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Biomedical subjects

H C Kitchener

Publications and source records attributed to H C Kitchener.

At least 19 recordsLinked to original sources
PubMed2006

HPV testing in routine cervical screening: cross sectional data from the ARTISTIC trial.

To evaluate the effectiveness of human papillomavirus (HPV) testing in primary cervical screening. This was a cross-sectional study from the recruitment phase of a prospective randomised trial. Women were screened for HPV in addition to routine cervical cytology testing. Greater Manchester, attendees at routine NHS Cervical Screening Programme. In all, 24 510 women aged 20-64 screened with liquid-based cytology (LBC) and HPV testing at entry. HPV testing in primary cervical screening. Type-specific HPV prevalence rates are presented in relation to age as well as cytological and histological findings at entry. In all, 24 510 women had adequate cytology and HPV results. Cytology results at entry were: 87% normal, 11% borderline or mild, 1.1% moderate and 0.6% severe dyskaryosis or worse. Prevalence of HPV decreased sharply with age, from 40% at age 20-24 to 12% at 35-39 and 7% or less above age 50. It increased with cytological grade, from 10% of normal cytology and 31% of borderline to 70% mild, 86% moderate, and 96% of severe dyskaryosis or worse. HPV 16 or HPV 18 accounted for 64% of infections in women with severe or worse cytology, and one or both were found in 61% of women with severe dyskaryosis but in only 2.2% of those with normal cytology. The majority of young women in Greater Manchester have been infected with a high-risk HPV by the age of 30. HPV testing is practicable as a primary routine screening test, but in women aged under 30 years, this would lead to a substantial increase in retesting and referral rates. HPV 16 and HPV 18 are more predictive of underlying disease, but other HPV types account for 30% of high-grade disease.

Adult↗
PubMed2006

The interval from surgery to chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

BACKGROUND: To study the effect of the interval between surgery and the start of chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS: We stratified patients according to the start of platinum-based chemotherapy in group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group 3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III ovarian cancer patients were analysed. In the multivariate analysis there were no differences in survival according to the interval between surgery and chemotherapy among the three groups. The independent prognostic variables were type of procedure (p = 0.014), performance status (p = 0.040) and post-chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and chemotherapy does not affect outcome.

Adult↗
PubMed2006

The IL-10 -1082G polymorphism is associated with clearance of HPV infection.

The role of cytokines in protecting against human papillomavirus (HPV) and HPV-associated disease is not fully understood. We compared the frequency of the interleukin (IL)-10 polymorphism (G allele) at position --1082 and the distribution of GG/GA/AA genotypes among 116 HPV-positive women, grouped according to their cervical cytological profiles, with 119 HPV-negative controls with normal smears. No difference was observed in genotype frequency between the groups. Among women in the HPV-positive, smear-normal group, who were re-tested for HPV after 12 months, there was a significant inverse association between presence of at least one variant G allele (high activity) and HPV persistence (OR per G allele = 0.082 [95% CI 0.009-0.73], P= 0.001; after controlling for ethnicity). This association remained significant after controlling for age, smoking and hormonal contraception (OR = 0.028 [95% CI 0.001-0.66], P= 0.001). This preliminary study suggests that higher levels of IL-10 may prevent cervical neoplasia through their role in eliminating HPV.

Adult↗
PubMed2006

Laparoscopic versus open colposuspension--results of a prospective randomised controlled trial.

OBJECTIVE: To compare the effectiveness and cost effectiveness of open and laparoscopic colposuspension in the treatment of stress urinary incontinence. DESIGN: A randomised controlled trial. Women were randomised between March 1999 and February 2002 and were seen for assessment at 6, 12 and 24 months, postoperatively. SETTING: Women were recruited from six gynaecology units in the UK. POPULATION: Women with proven stress urinary incontinence requiring surgery. METHODS: Open abdominal retropubic colposuspension or laparoscopic colposuspension. MAIN OUTCOME MEASURES: Primary outcomes were subjective (satisfaction with outcome) and objective (negative 1-hour pad test). Secondary outcomes were operative and postoperative morbidity and quality of life. The study was powered to demonstrate noninferiority, i.e. that the absolute cure rate of laparoscopic colposuspension was no more than 15% below that of open colposuspension. RESULTS: A total of 291 women were randomised, with 24-month data on subjective and objective outcomes in 88 and 82.5%, respectively. The intention-to-treat analysis indicated no significant difference in cure rates between open and laparoscopic surgery. The objective cure rates for open and laparoscopic were 70.1 and 79.7%, respectively. Subjective cure rates by satisfaction were lower than objective cure; 54.6 and 54.9%, respectively, and there was considerable nonconcordance both ways. CONCLUSIONS: Laparoscopic colposuspension is not inferior to open colposuspension in terms of curing stress urinary incontinence.

