Robin Crawford

A prospective study on the natural course of low-grade squamous intraepithelial lesions and the presence of HPV16 E2-, E6- and E7-specific T-cell responses.

This study investigates the clinical course of low grade squamous intraepithelial lesions (LSIL), HPV status and HPV16‐specific immune response in a large prospective study of 125 women with LSIL followed cytologically, virologically and histologically. Women with low‐grade abnormal smears were recruited and followed‐up for one year. Colposcopy, cervical biopsy for histology and brushings for HPV typing was performed at recruitment, 6 months (no biopsy) and upon completion of the study at one year. HPV16‐specific T‐cell responses were analysed by interferon‐γ ELISPOT at entry, 6 and 12 months. Infection with multiple HPV types was detected in 70% of all patients, HPV16 was found in 42% of the patients. LSIL lesions progressed to HSIL in 24%, persisted in 60% and regressed to normal in 16% of the patients. No difference was observed in the clearance rate of infections with single or multiple HPV types among the groups with a different histological outcome. HPV16‐specific type 1 T‐cell responses were detected in only half of the patients with an HPV16+ LSIL, and predominantly reactive to HPV16 E2 and E6. Interestingly, the presence of HPV16 E2‐specific T‐cell responses correlated with absence of progression of HPV16+ lesions (p = 0.005) while the detection of HPV16 E6 specific reactivity was associated with persistence (p = 0.05). This large prospective study showed that the majority of LSIL persisted or progressed within the first year.This was paralleled by immune failure as most of the patients with an HPV16+ LSIL failed to react to peptides of HPV16 E2, E6 or E7.

Can Optimal Primary Cytoreduction Be Predicted in Advanced Stage Epithelial Ovarian Cancer? Role of Preoperative Serum CA-125 Level

The aim of this study was to determine the ability of preoperative serum CA-125 levels to predict optimal cytoreduction in patients with stage III epithelial ovarian cancer. A retrospective review was made of the records of 40 patients with FIGO stage III ovarian carcinoma who underwent primary cytoreductive surgery. A receiver operating characteristic (ROC) curve was used to determine the most useful CA-125 level in predicting optimal versus suboptimal tumour cytoreduction. Twenty-two (55%) patients were optimally cytoreduced (residual disease ≤1 cm). A preoperative serum CA-125 level of 500 U/ml was found to be the value with the most predictive power. Optimal cytoreduction was obtained in 16 of the 21 cases (76%) with a CA-125 <500 U/ml compared to only 6 of the 19 cases (32%) with a CA-125 >500 U/ml. At this threshold, preoperative serum CA-125 level was able to predict optimal versus suboptimal cytoreduction with a sensitivity of 72%, specificity of 73%, positive predictive value of 68%, and negative predictive value of 76%. In the management of patients with advanced epithelial ovarian carcinoma, preoperative serum CA-125 level may help to predict optimal primary cytoreduction and to identify candidates for alternative approaches other than traditional primary cytoreductive surgery, such as neoadjuvant chemotherapy.

Characterising the local immune responses in cervical intraepithelial neoplasia: a cross-sectional and longitudinal analysis

Introductionu2002 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.

High prevalence of HPV in non-cervical sites of women with abnormal cervical cytology.

BackgroundHuman papillomaviruses (HPV) are causally associated with ano-genital and a subset of head and neck cancers. Rising incidence of HPV+ anal cancers and head and neck cancers have now been demonstrated in the developed world over the last decade. The majority of published data on HPV prevalence at the anal and oro-pharyngeal sites are from studies of higher-risk populations. There is a paucity of data on the prevalence of HPV at non-cervical sites in lower risk, non-HIV+ women and this study was designed to provide initial pilot data on a population of women recalled for colposcopy as part of the UK cervical screening programme.Methods100 non-HIV+ women with abnormal cervical cytology, attending clinic for colposcopic examination were recruited. Swabs from the oro-pharyngeal, anal and cervical sites were taken and DNA extracted. HPV detection and genotyping were performed using a standardised, commercially available PCR-line blot assay, which is used to genotype 37 HPV subtypes known to infect the ano-genital and oro-pharyngeal areas. Strict sampling and laboratory precautions were taken to prevent cross-contamination.ResultsThere was a very high prevalence of HPV infection at all three sites: 96.0%, 91.4% and 92.4% at the cervix, anus and oro-pharynx, respectively. Multiple HPV subtype infections were dominant at all 3 mucosal sites. At least one or more HR genotype was present at both the cervix/anus in 39/52 (75.0%) patients; both the cervix/oro-pharynx in 48/56 (85.7%) patients; and both the anus/oro-pharynx in 39/52 (75.0%) patients. HPV 16 infection was highly dominant across all mucosal sites, with over a 2-fold increase over the next most prevalent subtype (HPV 31).ConclusionsWomen with abnormal smears have widespread infection with high-risk HPV at the cervical, anal and oro-pharyngeal mucosal sites and may represent a higher risk population for HPV disease in the future.

