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Cervical Intraepithelial Neoplasia (cervical + intraepithelial_neoplasia)
Kinds of Cervical Intraepithelial Neoplasia Selected AbstractsThe frequency of significant pathology in women attending a general gynaecological service for postcoital bleedingBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 1 2001Adam N. Rosenthal Objectives To document the frequency of pathology in women who complain of postcoital bleeding. To determine whether negative cervical cytology excludes serious pathology in women with postcoital bleeding. To determine whether postcoital bleeding increases the risk of serious pathology in women with an abnormal smear. Design A retrospective study. Setting A university teaching hospital. Population 314 women with postcoital bleeding seen in the gynaecology service from first January 1988 to 31 December 1994. Methods Women were identified from the computerised records of the colposcopy service and copies of correspondence, which was routinely retained on computer. The latter was searched for the text strings coital and intercourse. Main outcome measure Histopathological diagnosis. Results Twelve women (4%) had invasive cancer: 10 were cervical or vaginal cancers and two endometrial cancers. Eight of the 10 cervical or vaginal cancers were clinically apparent. Four women of these 10 had had a normal smear before being referred for further investigation of postcoital bleeding. Two of these cancers were visible only with the aid of the colposcope. Thus, 0.6% of women attending a gynaecology service with postcoital bleeding, a normal looking cervix and a normal smear had invasive cancer of the cervix. Cervical intraepithelial neoplasia were found in 54 women (17.%) and 15 women (5%) had cervical polyps. Nineteen of the 63 women (30%) with significant pathology had a normal or inflammatory cervical smear. No explanation for the postcoital bleeding was found in 155 women (49 %). Conclusions Although invasive cancer is rare in women with postcoital bleeding, it is much commoner than in the general population. It seems likely that cervical intraepithelial neoplasia is also associated with postcoital bleeding, perhaps because the fragile cervical epithelium becomes detached during intercourse. Postcoital bleeding should continue to be regarded as an indication of high risk for invasive cervical cancer and for cervical intraepithelial neoplasia. Prompt referral to a colposcopy clinic is indicated, but most women with postcoital bleeding will have no serious abnormality. [source] The treatment of CIN: what are the risks?CYTOPATHOLOGY, Issue 3 2009W. Prendiville The treatment of squamous cervical intraepithelial neoplasia is to remove or destroy the transformation zone (TZ). It is likely that no method of treatment is superior to another if it is performed properly and the limited available evidence supports this view. The significant advantages of excision (simplicity, cost, outpatient procedure, histological examination of the entire TZ) mean that treatment thresholds may have lowered over the last decade. Long-term pregnancy-related morbidity associated with excision has been reported recently. The evidence would suggest that this increase equates to a genuine increase in serious adverse outcome for cone biopsy but not large loop excision of the transformation zone (LLETZ). The available data also point to an increase in both incomplete excision and premature labour associated with the excision of large endocervical TZs. The clinical implications arising from this are firstly that women with large type 2 and 3 TZs need appropriate counselling before treatment and that the threshold for treating young women with mild abnormalities needs review. [source] Trials update in walesCYTOPATHOLOGY, Issue 2007A. Fiander Three ongoing studies will be presented and discussed. Prevalence of Human Papillomavirus Infection in a South Wales Screening population Methods: A total of 10 000 consecutive, anonymous liquid based cytology screening samples were collected over a five month period in 2004. Age, cytology result and social deprivation score was provided for each specimen. The methodology was chosen to ensure inclusion of all women attending routine cervical screening, avoiding potential constraints associated with obtaining individual informed consent. The liquid based cytology samples were processed and reported by the receiving cytology laboratory and the residual specimens sent to the HPV Research Laboratory, Wales College of Medicine, where they were processed and stored at -80°C until analysis. High risk and low risk HPV Typing was undertaken using PCR , EIA (Jacobs et al 1997). Full high risk typing was performed on HPV positive specimens. Results: The study population had a mean age of 38 years with 92% negative, 5% borderline and 3% dyskaryotic cytology. The average social deprivation score was 17.4 (based upon the Welsh Index of multiple deprivation). The following results will be presented: HPV prevalence by age. HPV prevalence by cytology result. Type specific HPV prevalence in single and multiple infection. Conclusion: This study represents the largest type specific HPV Prevalence Study in the UK to date. As such it will form a useful base line against which to access performance of marketed HPV tests and evaluating the impact following implementation of HPV vaccination. [Funded by Welsh Office for Research and Development] CRISP , 1 Study (Cervical Randomized Intervention Study Protocol -1) Background: Indole-3-carbinol (I3C) and Diindolylmethane (DIM) are found in cruciferous vegetables and have been identified as compounds that could potentially prevent or halt carcinogenesis. I3C spontaneously forms DIM in vivo during acid digestion. I3C has been shown to prevent the development of cervical cancer in HPV 16 transgenic mice and both I3C and DIM have been shown to promote cell death in cervical cancer cell models. DIM is the major active bi-product of I3C and preliminary data indicate that DIM is active in cervical dysplasia and may be better tolerated than I3C. Aim: To investigate chemoprevention of high grade cervical neoplasia using Diindolylmethane (DIM) supplementation in women with low grade cytological abnormalities on cervical cytology. Objectives: To observe any reduction in the prevalence of histological proven high-grade cervical intraepithelial neoplasia (CIN) after 6 months of supplementation. ,,To observe any reduction in the prevalence of cytological abnormalities. ,,To observe any changes in the clinical appearance of the cervix. To assess acceptability and monitor any side effects of DIM supplementation. ,,To assess whether any benefit is seen in relation to Human Papillomavirus (HPV) status including HPV Type, Viral load and integration. Methods: This is a double blind randomized placebo-controlled trial involving 600,700 women with low grade cytological abnormalities on a cervical smear. Randomization is in the ratio of 2 : 1 in favour of active medication. Women with first mildly dyskaryotic smear or second borderline smear are eligible. They are asked to take two capsules daily for 6 months. At the end of 6 months they undergo repeat cervical cytology, HPV testing