Which cervical sampler? A comparison of four methods

Four cytology sampling methods were compared in 1063 patients referred for colposcopy with a recent abnormal smear. A dyskaryotic smear of any grade was considered a positive result, though comparisons were limited to cases with a subsequent biopsy confirming CINII or III. There were no differences between the abilities of any of the four methods to detect higher grades of CIN (χ²₃=4.603, P >0.20). the presence or absence of endocervical cells in a smear was not significantly associated with any variation in success rate (χ²₁=0.959, P >0.30). the joint analysis of the four methods and the presence/absence of endocervical cells also showed no significant effects (χ²₇=12.768, 0.1 > P >0.05). In the latter analysis the trend towards a conventional level of significance was accounted for by the Aylesbury spatula giving a relatively high success rate when endocervical cells were present. the suggestion of advantage for the Aylesbury spatula merits further investigation.     

Extrasynaptic localization of α-bungarotoxin receptors in the rat superior cervical ganglion

Binding of [¹²⁵I]α-bungarotoxin to nicotinic cholinergic receptors (α-bungarotoxin receptors) was investigated in the rat superior cervical ganglion by light and electron microscope autoradiography. Both techniques indicated that labelling, which was inhibited by d-tubocurarine, occurred around and/or over neuronal perikarya. In particular, ultrastructural autoradiography showed that the synapses were devoid of radioactivity, suggesting that α-bungarotoxin receptors in the rat superior cervical ganglion are molecules distinct from the nicotinic (postsynaptic) receptors normally involved in ganglionic transmission. By contrast, specific labelling was found in extrasynaptic areas of the neuronal membrane in contact with satellite cells (neuron-satellite cell boundary). Quantitative analysis indicated that at that level silver grains were present on both the neuronal membrane and satellite cells. Furthermore, beside neuronal perikarya, radioactivity was also found around nerve fibres, probably in relation to both the axonal and interstitial sides of the ensheathing Schwann cells. Only a few grains were clearly accumulated inside nerve fibres. Finally, significant amounts of specific radioactivity were detected in the neuronal cytoplasm, especially at the level of rough endoplasmic reticulum and Golgi apparatus. However, parallel diffusion experiments with [¹²⁵I]α-bungarotoxin and [³H]inulin (a marker for the extracellular space) provided no evidence that the toxin enters the neuronal cytoplasm. Thus, the intraneuronal (specific) labeling was probably a reflection of α-bungarotoxin binding to membrane receptors and the subsequent internalization of the toxin-receptor complex in the neurons. We conclude that in the rat superior cervical ganglion extrasynaptic nicotinic acetylcholine receptors (α-bungarotoxin receptors) may be widely located on the neuronal membrane as well as on the plasma membrane of satellite and Schwann cells. The physiological significance of this molecular architecture is discussed.     

Administration of 15-methyl-prostaglandin F2α as a pre-operative means of cervical dilatation

Pre-operative dilatation of the cervix prior to vacuum aspiration was accomplished in 67 volunteers by extra-amniotic or intra-muscular administration of 15(S)-15-methyl-PGF_2α (15-me-PGF_2α). Ninety-four per cent of the patients were in the 11th–13th week of gestation and 61% were nulliparae. A single extra-amniotic instillation (mean of 400 μg) or 3 intramuscular injections (300–800 μg per injection) of the compound induced a satisfactory outcome in terms of either abortion or sufficient dilatation of the cervix in 81% of the patients. In the remaining cases, the cervix was found at operation to be open for 7–9 mm which simplified the process of additional instrumental dilatation. In general the outcome of the trial turned the operation into an easy and safe procedure. Vacuum aspiration was performed in all cases after a mean time lag of 16 hours following the onset of the treatment. Extra-amniotic administration was associated with a low incidence of gastro-intestinal side-effects, but there was a transient and moderate degree of uterine pain reaction. The intramuscular route was technically more simple and caused less uterine pain but the high incidence of vomiting and diarrhoea constituted a clinical disadvantage. In late first trimester abortions, particularly cases where the uterus appears larger than expected, it is believed that dilatation of the cervix by PG prior to vacuum aspiration is a sound clinical indication. The method offers definite advantages that compensate for the price of some minor side-effects.     

Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries?

Background: To determine human papillomavirus (HPV) types by polymerase chain reaction (PCR)-reverse line blot assay and examine the concordance between HPV by Hybrid Capture 2 (HC2) and PCR on self-collected vaginal and physician-collected cervical samples and cytology. Methods: This was a cross-sectional study of 546 sexually active women aged ≥30 years with persistent vaginal discharge, intermenstrual or postcoital bleeding or an unhealthy cervix. Participants self-collected vaginal samples (HPV-S) and physicians collected cervical samples for conventional Pap smear and HPV DNA (HPV-P) testing and performed colposcopy, with directed biopsy, if indicated. HPV testing and genotyping was done by HC2 and PCR reverse line blot assay. Concordance between HC2 and PCR results of self- and physician-collected samples was determined using a Kappa statistic (κ) and Chi-square test. Results: Complete data were available for 512 sets with 98% of women providing a satisfactory self-sample. PCR detected oncogenic HPV in 12.3% of self- and 13.0% of physician-collected samples. Overall, there was 93.8% agreement between physician-collected and self-samples (κ = 76.31%, 95% confidence interval [CI]: 64.97–82.29%, p = 0.04)—complete concordance in 473 cases (57 positive, 416 negative), partial concordance in seven pairs and discordance in 32 pairs. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-sampling for detection of cervical intraepithelial neoplasia (CIN)2+ disease were 82.5%, 93.6%, 52.4% and 98.4%, respectively; for physician-sampling they were 87.5%, 93.2%, 52.2% and 98.9%, respectively; and for cytology they were 77.5%, 87.3%, 34.1% and 97.9%, respectively. Concordance between HC2 and PCR was 90.9% for self-samples (κ = 63.7%, 95% CI: 55.2–72.2%) and 95.3% for physician-collected samples (κ = 80.4%, 95% CI: 71.8–89.0%). Conclusions: Self-HPV sampling compares favourably with physician-sampling and cytology. A rapid, affordable, HPV self-test kit can be used as the primary method of cervical cancer screening in low-resource situations.     

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology

A. Talaat, D. Brinkmann, J. Dhundee, Y. Hana, J. Bevan, R. Irvine, S. Bailey and R. Woolas
Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology Objective: To review the risk of pre‐invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. Methods: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary’s Hospital Sidcup. The category of ‘borderline nuclear change in endocervical cells’, result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. Results: A total of 200 women were identified using the hospitals’ pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre‐invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty‐four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. Conclusion: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.     

Will vaccinated women attend cervical screening? A population based survey of human papillomavirus vaccination and cervical screening among young women in Victoria,Australia

Objectives: To assess human papillomavirus (HPV) vaccination coverage and attitudes to vaccination and Pap screening in young women. Design: Population-based telephone survey. Setting: Victoria, Australia. Participants: 234 women resident in Victoria aged 18–28 years in May 2009. Main outcome measures: Self-reported HPV vaccination uptake, reasons for non-receipt or failure to complete vaccination, knowledge and attitudes about HPV vaccination and Pap screening, and cervical screening intentions. Results: The response rate for eligible households was 62.4%. Half of the women (56%, n = 131) had previously had a Pap test and 74% (age standardised estimate) had received HPV vaccine. Of the vaccinated women, 5% had received one dose only, 18% two doses and 76% had completed the course (1.7% unsure of number of doses). Vaccination uptake was highest in the youngest women (declining from 90% for at least one dose in women aged 18–38.5% in women aged 28; p for trend <0.001). Among women who had heard of the vaccine, 96% knew Pap tests were still needed after it, although 20% thought the vaccine could prevent all cervical cancers and 9% thought the vaccine could treat cervical abnormalities and cancer. Among vaccinated women, 8% of women agreed that having been vaccinated made them less likely to have Pap tests in the future. Conclusions: Self-reported coverage in this sample was higher than that recorded on the national vaccination register. Young women report the message that Pap tests are required after vaccination, but there are gaps in their knowledge about the limitations of the vaccine so it remains to be seen if they actually follow through with having Pap tests. Ongoing monitoring of cervical screening rates will be important as this cohort ages.     

