Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Under expression of the Sonic Hedgehog receptor, Patched1 (PTCH1), is associated with an increased risk of local recurrence in squamous cell carcinoma of the vulva arising on a background of Lichen Sclerosus.

OBJECTIVE: Dysregulation of the Hedgehog (Hh) pathway has been described in a variety of cancers, including cervical cancer, a disease which shares a common aetiology with vulval squamous cell carcinoma (VSCC). Here, we investigate a large number of primary VSCC cases for evidence of Hedgehog pathway activation and examine the implications of pathway activity on clinical outcomes in a cohort of patients with primary VSCC. METHODS: Archival histology blocks containing VSCC and histologically normal adjacent epithelium were retrieved from a cohort of 91 patients who underwent treatment for primary VSCC. Immunohistochemistry staining was undertaken to assess for the expression of key Hh pathway components (SHH, PTCH1, GLI1). A competing risks statistical model was used to evaluate the implications of the levels of key Hh pathway components on clinical outcomes. RESULTS: We show that 92% of primary VSCC cases over-expressed one or more components of the Hh signalling pathway when compared to the adjacent normal epithelium. While expression of SHH and GLI1 did not correlate with any clinicopathological criteria, over- or under-expression of PTCH1 was associated with a reduced or increased risk of developing a local disease recurrence, respectively. In VSCC arising on a background of Lichen Sclerosus, the risk of local recurrence was potentiated in cases where PTCH1 was under-expressed. CONCLUSIONS: Our findings reveal, for the first time, that the Hh pathway is activated in VSCC and that PTCH1 expression can be used as a biomarker to stratify patients and inform clinicians of the risk of their local recurrence, particularly in cases of VSCC associated with LS.

A survey on the use of topical steroids in patients treated for lichen sclerosus-associated vulval squamous cell carcinoma.

Evidence suggests that lichen sclerosus (LS) is the primary aetiological factor for local vulval recurrence (LVR) in vulval squamous cell carcinoma (VSCC). The long-term application of topical corticosteroids is believed to prevent LVR. Patients treated for LS-associated VSCC at a gynaecological cancer centre were invited to complete a questionnaire to evaluate whether they are receiving corticosteroids. 55 of the 95 eligible patients (58%) completed the questionnaire; LS was treated in 69%, with steroids given to 84.2%. Most received steroids >3 months, but discontinued treatment once asymptomatic. An online survey was distributed to 313 British Gynaecological Cancer Society members to determine whether gynaecological oncologists prescribe corticosteroids for LS following VSCC surgery. 41 consultants (13.1%) completed the survey; 70.7% prescribe topical corticosteroids (potent/very potent in 79.3%), and 58.6% treat >1 year. Our findings demonstrate that patients are more likely to be given topical corticosteroids if symptomatic of LS. Furthermore, although treatment regimens vary, the majority of respondents advocate the use of very potent steroids and would support a tertiary chemopreventative trial. Impact statement What is already known on this subject: Local vulval recurrence (LVR) affects approximately one in four women who have received surgery for vulval squamous cell carcinoma (VSCC). What the results of this study add: Lichen sclerosus (LS), an inflammatory dermatosis, is recognised as the likely primary aetiological factor for LVR. Although there is evidence to suggest that long-term topical corticosteroid use in patients with residual LS may prevent LVR, the extent to which women were given topical steroids following surgery remains unclear. Our patient questionnaire evaluates if these patients are already receiving topical steroids, along with the strength of such steroids and duration of treatment. The consultant survey determines whether clinicians currently prescribe topical steroids following VSCC surgery, as well as the strength and duration of steroid therapy. What the implications are of these findings for clinical practice and/or further research: We aim to establish whether the gynaecological oncology community believe that long-term steroids may prevent LVR in women with LS-associated VSCC and whether they would support and recruit to a multicentre tertiary chemopreventative trial. These findings could influence a future clinical trial and may alter the ongoing management of these women.

Over-expression of DNMT3A predicts the risk of recurrent vulvar squamous cell carcinomas.

