers (An Evaluation of Sex Workers' Health Access). We used multivariable logistic regression with generalized estimating equations (GEE) to model correlates of regular cervical screening. RESULTS: At baseline, 236 (38.6%) of 611 sex workers in our sample had received cervical screening, and 63 (10.3%) were HIV-seropositive. In multivariable GEE analysis, HIV-seropositivity (adjusted odds ratio [AOR] = 1.65; 95% confidence interval [CI] = 1.06, 2.58) and accessing outreach services (AOR = 1.35; 95% CI = 1.09, 1.66) were correlated with regular cervical screening. Experiencing barriers to health care access (e.g., poor treatment by health care staff, limited hours of operation, and language barriers) reduced odds of regular Papanicolaou testing (AOR = 0.81; 95% CI = 0.65, 1.00). CONCLUSIONS: Sex workers in Metropolitan Vancouver had suboptimal levels of cervical screening. Innovative mobile outreach service delivery models offering cervical screening as one component of sex worker-targeted comprehensive sexual and reproductive health services may hold promise.

Endocervical Polyp With Florid "Epidermal Metaplasia": Report of a Previously Undescribed Phenomenon.

Endocervical polyps are common benign lesions which rarely result in diagnostic problems, although a variety of alterations occasionally complicate histologic interpretation. We report an unusual, and not previously described, finding of florid "epidermal" metaplasia with keratinization and extensive formation of skin appendages structures (sebaceous and sweat glands and hair follicles) within an endocervical polyp. The features closely resembled an epidermal inclusion cyst. We speculate on the possible pathogenesis of this rare phenomenon and review unusual findings in endocervical polyps.

US of the Nongravid Cervix with Multimodality Imaging Correlation: Normal Appearance, Pathologic Conditions, and Diagnostic Pitfalls.

The adult uterine cervix may exhibit a wide variety of pathologic conditions that include benign entities (eg, cervicitis, hyperplasia, nabothian cysts, cervical polyps, leiomyomas, endometriosis, and congenital abnormalities) as well as malignant lesions, particularly cervical carcinoma. In addition, lesions that arise in the uterine body may secondarily involve the cervix, such as endometrial carcinoma and prolapsed intracavitary masses. Many of these conditions can be identified and characterized at ultrasonography (US), which is considered the first-line imaging examination for the female pelvis. However, examination of the cervix is often cursory during pelvic US, such that cervical disease may be overlooked or misdiagnosed. Transabdominal US of the cervix may not afford sufficient spatial resolution to depict cervical disease in many patients; therefore, endovaginal US is considered the optimal technique. Use of supplemental imaging techniques, particularly the application of transducer pressure on the cervix, may be helpful. This review describes the normal appearance of the cervix at US, the appearance of cervical lesions and conditions that mimic abnormalities at US, and optimal US techniques for evaluation of the cervix. This information will help radiologists detect and diagnose cervical abnormalities more confidently at pelvic US. Online supplemental material is available for this article.