Female↗
PubMed2006

Cost-effectiveness analysis of open colposuspension versus laparoscopic colposuspension in the treatment of urodynamic stress incontinence.

OBJECTIVES: To compare the cost effectiveness of laparoscopic versus open colposuspension for the treatment of female urinary stress incontinence. DESIGN: Cost utility analysis alongside a randomised controlled trial. SETTING: Six gynaecological surgical centres within the UK. POPULATION/SAMPLE: Women with proven stress urinary incontinence requiring surgery. METHODS: Open abdominal retropubic colposuspension or laparoscopic colposuspension carried out by experienced surgeons. MAIN OUTCOME MEASURES: Cost, measured in pounds sterling and generic health-related quality of life, measured using the EQ-5D. The latter was used to estimate patient-specific quality-adjusted life years (QALYs). RESULTS: Healthcare resource use over 6-month follow up translated into costs of pound 1805 for the laparoscopic arm and pound 1433 for the open arm (differential mean cost pound 372; 95% credibility interval [CrI]: 274-471). At 6 months, QALYs were slightly higher in the laparoscopic arm relative to the open arm (0.005; 95% CrI: -0.012 to 0.023). Therefore, the cost of each extra QALY in the laparoscopic group (the incremental cost-effectiveness ratio [ICER]) was pound 74,400 at 6 months. At 24 months, the laparoscopic arm again had a higher mean QALY score compared to the open surgery group. Thus, assuming that beyond 6 months the laparoscopic colposuspension would not lead to any significant additional costs compared with open colposuspension, the ICER was reduced to pound 9300 at 24 months. Extensive sensitivity analyses were carried out to test assumptions made in the base case scenario. CONCLUSIONS: Laparoscopic colposuspension is not cost effective when compared with open colposuspension during the first 6 months following surgery, but it may be cost effective over 24 months.

Cost-Benefit Analysis↗
PubMed2005

The comparative diagnostic accuracy of conventional and liquid-based cytology in a colposcopic setting.

OBJECTIVE: This study was conducted to compare the performance of liquid-based cytology (LBC) and conventional cytology (CS) in the high prevalence setting of colposcopy clinic. DESIGN: A split sample of matched ThinPrep (TP) and conventional smear from 563 patients were evaluated blindly. The performance of both techniques was compared with the gold standard of biopsy results or normal colposcopy examination in 441 cases. SETTING: Colposcopy clinic of an inner city hospital for women and children. SAMPLE: Five hundred and sixty-three women referred to colposcopy clinic over 14-month period. METHODS: Cervical smears were taken from 563 women referred for colposcopy. Using the split-sample technique, the material was spread on a conventional (CS) slide and the remaining material rinsed in a PreservCyt solution. A T2000 processor was used to prepare LBC preparations. All women underwent colposcopy/biopsy according to local protocol. Four hundred and forty-one women met the diagnostic standard criteria of the study, which was either a normal colposcopy or histopathology result. Sensitivity, specificity and positive and negative predictive values were calculated for both methods of cytology preparations. MAIN OUTCOME MEASURES: Matched TP and conventional smears, detection of abnormality, matched biopsies, sensitivity, specificity, and positive and negative predictive values. RESULTS: Inadequate rates for CS and LBC (TP) were 4.3% and 0.68%, respectively. In 73% of cases, the CS and the LBC preparations showed exact agreement, whereas 77% agreement was seen when comparison was made for amalgamated low grade and high grade abnormalities. Low grade cytological abnormalities accounted for 44% of LBC slides versus 37% in CS slides. High grade cytological abnormalities accounted for 22% of LBC versus 17% seen in CS cases (P < 0.001). LBC showed increased sensitivity in the detection of CIN2 or worse than CS (92% and 83%, respectively) and CS showed greater specificity than LBC (82% and 76%, respectively). CONCLUSIONS: In high prevalence setting, LBC performed at least as well as CS. The inadequate rate was significantly lower with LBC. The numbers are too small, however, to make confident comments about increased sensitivity and negative predictive value with LBC. Larger studies are required to verify these findings.