Effects of 17β-estradiol on the distribution and activity of some oxydative enzymes of uterine and cervical epithelium in neonatal mice

Summary The following enzymes were studied histochemically in uterine and cervical epithelium from neonatal mice treated with 17-estradiol for the first four days after birth: NADH-, NADPH-, succinate-, -glycerophosphate-, lactate-, glucose-6-phosphate-, and 17-OH-steroid dehydrogenases.It was demonstrated that estradiol administration had a marked influence on distribution and activity of several of the enzymes compared with the control animals. In cervix there was an increase of activity for most of the enzymes, especially in the apical parts of the epithelium cells. The uterine epithelium was also estradiol sensitive as regards most enzymes, and in the case of glucose-6-phosphate dehydrogenase there was a dramatic enhancement of reaction in the uterus of the experimental animals. The differences obtained between cervical and uterine epithelium are described.17-OH-steroid dehydrogenase could not be detected histochemically in the present material.Supported by the Norwegian Research Council for Science and the Humanities.     

Repeat cervical cytology at the time of colposcopy. Is there an added benefit?

OBJECTIVE: To determine if repeating the Pap smear (PS) at colposcopy offers added benefit in the detection of cervical squamous intraepithelial lesions (SILs). STUDY DESIGN: Eight hundred fifty-two women were subjects of this study. Patients with cervical SIL were defined as women with SIL on the repeat PS, or SIL on the colposcopic cervical biopsy (bx) or a negative repeat PS and bx but confirmed SIL on both the previous and follow-up PS or bx. The sensitivities of repeat PS and bx in detecting SIL were calculated. The chi 2 test was used to assess statistical significance. The total cost of repeating the PS was calculated by multiplying the total number of patients (852) by the estimated cost of a single PS ($25). RESULTS: The sensitivities of repeat PS, bx and PS/bx combined were .89, .69 and .92 for low grade SIL (LSIL) and .74, .77 and .98 for high grade SIL (HSIL), respectively (P < .0001). Sixteen percent of the HSIL and 28% of the LSIL cases were diagnosed on repeat PS only (negative bx). If repeat PS was omitted, $21,300 would have been saved.     

The advantages of incorporating liquid-based cytology (TACAS™) in mass screening for cervical cancer

We incorporated liquid-based cytology (LBC) in population-based screening for cervical cancer. The usefulness of using LBC in mass screening for cervical cancer was examined. From 2009 to 2014, 157,061 individuals underwent mass screening for cervical cancer in Aomori Prefecture. From 2009 to 2011, cells were collected from 82,218 individuals and the specimens were conventionally prepared (CP). From 2012 to 2014, cells were collected from 74,843 individuals and the specimens were prepared using LBC (TACAS?). Cytology results for the 2 sets of specimens were compared and differences in cytologic features were examined. ASC-US and more severe lesions were detected at a rate of 1.13 % by CP and 1.44 % by LBC, so LBC had a 1.3-fold higher rate of detection. LBC had a 1.6-fold higher rate of LSIL detection and a 1.2-fold higher rate of HSIL detection. CP detected cancer in 20 cases at a rate of 0.024 % while LBC detected cancer in 18 cases at a rate of 0.024 %. Cytodiagnosis of the 18 cases of SCC that LBC identified revealed that 7 were SCC, 8 were HSIL, and 3 were ASC-H. Atypical cells tended to be smaller with TACAS?. LBC reduced the time needed for microscopic examination of a single specimen by 42 % in comparison to CP. LBC using TACAS? allowed the detection of slight lesions and slight changes in cells. LBC can lessen the burden on medical personnel and may lead to improved accuracy.     