and colposcopy. Results: A progress report will be given for this ongoing study. [Funded: - Cancer Research UK] Type Specific HPV Infection in Welsh Cervical Cancers Background: Whilst there have been numerous studies of HPV infection associated with cervical cancer and on prevalence of Human Papillomavirus in diverse populations there have been no studies of these variables in the same population. Against a background of prophylactic HPV vaccination it is important to assess potential protection against cervical cancer within a given population. The most comprehensive analysis of HPV type specific cervical cancer is a meta-analysis published by the IARC in 2003. This however included only three UK based studies, totalling 118 cases, 75 of which were only investigated by HPV type PCR for four high risk types. None of this data was presented with associated population based prevalence data. Therefore, the research objectives for this study in combination with the first study above, are as follows: To determine the frequency of specific HPV types in cervical cancers in Wales. To compare the distribution of specific HPV types amongst cervical cancers with their prevalence in the general population. This will allow accurate delineation of the relationship between prevalence of specific HPV types in the general population and their association with clinically relevant disease. This information is a pre-requisite to assess the potential impact of prophylactic vaccination against HPV infection in Wales. Methods: Welsh Cervical Cancer specimens from 2000,2005 will be identified from pathology departments within Wales. The pathology of each tumour will be reviewed by a single Gynaecological Pathologist. The age of the patient and pathological features of the tumour will be noted. DNA will be extracted from the paraffin sections and HPV typed by PCR-EIA. Results: A progress report will be given for this ongoing study. [Funded by Welsh Office for Research and Development] [source] Borderline nuclear change; can a subgroup be identified which is suspicious of high-grade cervical intraepithelial neoplasia, i.e. CIN 2 or worse?CYTOPATHOLOGY, Issue 5 2002J. M. Edwards Borderline nuclear change; can a subgroup be identified which is suspicious of high-grade cervical intraepithelial neoplasia, i.e. CIN 2 or worse? Only 10% of first borderline smears are associated with a histological high-grade (HG) abnormality, i.e. CIN 2,3, invasive malignancy or glandular neoplasia on subsequent investigation. The advantages of highlighting this subgroup are obvious but is this possible? From 1996 and 1997, 242 borderline smears with histological follow-up were examined by two independent experienced observers (observer 1 and 2) without prior knowledge of further investigation results. For each smear a profile of nuclear details was produced, also noting the type of cell mainly affected by the process; then the observers were asked to assess the degree of worry of HG disease for each smear i.e. whether the smear fell into group 1 borderline changes indicative of low-grade (normal, inflammatory, CIN1/HPV) disease (BL/LG) or group 2 difficult borderline smear, HG disease (CIN 2,3, invasive neoplasia or glandular neoplasia) cannot be excluded (BL/HG). Observer 1 selected a group of BL/HG with a PPV for HG disease of 38%, with observer 2 having a PPV of 50%; this compared with the overall laboratory HG disease PPV for borderline smears of 14%. Both observers found the most useful criterion to be the increase in nuclear:cytoplasmic ratio. Our results show that it is possible to separate a small group of borderline smears which should be classified as ,borderline/high grade lesion difficult to exclude' (BL/HG). Both observers had some success in arriving at this classification although their method of selecting out this group was quite different. [source] CK17 and p16 expression patterns distinguish (atypical) immature squamous metaplasia from high-grade cervical intraepithelial neoplasia (CIN III)HISTOPATHOLOGY, Issue 5 2007S Regauer Aims:, Atypical immature metaplasia (AIM) refers to a full-thickness intraepithelial basaloid lesion in the uterine cervix that features both metaplasia and atypia and is therefore difficult to distinguish from high-grade cervical intraepithelial neoplasia (CIN III). p16 is a marker for human papillomavirus (HPV)-induced dysplasia. Cytokeratin (CK) 17 is a marker for cervical reserve (stem) cells, which give rise to metaplasia. The aim was to determine whether AIM can be reclassified into metaplasia and CIN III based on p16 and CK17 immunohistochemistry. Material and results:, Seventy-five cervical biopsy specimens, curettings and cone excisions containing varying proportions of dysplasia and metaplasia and 20 cases regarded as AIM were analysed immunohistochemically with antibodies to CK17, p16 and p63. In immature metaplasia all proliferating cells were immunoreactive with antibodies to CK17 and p63, while p16 was negative. All dysplastic cells of CIN III demonstrated uniform immunoreactivity for p16 and p63, but were CK17,. Based on the reciprocal immunoreactivity of p16 and CK17, 17/20 cases of AIM were reclassified as metaplasia (n = 10) and CIN III (n = 7). Three cases of AIM stained for both CK17 and p16 and were classified as CIN III. Conclusion:, ,AIM' is a helpful histological descriptor but it should not be used as a final diagnosis. Immunohistochemistry for p16 and CK17 allows distinction between metaplasia and high-grade CIN. [source] The health and economic effects of HPV DNA screening in The Netherlands,INTERNATIONAL JOURNAL OF CANCER, Issue 9 2010Johannes Berkhof Abstract We studied the health and economic effects of human papillomavirus (HPV) DNA testing in cervical screening using a simulation model. The key data source was a Dutch longitudinal screening trial. We compared cytological testing with repeat cytology (for borderline/mildly abnormal smears) to HPV testing with cytology triage (for HPV-positive smears), combination testing (combined HPV and cytology) and cytological testing with HPV triage (for borderline/mildly abnormal smears). We varied the screening interval from 5 to 10 years. The main outcome measures were the number of cervical cancer cases, the number of quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The base-case estimates were accompanied with ranges across 118 calibrated parameter settings (calibration criteria: cervical intraepithelial neoplasia 2/3, cancer and mortality rates). In comparison to 5-yearly cytology, 5-yearly HPV testing with cytology triage gave a reduction in the number of cancer cases of 23% (range, 9,27%). The reduction was 26% (range, 10,29%) for combination testing and 3% (range, ,1 to 8%) for cytology with HPV triage. For strategies with primary HPV testing, the model also estimated a reduction in cancer cases when the screening interval was extended to 7.5 years. Five-yearly cytology with HPV triage and 5 to 7.5-yearly HPV testing with cytology triage were cost effective for the base-case settings and the majority of calibrated parameter settings (ICER below Dutch willingness-to-pay threshold of ,20,000/QALY). Our model indicates that HPV testing with cytology triage is likely to