Adult↗
PubMed2005

Biological and hormonal markers of chlamydia, human papillomavirus, and bacterial vaginosis among adolescents attending genitourinary medicine clinics.

OBJECTIVE: To assess maturity indices, menstrual patterns, hormonal factors, and risk of adolescent genital tract infections. METHODS: Cross sectional study in three genitourinary medicine clinics. Females 17 years or less, within 5 years of menarche, or reporting oligo-amenorrhoea were screened for genital tract infections and menstrual cycle characteristics determined. The outcome measures were risk factors associated with chlamydia, human papillomavirus (HPV DNA) and bacterial vaginosis (BV), separately and pooled. Correlations between estrone-3-glucuronide (E3G) and pregnanediol-3alpha-glucuronide (P3G) hormone concentrations and chlamydia, HPV, and BV. RESULTS: Among 127 adolescents, HPV was present in 64.4% (95% CI: 54.5 to 74.3), BV in 33.9% (19.1 to 34.5), and chlamydia in 26.8% (19.1 to 34.5). Breast maturity, oligomenorrhoea, and older gynaecological age were associated with lower risk of all infections. After adjustment for calendar age, race, and behavioural factors, gynaecological age remained significant (OR = 0.7, 0.6-0.9; p = 0.008). Behavioural risk factors differed by infection. Smoking was protective for HPV (OR = 0.1, 0.0 to 0.9; p = 0.007), and a recent new partner for chlamydia (OR = 0.3, 0.1 to 0.9; p = 0.024). Sex during menses was associated with increased BV risk (OR = 3.3, 1.5 to 7.2; p = 0.003). Chlamydia was higher among adolescents who used emergency contraception (2.5; 1.1 to 5.9, p = 0.029) and lower among those using condoms at last sex (OR = 0.3, 0.1 to 0.9; p = 0.015). Among 25 adolescents not using hormonal contraceptives, 15 had disturbed or anovulatory cycles. Chlamydia risk was inversely associated with P3G concentrations (Mann-Whitney; p = 0.05). CONCLUSIONS: Adolescents engaging in high risk behaviour at a young gynaecological age are susceptible to multiple infections. Adolescent clinical assessment should include gynaecological age.

Adolescent↗
PubMed2005

Factors affecting vaginal pH levels among female adolescents attending genitourinary medicine clinics.

OBJECTIVES: Vaginal pH is related to hormonal status, and adolescents experience disturbed hormonal patterns following menarche. We assessed hormonal factors and risk of abnormal vaginal pH and bacterial vaginosis (BV) among adolescents attending genitourinary medicine (GUM) clinics. METHODS: In a cross sectional study adolescents within 5 years of menarche, < or =17 years, or with oligo-amenorrhoea were recruited. Vaginal pH and BV were assessed and among those not using hormonal contraceptives, estrone-3-glucuronide (E3G) and pregnanediol-3alpha-glucuronide (P3G) concentrations were measured. RESULTS: Among 102 adolescents, 59.8% (61) had a high vaginal pH (>4.5), which was higher than the prevalence of BV, detected in 33% (34). No association was found between presence of sexually transmitted infections (STI) and vaginal pH. In logistic regression, after controlling for BV and condom use, vaginal pH was positively associated with cervical ectopy (OR = 2.5; 95% CI 1.0 to 6.6, p = 0.05) and STI treatment history (OR = 2.5; 95% CI 0.9 to 6.5, p = 0.07), and negatively associated with use of Depo-Provera (OR = 0.1; 95% CI 0.03 to 0.6, p = 0.003) and recent onset (<12 months) of sexual activity (OR = 0.2; 95% CI 0.1 to 0.7, p = 0.004). Among 23 adolescents not using hormonal contraceptives, a high pH occurred more often in abnormal compared to normal menstrual cycles (OR = 10.8; 95% CI 1.4 to 85.4; p = 0.026). E3G concentrations were inversely correlated with vaginal pH in the follicular phase (Spearman: r = 0.51; p = 0.024). CONCLUSIONS: Ectopy and abnormal menstrual cycles are common features of adolescence. Their presence is associated with increased risk of abnormal pH, and may also predispose to BV.