FOXP3 immunohistochemistry on formalin-fixed paraffin embedded tissue- poor correlation between different antibodies.

Since its original description, there has been a substantial output of publications related to the FOXP3 gene. The FOXP3 protein, a member of the forkhead/winged-helix family of transcriptional regulators is a nuclear product and is not expressed in the cell cytoplasm or on the cell surface. Expression of this single transcription factor causes a developmental switch in naïve T cells to a suppressor cell phenotype, more commonly referred to as regulatory T cells (Tregs). Tregs have been intensively studied in various autoimmune diseases, infections and different cancers. An increasing choice of commercially available monoclonal antibodies targeting FOXP3 is now available. This report describes the experience of using two commonly used monoclonal FOXP3 antibodies on formalin-fixed paraffin-embedded sections of different organs, including the cervix and vulva. The antibodies targeting different FOXP3 epitopes unexpectedly resulted in significantly different staining patterns. This phenomenon has not been previously reported and is likely to be an important observation.

Long-term cytological and histological outcomes in women managed with loop excision treatment under local anaesthetic for high-grade cervical intraepithelial neoplasia

Y. L. Woo, C. Badley, E. Jackson and R. Crawford

Laparoscopic management of adnexal masses in adolescent females: a multidisciplinary approach

Laparoscopic surgery could be considered the gold standard in managing adnexal masses. The advantages of laparoscopic surgery have been proven in the adult population, and thus its use has been promoted for treating children and adolescents. However, although adolescent females should not be treated like children, their management differs from that of adults. We present three cases to illustrate how three adolescent girls had their adnexal masses dealt with laparoscopically. We recommend that hospitals consider a combined approach in the management of large adnexal masses in adolescents by utilising the expertise of the adolescent gynaecologist, gynaecology oncologist, and minimal access surgeon. In certain centres, a particular gynaecologist may possess all the skills required.

Virus-Induced Cancers of the Skin and Mucosa: Are We Dealing with “Smoking Guns” or “Smoke and Mirrors” in the Operating Theatre?

IntroductionHuman papillomavirus (HPV) alone is thought to cause ~610,000 cases of cancer per year, and is the dominant aetiological agent for ano-genital (esp. cervical) and head and neck cancers (esp. oropharyngeal). Merkel cell polyomavirus (MCV) is a more recently discovered virus which causes Merkel cell carcinoma, a rare but highly aggressive skin malignancy.MethodsWe explored the available published evidence to see if transmission of live HPV or MCV virus in smoke generated by laser or diathermy was feasible, and would pose an infection risk. Long-term infection with such carcinogenic viruses would then pose an increased risk for the development of virus-induced cancers in medical personnel.ResultsThe morphological structures of both HPV and MCV are very similar, and the size, external capsids and genomic structures show striking similarity. Both viruses have a non-enveloped external protein capsid consisting of 72 capsomeres, and a double-stranded DNA core. Sizes of both viruses range from 50 to 60xa0nm. There are now recent data demonstrating live and infectious HPV in smoke, and that these viruses can be used to infect cells in vitro. Further, anecdotal reports of virus transmission leading to disease causation in the production of respiratory airway viral warts (benign disease), and, finally, reports of HPV-induced oropharyngeal carcinoma (malignant disease) in two gynaecological surgeons as an occupational health hazard have been published recently.ConclusionThere is now sufficient evidence to support the hypotheses that live infectious carcinogenic viruses can be transmitted via smoke generated from surgical procedures, and, in rare instances, actually cause significant disease. Protective measures such as smoke extraction and airway protection should be instituted for all healthcare personnel, particularly those with multiple repeated exposures such as gynaecological surgeons.