be cost effective. An extension of the screening interval may be considered to control costs. [source] Incidence and outcome of acquisition of human papillomavirus infection in women with normal cytology,A population-based cohort study from TaiwanINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Angel Chao Abstract Little is known about acquisition of human papillomavirus (HPV) and its outcome among older women with negative HPV testing and normal cytology. A longitudinal 3-yr follow-up of nested-cohort subjects (n = 8825) from a population-based cervical cancer screening study whose Pap and HPV tests were negative at baseline were conducted. Every active HPV-negative (n = 413) participant had 12-mo follow-ups of Pap smear and HPV testing. Colposcopy was performed if either HPV-positive or cytology was abnormal. The cytology and histology information of the remaining subjects (passive HPV-negative, n = 8412) was obtained from national registry database. Median age of participants was 45 yr (range, 30,73 yr). The incidence of new acquisition was 4.2/100 woman-years. The 3-yr cumulative total HPV acquisition rate was 11.1% (95% confidence interval [CI]: 8.1,14.1). Increased number of sexual partners (,2 vs. 1) of the participant was associated with risk of acquisition (odds ratio [OR]: 5.0, 95% CI: 2.0,12.6) by multivariate analysis. Three cases of , cervical intraepithelial neoplasia (CIN) 2 were identified in 3-yr follow-up in active HPV-negative subjects. HPV genotypes in the dysplastic tissue were actually present at baseline samples after reanalysis. From the passive HPV-negative group, only 1 case progressed to CIN2 probably after HPV acquisition. Negative Pap and HPV tests assured a very low risk of developing , CIN2 within 3 yr despite incident HPV infection. [source] Cervical cancer screening program integrating Pap smear and HPV DNA testing: A population-based studyINTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Angel Chao Abstract We conducted a population-based cohort study to evaluate the complementary value of HPV testing to Papanicolaou (Pap) smear and the prevalence and genotype distribution of HPV in Taiwan. In this report, we described the design of the whole study and analyzed the cross-sectional results. Female residents (age , 30 years) of Taoyuan, Taiwan were invited. After signing informed consent, every participant had a Pap smear and a HPV testing. Patients with Pap , atypical squamous cell of undetermined significance (Group I) or those with HPV-positive but normal cytology (Group II) were referred for a colposcopic examination. A total of 10,014 women were eligible. The overall HPV prevalence was 10.8% (95% confidence interval 10.5%,11.4%) in the study population. A total of 37 types of HPV were identified and the leading three were HPV-52, -18 and -58. There was a significant positive correlation of HPV prevalence with older age, postmenopausal status, current-user of oral contraceptives and never-user of hormone replacement therapy. Past users of oral contraceptives and never users of Pap were associated with higher risk of abnormal Pap, while age 40,49 strata had lower risk. Fifty-nine cases of cervical intraepithelial neoplasia (CIN) 2 from Group I and additional 11 from Group II were identified. The improvement of sensitivity with additional HPV testing was 15.3%. Besides, no specific subgroup was found to most benefit from the combined strategy. The value of adding HPV test to conventional Pap smear has to be evaluated after longer-term follow-up of this population-based cohort. © 2008 Wiley-Liss, Inc. [source] Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3)INTERNATIONAL JOURNAL OF CANCER, Issue 12 2007Andreas M. Kaufmann Abstract Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus-like particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1- and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo-controlled clinical trial has been conducted in 39 HPV16 mono-infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 ,g or 250 ,g) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty-six percent of the responders were also HPV16 DNA-negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine. © 2007 Wiley-Liss, Inc. [source] CD4+CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasiaINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Johan W. Molling Abstract CD4+CD25hiCTLA4+FoxP3+ regulatory T cells (Treg) have been shown to maintain immune tolerance against self antigens and increased circulating frequencies have been reported in various types of cancers. Circulating invariant natural killer T-cells (iNKT) are reduced in cancer patients and low iNKT frequency is related to poor prognosis. It is not yet clear whether high Treg numbers and low iNKT cell numbers pose an increased risk for the progression of premalignant lesions or whether Treg and iNKT cell numbers are influenced by dysplasia. We therefore studied prospectively the relation between iNKT cell and Treg frequencies and the natural course of human papillomavirus type 16 (HPV16) induced pre-malignant cervical dysplasia in 82 patients who participated in a nonintervention cohort study of women with abnormal cytology. Treg frequencies were significantly increased in women who had persistent HPV16 infection. Within the HPV16 persistence group there was no difference in Treg frequencies among patients who developed a CIN3 lesion and patients who did not progress to CIN3. Furthermore, Treg frequencies were increased in patients who had detectable HPV16 E7 specific IL-2 producing T-helper cells, which suggests a causal role of HPV infection in Treg development in parallel with HPV16 specific T helper cells. No evidence was found for a role for iNKT cells in persistence of HPV16 and progression of HPV16 induced CIN lesions. However, HPV-persistence-associated Tregs may explain the inefficacy of concomitant persistence associated immunity and may contribute to subsequent progression to neoplasia. © 2007 Wiley-Liss, Inc. [source] Cross-sectional analysis of oncogenic HPV viral load and cervical intraepithelial neoplasiaINTERNATIONAL JOURNAL OF CANCER, Issue 5 2006Roberto Flores Abstract In human papillomavirus (HPV)-associated carcinogenesis, HPV infection characteristics such as viral load may play an important role in lesion development. The purpose of this study was to determine the association between quantitative assessment of oncogenic HPV viral load, and abnormal cytology among women residing along the United States,Mexico border. A cross-sectional study of 2,319 women was conducted between 1997 and 1998. Viral load of oncogenic HPV types (16, 18, 31, 39, 45, 51, 52, and 58) was measured among 173 HPV (+) women using quantitative real-time PCR. Overall, HPV 16, 31, 52 and 58 showed the highest viral load. Single type infection had higher viral loads compared to multiple type infections. HPV viral load declined significantly (p = 0.04) with age. No significant association was observed with other known HPV risk factors such as oral contraceptive use, parity, sexual and STD history. Viral load was independently associated with degree of cervical lesions. An adjusted odds ratio (AOR) of 4.7 for the association between increasing