Adolescent↗
PubMed2004

Effect of TA-CIN (HPV 16 L2E6E7) booster immunisation in vulval intraepithelial neoplasia patients previously vaccinated with TA-HPV (vaccinia virus encoding HPV 16/18 E6E7).

Heterologous prime-boost vaccination schedules employing TA-HPV, a vaccinia virus encoding HPV 16/18 E6 and E7, in combination with TA-CIN, an HPV 16 L2E6E7 fusion protein, may offer advantages over the use of either agent alone for the immunotherapy of human papillomavirus (HPV) type 16-associated vulval intraepithelial neoplasia (VIN). In the present study, 10 women with HPV 16-positive high grade VIN, previously primed with TA-HPV, received three booster immunisations with TA-CIN. All but one demonstrated HPV 16-specific proliferative T-cell and/or serological responses following vaccination. Three patients additionally showed lesion shrinkage or symptom relief, but no direct correlation between clinical and immunological responses was seen.

Adult↗
PubMed2004

A randomised controlled trial of cytological surveillance versus patient choice between surveillance and colposcopy in managing mildly abnormal cervical smears.

OBJECTIVE: To determine whether choice of colposcopy or six month cytological surveillance would be beneficial to women with mildly abnormal smears when compared with the national policy of six months surveillance in terms of psychological morbidity. DESIGN: A randomised trial based on the Zelen design. SETTING: A hospital-based research clinic. POPULATION: Four hundred and seventy-six women who had had a recurrent borderline or mildly dyskaryotic smear on routine cervical screening in primary care. METHODS: Women were randomised either to six months cytological surveillance or to make a choice between that or colposcopy and were followed up for 1 year. MAIN OUTCOME MEASURES: The primary outcome measure was caseness (score >or=4) on the General Health Questionnaire at 12 months follow up. Other measures were the Spielberger State and Trait scores, default rates and cytology/colposcopy outcomes. RESULTS: There was no significant difference between the arms for General Health Questionnaire (GHQ) scores and Spielberger State and Trait at 12 months. There was a significant reduction in psychometric morbidity between baseline and 12 months in both arms. Overall rates of default from the protocol were the same in both arms, but default that led to uncertain ascertainment of cervical pathology was greater in the no-choice arm. CONCLUSIONS: This trial indicates that having choice did not impact favourably or harmfully on anxiety or feelings of wellbeing. If a patient is anxious, allowing the patient to choose immediate colposcopy may be preferable because it will improve ascertainment of underlying disease in a group who are more likely to default.

Adult↗
PubMed2004

Five-year follow-up of women with borderline and mildly dyskaryotic cervical smears.

This study investigated the 5-year follow-up status of women with cervical smears showing borderline nuclear changes (BNC) or mild dyskaryosis and the effect of koilocytosis on the outcome. Thirteen per cent of women with cervical smears showing BNC had high-grade cervical intraepithelial neoplasia (CIN). In contrast, 28% of women with cervical smears showing mild dyskaryosis had high-grade CIN. The presence of koilocytosis (24% for borderline smears and 34% for mild dyskaryotic smears) did not appear to influence the risk of developing high-grade CIN. Our results suggest that the simultaneous implementation of the British Society for Clinical Cytology proposed terminology and the colposcopy guidelines from the British Society for Colposcopy and Cervical Pathology could have an impact on colposcopy services.

Cell Nucleus↗
PubMed2003

Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia.