Some properties of adenosine 3′,5′-cyclic monophosphate phosphodiesterase in the superior cervical ganglion of the guinea pig

Adenosine 3,5-cyclic monophosphate (cAMP) phosphodiesterase activity in crude guinea-pig superior cervical ganglion homogenates was assayed under a variety of experimental conditions. Two forms of cAMP phosphodiesterase were found, one with high and the other with low affinity for the substrate. TheK _m values were about 1 and 110 M respectively. Imidazole slightly but constantly stimulated the former enzyme form over a wide range of concentrations and l-methyl-3-isobutylxanthine was a weak competitive inhibitor with aK _i value of 90 M. Low affinity cAMP phosphodiesterase activity was increased by calmodulin and Ca²⁺. This stimulation was not observed in the presence of trifluoperazine, a specific inhibitor of calmodulin. On the other hand, neither [d-Ala²]met-enkephalinamide nor prostaglandin E₂, alone or in combination, influenced high affinity cAMP phosphodiesterase.     

Hyperthermia in cervical cancer – current status

BackgroundThis article reviews the salient features of recent results of clinical studies. It puts a special emphasis on technical aspects, mechanisms of action together with radiotherapy and chemotherapy and points out areas for additional investigation.AimTo present the current state of knowledge on hyperthermia (HT) and to highlight its role in the treatment of cervical cancer.Materials and methodsThe literature on the clinical use of combined hyperthermia for cervical cancer was analyzed. Clinical outcomes together with the technical aspects and the role of HT were also evaluated.ResultsClinically randomized trials have demonstrated benefit including survival with the addition of hyperthermia to radiation or chemotherapy in the treatment of cervical cancer without significant acute or late morbidities. The technological advances have led to an effective and safer treatment delivery, thermal treatment planning, thermal dose monitoring and online adaptive temperature modulation.ConclusionsDue to rapid development over the last decade of hyperthermia systems and new studies at the basic science and clinical level, the perception of hyperthermia as a part of multimodality treatment in cervical cancer has been changed. However, there is still a need for multicentre randomized clinical trials.     

Secular trends of HPV genotypes in invasive cervical cancer in Cali,Colombia 1950–1999

Aim To estimate relative contribution and time trends of HPV types in cervical cancer in Cali, Colombia over a 50 years’ period.MethodsParaffin blocks of 736 cervical cancer histological confirmed cases were retrieved from the pathology laboratory at Hospital Universitario del Valle (Cali, Colombia) and HPV genotyped using SPF10-PCR/DEIA/LiPA25 (version 1) assay. Marginal effect of age and year of diagnosis in secular trends of HPV type prevalence among HPV+ cases were assessed by robust Poisson regression analysis.Results64.7% (95%CI: 59.9–69.2) of squamous cell carcinomas (SCCs) were attributed to HPV 16 and 18, 78.2% (95%CI: 74–82) to HPV 16, 18, 31, 33 and 45 and 84.8% (95%CI: 81–88.1) to HPV 16, 18, 31, 33, 45, 52 and 58 while ninety-three percent of adenocarcinomas (ADCs) were attributed to HPV 16, 18 and 45 only. The prevalence of specific HPV types did not change over the 50-year period. A significant downward trend of prevalence ratios of HPV16 (​P = 0.017) and α7 but HPV 18 (i.e., HPV 39, 45, 68, 70, ​P = 0.024) with increasing age at diagnosis was observed. In contrast, the prevalence ratio to other HPV genotypes of α9 but HPV 16 genotypes (i.e., HPV 31, 33, 35, 52, 58, 67, ​P = 0.002) increased with increasing age at diagnosis.ConclusionNo changes were observed in the relative contribution of HPV types in cervical cancer in Cali, Colombia during the 50 years. In this population, an HPV vaccine including the HPV 16, 18, 31, 33, 45, 52 and 58 genotypes may have the potential to prevent ∼85% and 93% of SCC and ADC cases respectively.     

A multi-body model for comparative study of cervical traction simulation – development,improvement and validation

A computer simulation model was developed to study the dynamic behavior of the cervical spine during cervical traction therapy in inclined and sitting traction positions. The model improved upon an old model with additional components to represent the behavior of the intervertebral discs and the posterior ligaments. The simulation result of the new model was compared against the cervical traction data from a radiographic experiment in both positions. The simulation results of the old model and new model were compared to illustrate the improvement. Using the new model, we compared the timing response of cervical traction in the inclined and sitting positions.