total viral load and Atypical Squamous Cells of Undetermined Significance (ASCUS)/Atypical Glandular Cells of Undetermined Significance (AGUS) was observed (p for trend <0.01). Increased risk of low-grade SIL was observed with higher viral load compared with HPV negative women (AOR = 47.7 for total viral load; AOR = 37.1 for HPV viral load not including HPV16, and AOR = 25.9 for HPV16 viral load). Likewise, increased risk of high-grade SIL with higher viral loads was observed (AOR = 58.4 for high total viral load compared with HPV negative women, AOR = 58.1 for HPV viral load not including HPV16, and AOR = 69.8 for HPV16 high viral load). Results from this study suggest a dose,response relationship between increasing oncogenic HPV viral load and risk of LSIL and HSIL. © 2005 Wiley-Liss, Inc. [source] The role of genotype-specific human papillomavirus detection in diagnosing residual cervical intraepithelial neoplasiaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2002Ruud LM Bekkers Abstract We assessed prospectively whether residual cervical intraepithelial neoplasia (CIN) after treatment for high-grade CIN can be predicted by genotype-specific high-risk HPV (HR-HPV) detection in follow-up cervical scrapes. A broad spectrum, highly sensitive SPF10 -LiPA-PCR HPV detection technique was used on cervical scrapes before large loop excision of the transformation zone (LLETZ), on the LLETZ biopsy and on follow-up scrapes of 90 patients treated for high-grade CIN. HR-HPV was detected in the biopsies of 93% (n = 84) of the patients and in the follow-up scrapes of 48% (n = 43) of the patients. In 12 patients, genotype-specific HR-HPV persistence was detected in both follow-up scrapes. In 10 patients, residual CIN was detected. In 5 of these patients (including all patients with residual CIN 3), the follow-up scrapes showed genotype-specific HR-HPV persistence. In 2 patients, a different HR-HPV was detected, and 3 patients had HR-HPV-negative follow-up scrapes. Conventional cytologic follow-up was abnormal in 13 patients including all 10 patients with residual CIN. The negative predictive value (NPV) of HR-HPV detection on follow-up scrapes was high (94%). Repeat detection of genotype-specific HR-HPV showed a lower sensitivity and NPV than repeat detection of any HR-HPV, but its specificity was higher. Repeat conventional cytologic follow-up showed the highest sensitivity and NPV. In conclusion, the presence of HR-HPV in cervical scrapes after LLETZ for high-grade CIN is a risk factor for the presence of residual CIN. HR-HPV genotype-specific persistence is specifically present in patients with residual CIN 3. However, HR-HPV detection cannot predict or exclude the presence of residual CIN in the individual patient and additional procedures remain necessary. © 2002 Wiley-Liss, Inc. [source] 1H magnetic resonance spectroscopy of preinvasive and invasive cervical cancer: In vivo,ex vivo profiles and effect of tumor loadJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2004Marrita M. Mahon PhD Abstract Purpose To compare in vivo 1H magnetic resonance (MR) spectra of preinvasive and invasive cervical lesions with ex vivo magic angle spinning (MAS) spectra of intact biopsies from the same subjects and to establish the effects of tumor load in the tissue sampled on the findings. Materials and Methods A total of 51 subjects (nine with normal cervix, 10 with cervical intraepithelial neoplasia [CIN], and 32 with cervical cancer) underwent endovaginal MR at 1.5 T. Single-voxel (3.4 cm3) 1H MR spectra were acquired and voxel tumor load was calculated (tumor volume within voxel as a percentage of voxel volume). Resonances from triglycerides ,CH2 and ,CH3 and choline-containing compounds (Cho) were correlated with voxel tumor load. Biopsies analyzed by 1H MAS-MR spectroscopy (MRS) had metabolite levels correlated with tumor load in the sample at histology. Results In vivo studies detected Cho in normal, CIN, and cancer patients with no significant differences in levels (P = 0.93); levels were independent of voxel tumor load. Triglyceride ,CH2 and ,CH3 signals in-phase with Cho were present in 77% and 29%, respectively, of cancer subjects (but not in normal women or those with CIN), but did not correlate with voxel tumor load. Ex vivo cancer biopsies showed levels of triglycerides ,CH2 and ,CH3 and of Cho that were significantly greater than in normal or CIN biopsies (P < 0.05); levels were independent of the tumor load in the sample. The presence of ,CH2 in vivo predicted the presence of cancer with a sensitivity and specificity of 77.4% and 93.8% respectively, positive (PPV) and negative (NPV) predictive values were 96% and 68.2%; for ,CH2 ex vivo, sensitivity was 100%; specificity, 69%; PPV, 82%; and NPV, 100%. Conclusion Elevated lipid levels are detected by MRS in vivo and ex vivo in cervical cancer and are independent of tumor load in the volume of tissue sampled. J. Magn. Reson. Imaging 2004;19:356,364. © 2004 Wiley-Liss, Inc. [source] Cervical and oral human papillomavirus types in HIV-1 positive and negative women with cervical disease in South AfricaJOURNAL OF MEDICAL VIROLOGY, Issue 6 2008Dianne J. Marais Abstract This study tested cervical and oral human papillomavirus (HPV) infection in HIV-1 seropositive (HIV+) and seronegative (HIV,) women to determine any association between infections at both sites and the difference in prevalence of the HPV types infecting these women. Participants were 115 women referred to a colposcopy clinic after diagnosis of abnormal cervical cytology. The women showed low grade cervical intraepithelial neoplasia (CIN1) or high grade disease (CIN2/3) or no CIN based on colposcopy and histology. Typing of HPV in cervical and oral cells was by Roche linear array and included direct sequencing on selected oral samples. Cervical HPV prevalence was 86.5% and 97.1% in HIV, and HIV+ women respectively. With the exception of HPV-45, prominent in HIV+ women, the hierarchy of predominant types were similar in HIV, and HIV+ women. HPV-16 was most prevalent in both HIV+ (41.7%) and HIV, women (38.5%) with CIN2/3. Significantly more HIV+ women had multiple cervical (>1) infections than HIV, women (36.1% vs. 88.2%, P,<,0.001) and more oral HPV infections (45.5% and 25% respectively; P,=,0.04). The most prevalent oral HPV types were HPV-33, -11, and -72. The majority of women did not have concordant oral and cervical HPV types, reflecting possible independence of infection at the two sites. HIV immune suppression did not impact significantly on the predominant types of cervical HPV infection (except for HPV-45). HIV+ women had more multiple HPV infections and those with severe cervical disease a similar prevalence of HIV-16 but a lower HPV-18 prevalence than HIV, women. J. Med. Virol. 