Vulval intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. To investigate the functional properties of VIN, the expression of several proteins involved in the regulation of the cell cycle as well as in situ DNA replication competence was analysed by immunohistochemistry. Snap-frozen vulval biopsies were graded as normal squamous epithelium (n=6), undifferentiated HPV positive VIN 1 (n=3), VIN 2 (n=8) and VIN 3 (n=20). Immunohistochemistry was performed using the following markers: cyclin D1 (expressed in middle/late G1), cyclin B1 (expressed in G2/early M), phosphorylated histone H3 (expressed during mitosis) and minichromosome maintenance (Mcm) proteins 2 and 5 (expressed during the cell cycle, but not in differentiated or quiescent cells). In situ DNA replication competence was used to identify S-phase cells. The percentage of positively stained nuclei in three representative microscopic fields was calculated per biopsy. In normal vulva, the expression of all markers was restricted to the proliferative compartment of the basal layer of the epithelium. In contrast in high-grade VIN, the majority of epithelial cells expressed the Mcm proteins from basal to superficial layer. The detection of cyclins B1 and D1, phospho-histone H3 and in situ DNA replication was also found through the full thickness of these lesions but by a lower proportion of the cells. This is consistent with these markers providing a series of 'snapshots' of the cell cycle status of individual cells. The low-grade VIN showed reduced expression of the cell cycle markers in relation to the level of dysplasia. The combination of these analyses establishes that the majority of VIN cells remain in a functional replicative or prereplicative state of the cell cycle. Clinical application of these analyses may provide a basis for improved diagnosis of VIN.

Biomarkers, Tumor↗
PubMed2002

Identification of inguinal lymph node metastases from vulval carcinoma by magnetic resonance imaging: an initial report.

AIM: Magnetic Resonance Imaging (MRI) has the potential to assess inguinal lymph nodes more accurately than palpation and less invasively than surgical exploration. The objective of this study was to measure the accuracy of MRI in identifying inguinal metastases by demonstrating abnormal lymph node morphology. MATERIALS AND METHODS: 10 women with vulval malignancy underwent T1- and fat-suppressed T2-weighted surface coil MRI of both groins before surgery. Each groin was prospectively categorised as normal or as having metastatic lymphadenopathy using criteria established in normal volunteers. Histopathological findings in patients undergoing groin dissection for invasive vulval carcinoma were used as validation. RESULTS: MRI had a positive predictive value of 89%, negative predictive value of 91%, sensitivity of 89%, specificity of 91% and accuracy of 90%. The most useful observations on MRI to identify metastatic lymphadenopathy were those of lymph node contour irregularity, cystic change in a lymph node, short axis diameter exceeding 10mm and abnormal long: short axis diameter ratio. CONCLUSION: High resolution MRI of the inguinal regions has potential to screen for lymph node metastases in patients with vulval cancer, with the aim of reducing the number of women who have to undergo groin dissection.

Adult↗
PubMed2001

Human T cell responses to HPV 16 E2 generated with monocyte-derived dendritic cells.

Persistent infection with human papillomavirus (HPV) type 16 has been implicated in the etiology of cervical cancer. The E2 protein is required early in viral infection and therefore may serve as a useful immune target for a vaccine aimed at prevention or therapy of premalignant lesions. Dendritic cells (DC) prepared from monocytes and pulsed with bacterially produced HPV 16 E2 C-terminus protein were used to stimulate autologous T cells over several rounds of stimulation. T cells were tested for gamma-interferon release by ELISPOT and for cytotoxic activity by (51)chromium release assays. To generate E2-expressing target cells for cytotoxicity assays, we constructed a recombinant vaccinia virus encoding HPV 16 E2, which was used to infect autologous Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL). The results show that DC pulsed with E2 C-terminus protein induce gamma-interferon-releasing T cells as demonstrated by ELISPOT. Furthermore, we demonstrate E2-specific lysis of vaccinia-E2 infected autologous LCL by CD8+ cytotoxic T lymphocytes (CTL). E2-specific CTL did not lyse untreated autologous LCL or LCL infected with wild-type vaccinia and showed low levels of cytotoxicity against natural killer cell-sensitive K562 cells. In addition, T cells stimulated with DC in the absence of E2 failed to demonstrate lysis of vaccinia-E2-labeled targets. Phenotypically, CTL populations were CD3+/CD8+. These results will facilitate the study of naturally occurring T-cell responses to HPV E2 in patients with cervical intraepithelial neoplasia and the development of immunotherapeutic strategies designed to treat this and other HPV-associated diseases.