80:953,959, 2008. © 2008 Wiley-Liss, Inc. [source] Molecular variants of human papillomavirus type 16 and 18 and risk for cervical Neoplasia in PortugalJOURNAL OF MEDICAL VIROLOGY, Issue 12 2007Angela Pista Abstract Persistent high-risk human papillomavirus (HPV) infection is considered as the central cause of invasive cervical cancer. Specific HPV 16 and 18 sequence variations were associated with an increased risk for progression. The purpose of this study was to analyze intratypic variations of HPV 16 and 18 within the E6 gene, MY09/11 and LCR regions, and to evaluate the risk of these variants for cervical neoplasia among Portuguese women. Cervical samples from 187 HPV 16-positive and 41 HPV 18-positive women with normal epithelium, cervical intraepithelial neoplasia, or invasive cervical cancer were amplified by type-specific PCR, followed by sequence and phylogenetic analysis. Sixteen new HPV 16 and 18 patterns are described in this paper. European HPV 16 variants were the most frequent (74.3%), particularly Ep-T350 (44.4%), followed by African (16.1%), and Asian-American (9.6%). Non-European HPV 16 variants were more frequent in pre-invasive lesions than in normal tissue and low-grade lesions. However, when analyzed separately, only African variants were associated significantly with an increased risk for cervical cancer. For HPV 18, the AsAi variant showed a trend, which was not statistically significant to an enhanced oncogenicity. European variants seemed to be significantly associated with a lower risk for cervical cancer development. The distribution of HPV 16 and 18 variants was not related to age or race among women living in the same geographical region. Knowledge of variants will be important for risk determination as well as for designing primers or probes for HPV detection methods, and for appropriate cervical cancer prevention strategies. J. Med. Virol. 79:1889,1897, 2007. © Wiley-Liss, Inc. [source] Variation in human papillomavirus type-16 viral load within different histological grades of cervical neoplasiaJOURNAL OF MEDICAL VIROLOGY, Issue 9 2007A.N. Fiander Abstract The objective of this study was to investigate variation in human papillomavirus (HPV) type-16 load within histologically defined grades of cervical intraepithelial neoplasia. Two hundred and thirty-seven liquid based cytology samples were collected from women attending colposcopy clinics, DNA was extracted, and presence of virus determined by PCR-enzyme immunoassay. Quantitative real-time PCR was used to determine viral load for 70 HPV-16 positive single infections. Viral load was expressed as the ratio of copies of the viral L1 gene to copies of the human beta-globin gene. Measurements varied from 0.019 to 4,194 HPV genomes per cell. Our data demonstrate that in cervical neoplasia, HPV load tends to correlate with disease severity, but that the number of viral genomes/cell varies considerably within histological grades. This variation within disease grades currently limits the clinical utility of viral load measurement. [source] High-risk HPV presence in cervical specimens after a large loop excision of the cervical transformation zone: Significance of newly detected hr-HPV genotypesJOURNAL OF MEDICAL VIROLOGY, Issue 3 2007Maaike A.P.C. van Ham Abstract Large loop excision of the cervical transformation zone (LLETZ) is a well-established treatment for high-grade cervical intraepithelial neoplasia. It has even been postulated that LLETZ is responsible for the elimination of the infectious agent, human papillomavirus (HPV), causing the lesion. Most studies on HPV detection after LLETZ have focused on the persistence of high-risk (hr-) HPV to identify women at risk for residual or recurrent disease. Therefore, the appearance and significance of hr-HPV types newly detected after surgical treatment has not been studied extensively so far. The presence of hr-HPV in 85 high-grade squamous cervical LLETZ biopsies and in the first follow-up smear was determined. In 80 (94%) of the LLETZ biopsies hr-HPV was detected in contrast to 30 (35%) hr-HPV positive follow-up scrapes. Twenty of the 80 hr-HPV positive women (25%) had the same hr-HPV genotypes in their follow-up cervical smears as was found in the corresponding biopsies. In the follow-up smear of 13 women a new hr-HPV genotype was detected and HPV 18 was newly detected in 8 of them. The remarkably high presence of newly detected HPV 18 genotypes may argue for a release or re-activation of this virus from proximal layers of the cervical canal incised during surgery. J. Med. Virol. 79:314,319, 2007. © 2007 Wiley-Liss, Inc. [source] Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate,LASERS IN SURGERY AND MEDICINE, Issue 9 2008Philipp Soergel MD Abstract Background and Objective CIN is a disease of women in their reproductive years, and treatment includes excisional techniques with increased risk of preterm deliveries. Photodynamic therapy (PDT) using topical precursor of photoactive porphyrins may be a non-invasive alternative with minimal side effects. This study assessed the feasibility and response rate of PDT with hexaminolevulinate (HAL) in cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection. Study Design/Materials and Methods Twenty four patients with a CIN 2 or 3 or a persistent CIN 1 and a positive high-risk HPV-DNA test were included. Each patient had gynaecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy. Ten milliliters of HAL-thermogel (10 mM) were topically applied to the cervix for 3,5 hours, followed by 1,000 seconds of illumination of both ecto- and endocervical canal with red coherent light (wave length 633 nm) using a PDT laser and a special light catheter. Follow-up examinations were carried out after 3 (cytology, colposcopy, HPV DNA testing, and if needed re-PDT) and 6 months. Results Seven, 10, and 7 patients had a CIN 1, 2, or 3, respectively. Treatment could be accomplished in all cases and no severe side effects were encountered. Fifteen out of the 24 patients had a complete response (15/24,=,63%) and a HPV remission 6 months after 1,3 treatments. The remission rates were 71%, 50%, and 71% for CIN 1, 2 and 3. Conclusion HAL PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects which can be easily performed on outpatient basis. Lesers Surg. Med. 40:611,615, 2008. © 2008 Wiley-Liss, Inc. [source] Investigation of metabolite changes in the transition from pre-invasive to invasive cervical cancer measured using 1H and 31P magic angle spinning MRS of intact tissueNMR IN BIOMEDICINE, Issue 2 2009Sonali S. De Silva Abstract The aim of this study was to determine the metabolic changes in the transition from pre-invasive to invasive cervical cancer using high-resolution magic angle spinning (HR-MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n,=,5), cervical intraepithelial neoplasia (CIN; mild, n,=,5; moderate/severe, n,=,40), and invasive cancer (n,=,23). 1H HR-MAS MRS data were acquired using a Bruker Avance 11.74,T spectrometer (Carr,Purcell,Meiboom,Gill sequence; TR,=,4.8,s; TE,=,135,ms; 512 scans; 41,min acquisition). 31P HR-MAS spectra were obtained from the normal subjects and cancer patients only (as acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a 1H-decoupled pulse-acquire sequence (TR,=,2.82,s; 2048 scans; 96,min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of choline (P,=,0.0001) and phosphocholine (P,=,0.002) in tissue from patients with cancer than from patients with high-grade dyskaryosis, but no differences between non-cancer groups. Division by histology of the sample also showed increases in choline (P,=,0.002) and phosphocholine (P,=,0.002) in cancer compared with high-grade CIN tissue. Phosphoethanolamine was increased in cancer compared with normal tissue (P,=,0.0001). Estimated concentrations of alanine (P,=,0.01) and creatine (P,=,0.008) were significantly reduced in normal tissue from cancer patients compared with normal tissue from non-cancer patients. The estimated concentration of choline was significantly increased in CIN tissue from cancer patients compared with CIN tissue from non-cancer patients (P,=,0.0001). Estimated concentrations of choline-containing metabolites increased from pre-invasive to invasive cervical cancer. Concurrent metabolite depletion occurs in normal tissue adjacent to cancer tissue. Copyright © 2008 John Wiley & Sons, Ltd. [source] Preinvasive and invasive cervical cancer: an ex vivo proton magic angle spinning magnetic resonance spectroscopy studyNMR IN BIOMEDICINE, Issue 3 2004Marrita M. Mahon Abstract The aim of this study was to obtain 1H MR spectra using magic angle spinning (MAS) techniques from punch biopsies (<20,mg) of preinvasive and invasive cervical disease and to correlate the spectral profiles with sample classification on the basis of histopathology. Tissue samples were obtained at colposcopic examination, during local treatment of cervical intraepithelial neoplasia (CIN) or at hysterectomy. 1H MAS MRS was performed at 25°C while spinning the sample at 4.5,kHz. After measurement, the tissue was immersed in formalin and the pathology determined. Histological examination after 1H MAS MRS defined 27 samples with squamous cell carcinoma (SCC), 12 with CIN and 39 with only normal tissue. The standardized integrals of the lipid, choline and creatine regions of the spectra were significantly higher in SCC than in normal or CIN tissue. There was no obvious difference in the standardized integral of the region 4.15,3.5,ppm. The acyl fatty acid side-chain length was longer or less unsaturated in SCC than in normal tissue. Normal tissue from patients with SCC showed significantly higher triglycerides than normal tissue from patients with benign uterine disease but significantly lower triglycerides than SCC tissue. 1H MAS MRS of the uterine cervix ex vivo may be used to differentiate non-invasive from invasive cervical lesions, increase interpretation of in vivo MRS and provide insights into tumor biology. Copyright © 2004 John Wiley & Sons, Ltd. [source] HER2/neu (c-erbB-2) gene amplification and protein expression are rare in uterine cervical neoplasia: a tissue microarray study of 814 archival specimensAPMIS, Issue 10 2009IANA LESNIKOVA Published studies have reported widely variable incidence of HER2/neu (c-erbB-2) protein expression and HER2/neu (c-erbB-2) gene amplification in cervical carcinoma. We examined tissue microarrays (TMAs) constructed from 814 formaldehyde-fixed paraffin-embedded archival specimens of cervical intraepithelial neoplasia (CIN)1 (n = 262), CIN2 (n = 230), CIN3 (n = 186) and invasive carcinoma (n = 136), for HER2/neu protein expression by immunohistochemistry (IHC) and for HER2/neu gene amplification by chromogenic in situ hybridization (CISH). We found moderate or strong immunohistochemical positivity for HER2/neu in 64 of 814 specimens (7.9%). Using CISH, polysomy of the HER2/neu gene was detected in 87 cases (10.7%), low/borderline amplification in five cases (0.6%) and true amplification in four cases (0.5%). The correlation between IHC and CISH was statistically significant in CIN2, CIN3 and invasive cervical carcinoma specimens. When present, Her-2/neu positivity is more commonly seen in higher grades of cervical dysplasia and in carcinoma. However, this large TMA study shows that HER2/neu oncoprotein expression and HER2/neu gene amplification overall are uncommon events in cervical neoplasia. This provides compelling evidence that HER2/neu plays no major role in the development and progression of cervical neoplasia. [source] Original Article: Consequences in women of participating in a study of the natural history of cervical intraepithelial neoplasia 3AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 4 2010Margaret R.E. MCCREDIE Background:, A retrospective cohort study was performed in 1063 women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (previously termed carcinoma in situ, CIS) in the National Women's Hospital, Auckland, New Zealand. The study describes the clinical management and outcomes for women with CIN3 diagnosed in the decade of 1965,1974, when treatment with curative intent was withheld in an unethical clinical study of the natural history of CIS. A comparison is made with women who were diagnosed earlier (1955,1964) and later (1975,1976). Aims:, The aim of the study is to record the medical encounters, frequency and management of cytological abnormalities and the occurrence of invasive cancers. The medical records, cytology and histopathology were reviewed and data linked with cancer and death registers. Results:, Women diagnosed with CIN3 in 1965,1974 (n = 422), compared with those diagnosed earlier (n = 385) or later (n = 256): (i) were less likely to have initial treatment with curative intent (51% vs 95 and 85%, respectively); (ii) had more follow-up biopsies (P < 0.0005); (iii) were more likely to have positive cytology during follow-up (P < 0.005) and positive smears that were not followed within six months by a treatment with curative intent (P < 0.005); and (iv) experienced a higher risk of cancer of the cervix or vaginal vault (RR = 3.3 compared with the first period, 95% CI: 1.7,5.3). Among women diagnosed in 1965,1974, those initially managed by punch or wedge biopsy alone had a cancer risk ten times (95% CI: 3.9,25.7) higher than women initially treated with curative intent. Conclusions:, During the ,clinical study' (1965,1974), women underwent numerous interventions that were aimed to observe rather than treat their condition, and their risk of cancer was substantially increased. [source] Should liquid-based cytology be performed prior to colposcopy?AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2009A comparison of the accuracy, cost in a tertiary referral setting, unsatisfactory rates Objective:, To compare the use of liquid-based cytology (LBC) with conventional cytology (CC) in the assessment cervical intraepithelial neoplasia (CIN) prior to colposcopy. Design:, Retrospective Cohort Study. Methods:, Liquid-based cytology and CC findings were compared with colposcopic assessment and directed cervical biopsy in terms of sensitivity and specificity for high grade lesions only and for any abnormalities. The degree of correlation was sought. Secondary outcomes were unsatisfactory rate and cost. Results:, A total of 1961 women had colposcopy of whom 528 had cervical biopsy. LBC and CC have similar sensitivity and specificity for both high-grade lesions and any abnormalities. In comparison with cervical biopsy, LBC and CC sensitivity for high-grade disease was 89.1% and 88.6% respectively and for any abnormalities, the sensitivity was 86.6% and 87.0%. Specificity for high-grade disease was 83.1% and 84.7% and for any abnormalities, the specificity was 53.8% and 56.4%. The unsatisfactory rate was significantly lower in LBC 4.38% compared to 1.84% (P < 0.001). However, the use of LBC was associated with an additional cost of