Cytotoxicity, Immunologic↗
PubMed2001

Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy.

Topical 5-aminolevulinic acid-based photodynamic therapy (PDT) has produced complete response rates of >90% for nonmelanoma skin carcinomas, which are mostly human papillomavirus (HPV) negative. Using a similar treatment protocol, we observed a short-term response in only one third (10 of 32) of high-grade vulval intraepithelial neoplasia (VIN 2-3) lesions. Unifocal lesions were found more responsive than multifocal and pigmented lesions. Animal model studies have suggested that long-term PDT response involves an immune reaction in which CTLs play a crucial role. In this study, we have assessed: (a) HPV infection; (b) HLA expression; and (c) immune infiltrating cells in VIN biopsies from responders and nonresponders to determine whether these factors may limit response to topical 5-aminolevulinic acid-based PDT. Tissues from normal vulva (n = 9), vulval carcinoma (n = 11), and VIN (32 patients from which 19 pre- and 43 post-PDT biopsies were taken) were investigated for immune cell infiltration and HLA class I expression by immunohistochemistry and HPV infection by PCR. There was a greater likelihood of HPV positivity associated with a lack of response of VIN to PDT (P = 0.002), and VIN nonresponders were more likely to show HLA class I loss compared with responders (P = 0.030). HLA class I down-regulation was significantly greater in the carcinomas (82%, total loss) than the VIN (28%, 19%, total loss; and 9%, allele loss; P = 0.004). None of the cases with class I down-regulation responded to PDT, whereas 3 of 6 (50%) of cases that showed total class I loss subsequently developed superficial invasion. Compared with normal vulval skin, VIN lesions showed increased infiltration by CD4 (T-helper) and CD68 (macrophages) but not CD1a (Langerhans cells) or CD8 (CTLs). There was, however, a significant increase of CD8 infiltration in posttreatment VIN responders compared with nonresponders (P = 0.0001). These data clearly support the contention that high-risk HPV infection and lack of cell-mediated immunity may play a role in the observed poor response of lower genital lesions to topical PDT.

Adolescent↗
PubMed2001

Human papillomavirus testing and the outcome of treatment for cervical intraepithelial neoplasia.

OBJECTIVE: To investigate whether human papillomavirus (HPV) testing could be used in the follow-up after large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia (CIN). METHODS: We performed a retrospective study of 41 women who developed subsequent CIN after LLETZ (group A) and 82 women without CIN for a minimum of 5 years after LLETZ (group B). The first post-treatment cervical smear was retrieved and examined for high-risk HPV deoxyribonucleic acid. The sensitivity, specificity, positive and negative likelihood ratio of HPV testing, first post-treatment Papanicolaou test, and excision margins for the detection of treatment failure were calculated. Multiple logistic regression analysis was also done. RESULTS: The HPV test was positive in 38 of 41 women in group A and 13 of 82 in group B (P <.001). An abnormal cytologic result in the first post-treatment smear was found in 20 of 41 in group A and 11 of 82 in group B (P <.001). Sixteen women in group A and 18 in group B had involved margins (P =.046). Values for the sensitivity, specificity, and positive and negative likelihood ratios of the HPV test were 93%, 84%, 5.8, 0.08; for the Papanicolaou test they were 49%, 87%, 3.9, 0.586; and for margin status they were 39%, 78%, 1.8, 0.782, respectively. Positive HPV test presents significantly high odds ratio for treatment failure (P <.001), independent of cytology and margin status. CONCLUSION: Women who postoperatively have positive HPV testing are at higher risk of treatment failure. This could be performed at the first post-treatment visit and further follow-up could be adjusted accordingly.

Adult↗