A$1496 for each unsatisfactory smear avoided. Conclusion:, In high prevalence setting, LBC showed no statistically significant difference in sensitivity and specificity from CC for the detection of CIN. A reduction in unsatisfactory smears was evident, but at significant additional cost. [source] Comparison of three management strategies for patients with atypical squamous cells of undetermined significance, after six months delay: A three-year experience in an Iranian university hospitalAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009Fariba YARANDI Background: A Pap test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5,10% of women with ASCUS harbour serious cervical disease. Methods: We screened 3619 women, who attended to Mirza Koochak Khan Hospital at Tehran University of Medical Sciences with Pap smears, of whom 100 returned with ASCUS. After six months, each subject underwent a standard cytology (conventional Pap smear), human papillomavirus (HPV) DNA testing (identifying high-risk HPV types with polymerase chain reaction) and colposcopy with multiple cervical biopsies. Results: Mean age was 44.09 ± 8.6 years. The estimated prevalence of cervical intraepithelial neoplasia (CIN) II or higher was 4%. When histologically verified high-grade lesions (, CIN II) were observed, the relative sensitivity of HPV DNA testing was 100% compared with conventional Pap smear, which performed 75% versus 100% relative sensitivity, respectively, using cytological diagnosis high-grade squamous intraepithelial lesion, or low-grade squamous intraepithelial lesion (LSIL) as the cut-off. Negative and positive predictive values (NPV and PPV) of Pap test were 98.9% and 100%. The NPV and PPV of HPV DNA testing were 100%. Conclusions: Although less complicated than colposcopy, the repeat Pap smear triage algorithm for ASCUS may underdiagnose some women with high-grade CIN, when compared with colposcopy. Considering the high sensitivity of HPV testing, it may be useful as an alternative to the current policy of six-month repeat cytology for women with ASCUS results. [source] Haemostasis after cold-knife conisation: A randomised prospective trial comparing cerclage suture versus electro-cauterisationAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2008Cem DANE Aims: The purpose of this study was to compare two different techniques of obtaining haemostasis after cold-knife conisation. Methods: Seventy-eight women who required conisation for treatment of cervical intraepithelial neoplasia were prospectively enrolled in a randomised clinical trial to receive either cerclage with cold-knife conisation or cautery with cold-knife conisation. Outcome measures evaluated include estimated blood loss, operative time, early late haemorrhage and dysmenorrhoea. The short- and long-term morbidity was compared, and a six-month follow up was completed. Results: The procedure-related complication rate was 16.7% in the cautery group, compared with 7.0% in the suture group (P < 0.05). The cerclage group had significantly shorter operative time and intraoperative blood loss than the cautery group (P < 0.05). Postoperative bleeding and dysmenorrhoea were observed in eight (10.2%), and 14 cases (17.9%), in cerclage and cautery group, respectively. Three cases (3.8%) had postoperative infections and were cured with oral antibiotics. Conclusions: These results suggest that cerclage suturing technique provided excellent haemostasis and restoration of normal cervical anatomy. Cerclage suture of the cone bed is superior to only cauterisation as a method of achieving haemostasis, with significantly less blood loss and shorter operative time. [source] Comparison of a self-administered tampon ThinPrep test with conventional pap smears for cervical cytologyAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2005Mardi BUDGE Abstract Aim: To assess a self-administered tampon specimen as an alternative method of detecting cytological abnormalities and its acceptability in comparison with a conventional Papanicolou (pap) smear. Design: Comparative observational study. Setting/population: Two hundred and seventeen women were recruited from the colposcopy clinic of an outer urban public teaching hospital and from sexual health clinics at suburban and major metropolitan hospital clinics. Methods: Participants inserted and immediately withdrew a tampon, then placed it into a vial of ThinPrep PreservCyt fluid. This was analysed by a local private pathology laboratory. Results were compared to a pap smear performed the same day or within the previous 6 months. All women with an abnormal result (tampon or pap smear) underwent a colposcopy, with or without biopsy as necessary. Participants completed a questionnaire after performing the tampon test. Outcome measures: Probabilities of tampon test detecting (i) a high grade abnormality (pHG), (ii) any cervical intraepithelial neoplasia (CIN) changes (pCINany), and (iii) any abnormalities (pabn) compared to the conventional pap smear and, if abnormal, compared to the biopsy taken at colposcopy. Acceptability of the tampon test and conventional pap smear were also measured. Results: Probabilities of the tampon test compared to pap smear: pabn sensitivity 33%, specificity 89%, PPV 59%, NPV 73%; pCINany sensitivity 23%, specificity 97%, PPV 71%, NPV 79%; pHG sensitivity 19%, specificity 98%, PPV 63%, NPV 89%. Acceptability for tampon test was 91.21% and for pap smear, 45.85%. Conclusions: Although the self-administered tampon ThinPrep method is a poor detector of cervical abnormalities compared to pap smear, it is highly acceptable to women. It has a relatively good negative predictive value (NPV). Our study suggests that if a more acceptable, sensitive method of cervical screening was found, which removed some of the existing barriers to conventional pap testing, screening rates for cervical cancer may improve. [source] Demographic variables routinely collected at colposcopic examination do not predict who will default from conservative management of cervical intraepithelial neoplasia IAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2005Julie A. QUINLIVAN Abstract Objective:, As a result of the low incidence of progression from low grade epithelial abnormalities to cervical intraepithelial neoplasia (CIN) 3 or cervical cancer, a conservative approach to management is supported, especially in young women. Loss to follow-up is a recognised problem with a conservative approach however, with women defaulting known to experience higher rates of cancer. Aim:, To determine if any routinely collected demographic variables could predict which Australian women would subsequently default from care having initially elected to have conservative management of CIN 1 lesions. Methods:, Prospectively collected data was audited on 279 women with a colposcopically directed biopsy diagnosis of CIN 1, confirmed on external review, who were enroled by their own choice into a conservative management program and monitored until a definitive lesion outcome was determined. Women who defaulted from follow-up and were lost to care providers despite follow-up appointments and reminder letters were compared to women who completed follow-up with either lesion resolution or progression requiring treatment, to establish if there were any demographic variables to predict default from care. Results:, Fifty-two (18.5%) women subsequently defaulted from follow-up. There were no significant differences in age, parity, proportion of women who were pregnant at diagnosis, smoking status, immunosuppressed or had a ,human papillomavirus (HPV) effect' reported on Pap-smear or colposcopic examination. Conclusion:, We cannot easily identify a subgroup of women who are more likely to default from follow-up of CIN 1 using routinely collected demographic data. Default from follow-up is a major risk with conservative approaches and further research to reduce default rates are required. [source] Performance of colposcopy in five sub-Saharan African countriesBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2009R Muwonge Objective, The performance of colposcopy provided in a screening study in five African countries was evaluated. Design, Cross-sectional study. Setting, Burkina Faso, Congo Brazzaville, Guinea Conakry, Mali and Niger. Population, Women aged 25,59 years. Methods, A total of 29 294 women participated in a cervical screening study in the five study sites, and newly trained local doctors performed colposcopy and directed biopsies as indicated. Using meta-analytical tools, four measures of colposcopy performance at different thresholds of colposcopic abnormalities were assessed. Sources of heterogeneity were also assessed. Main outcome measures, Proportions of women receiving biopsies, adequate biopsies and women diagnosed with cervical intraepithelial neoplasia (CIN). Results, Among 28 553 women with satisfactory colposcopy, 3101 had a colposcopic diagnosis of probable low-grade or worse lesions and 1128 probable high-grade or worse lesions. Overall, the measures that reached the set standards were proportion of biopsy taken at colposcopy threshold of probable high-grade or worse lesions (95%, 95% CI 90,100%) and proportion of adequate biopsy samples. The set standards were not met for the proportions of women diagnosed with CIN at different colposcopic abnormality thresholds. Detection of CIN2 or worse lesions increased with increasing colposcopic abnormality. Conclusions, The performance of colposcopy in some of the African sites studied was comparable to that previously observed in other studies. With appropriate training, monitoring, continuing practice and quality assurance, adequate standards of colposcopy can be attained in sub-Saharan Africa. [source] Characterising the local immune responses in cervical intraepithelial neoplasia: a cross-sectional and longitudinal analysisBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 13 2008YL Woo Introduction, Immunological competence influences the progression of cervical intraepithelial neoplasia (CIN) to invasive cancer. Information on the local immunological changes during the natural course of CIN is central for the development of new therapies. Objective, This study defines the populations of tissue-infiltrating immune cells in a cross-sectional cohort of different grades of CIN and also in a longitudinal cohort of regressing, persistent and progressing low-grade (LG)-CIN. Design, A cohort of 125 women with LG cytological atypia was recruited, of which 64/125 (51%) women with LG-CIN were followed prospectively for 1 year. Paraffin-embedded entry and exit cervical biopsies were used for immunohistochemistry analysis (CD4, CD8, CD56, FOXP3, CD1a and granzyme B). Results, At recruitment, 74/125 (59%), 39/125 (31%) and 12/125 (10%) women referred with LG smears had histologically proven LG-CIN, high-grade (HG) and normal biopsies, respectively. Seventeen of 64 (24.6%) women with LG-CIN progressed to HG-CIN within 1 year. In both LG-CIN and HG-CIN, the predominant intraepithelial cell population were cytotoxic T cells, while CD4+ and FOXP3+ T cells predominated the stromal compartment. Women with LG-CIN who later on regressed displayed a significantly higher number of cytotoxic (granzyme B+) cells in their entry samples. In addition, the ratio between CD8+ cells and granzyme B+ cells was close to 1, suggesting that all infiltrating CD8+ T cells were highly active. In contrast, this ratio was three-fold lower in women, in whom the lesions persisted or progressed. Conclusions, This study suggests that the early infiltration of lesions by highly cytotoxic effector cells protects against progression. [source] Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisationBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2006J Verguts Objectives, The aim of this study was to examine the accuracy of the presence of high-risk human papillomavirus (HR-HPV) DNA (HR-HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high-grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow-up cytology and the marginal status of the excised tissue. Design, Prospective follow-up study. Setting, Unselected women presenting at colposcopy clinic of University Hospital Gasthuisberg, Leuven. Population, Seventy-two women treated with conisation for CIN2 or CIN3. Methods, Women were followed by HR-HPV DNA test (Hybrid Capture II test of Digene®) every 3 to 6 months. The same vial was used for cytology and the HR-HPV DNA test (SurePathÔ). All women were further followed by colposcopy and cytology for 24 months at 6-month intervals. The outcome of the study was presence of >CIN2, proven with colposcopy-directed biopsy occurring within 24 months after treatment. HR-HPV status was correlated with recurrent or residual CIN2+. Main outcome measures, Sensitivity, specificity, predictive values and diagnostic odds ratios to predict treatment failure or cure were computed for HR-HPV testing, marginal status and follow-up cytology. HR-HPV status was also correlated with section margins postconisation and with the first cervical smear. Results, In 6 of the 72 treated women (8%), residual or recurrent CIN occurred. Women with recurrence were significantly older than women without a recurrence (51.5 ± 9.6 versus 39.8 ± 12.2 years, P= 0.007). All six women with recurrence were HR-HPV positive, four had a positive follow-up smear (,atypical squamous cells of uncertain significance = ASCUS+) and only two had involved section margins. Among the 66 cured women, 15 were HR-HPV positive, 6 had an abnormal smear and 12 had positive section margins. Sensitivity of cytology, positive section margins and HR-HPV DNA positivity was 66.7, 33.3 and 100% to predict treatment failure. Specificity of the three tests was, respectively, 90.9, 81.8 and 77.3%. Women with HR-HPV DNA at 3 to 6 months showed recurrent or residual CIN in 15% (2/13) if they had normal follow-up Pap smears and in 50% (4/8) if they had abnormal Pap smears. Margin status was not statistically significantly associated with human papillomavirus status. Conclusion, Persistence or clearance of HR-HPV DNA is an early valid prognostic marker of failure or cure after treatment for CIN2+ and is more accurate than cytology or section margin status at the time of conisation. The absence of HR-HPV DNA has a 100% negative predictive value. Higher age at conisation may be a previously unrecognised risk factor for recurrence. [source] | |||||||||||||||||||||||||||||||