OBJECTIVE: Cancer initiation and progression has been linked to aberrant expression of the DNA methyltransferases (DNMT), the enzymes which establish and maintain DNA methylation patterns throughout the genome. In this study, we investigated if DNMT expression in vulvar squamous cell carcinomas (VSCC) was related to clinical outcome. METHODS: DNMT1, DNMT3A and DNMT3B expression was measured in a subset of cases drawn from a cohort of consecutive women treated for primary VSCC at the Pan Birmingham Gynaecological Cancer Centre between 2001 and 2008. Univariable and multivariable competing risk modelling was performed to identify whether DNMT expression was associated with local disease recurrence or disease morbidity. RESULTS: Over-expression of DNMT3A in the invasive component of the tumour was seen in 44% of tumours and was associated with an increased risk of local vulvar recurrence (LVR) (HR=4.51, p=0.012). This risk was found to increase further after adjustment for disease stage (HR=6.00, p=0.003) and groin node metastasis (HR=4.81, p=0.008). Over-expression of DNMT3B was associated with an increased risk of LVR (HR=5.69 p=0.03), however this ceased to be significant after adjustment for groin node metastasis. In a subset analysis, over-expression of DNMT3A was found to be significantly more common in VSCCs that stained negative for CDKN2A. CONCLUSIONS: These observations are consistent with the possibility that epigenetic changes contribute to vulvar neoplasia and DNMT3A over-expression may be useful in predicting local disease recurrence.

Vulval and vaginal cancer in pregnancy.

Lower genital tract malignancy during pregnancy is rare. Due to the rarity of this condition, the best evidence in its management is based on case reports. The management of the lower genital tract malignancy is influenced by factors including oncological factors, maternal and foetal effect of treatment, and other religious and ethical issues in a multidisciplinary approach. In most cases, the woman can continue with the pregnancy. This chapter describes the management of vaginal and vulval cancer during pregnancy based on available case reports.

Patient-Reported Outcomes After Extensive (Ultraradical) Surgery for Ovarian Cancer: Results From a Prospective Longitudinal Feasibility Study.

BACKGROUND: Extensive (ultraradical) surgery may facilitate complete cytoreduction in ovarian cancer with potential survival benefit but with greater morbidity. Currently, patient-reported outcomes (PROs) from such surgery are unknown. We conducted the Surgery in Ovarian Cancer Quality of life Evaluation Research study (SOCQER 1), a prospective study investigating the feasibility of collection of serial PROs in patients who had extensive surgery and standard surgery for ovarian cancer. METHODS: Ninety-three patients were recruited for 33 months to complete serial PRO assessments using the validated EORTC QLQ-C30 and the ovarian cancer-specific QLQ-OV28 questionnaires preoperatively, at 6 weeks, and at 3, 6, and 9 months postoperatively. Aletti Surgical Complexity Score of 3 or lower was considered standard surgery; a Surgical Complexity Score of 4 or higher was considered extensive surgery. Prospective data collection was obtained from the hospital electronic database, including patient demographics, American Society of Anaesthesiologists grade, preoperative serum CA125 and albumin levels, chemotherapy regimen, and surgical morbidity. RESULTS: Three cohorts of patients--32 benign, 32 undergoing standard surgery, and 24 undergoing extensive surgery--completed the questionnaires. Median questionnaire completion rate in this study was 64%, demonstrating the feasibility of longitudinal quality of life (QoL) assessment after surgery. Patient-reported outcomes revealed a falling trend in QoL in the short-term (6 weeks-3 months) after surgery, which gradually returned to baseline at 6 to 9 months; this trend was more marked after extensive surgery. CONCLUSIONS: This study provides useful insight into the impact of extensive surgery on patients. Further multicenter studies are needed to evaluate the impact of extensive surgery on patient's QoL and survival.

Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial.

BACKGROUND: The international standard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy. We aimed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen. METHODS: In this phase 3, non-inferiority, randomised, controlled trial (CHORUS) undertaken in 87 hospitals in the UK and New Zealand, we enrolled women with suspected stage III or IV ovarian cancer. We randomly assigned women (1:1) either to undergo primary surgery followed by six cycles of chemotherapy, or to three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2), or an alternative carboplatin combination regimen, or carboplatin monotherapy. We did the random assignment by use of a minimisation method with a random element, and stratified participants according to the randomising centre, largest radiological tumour size, clinical stage, and prespecified chemotherapy regimen. Patients and investigators were not masked to group assignment. The primary outcome measure was overall survival. Primary analyses were done in the intention-to-treat population. To establish non-inferiority, the upper bound of a one-sided 90% CI for the hazard ratio (HR) had to be less than 1.18. This trial is registered, number ISRCTN74802813, and is closed to new participants. FINDINGS: Between March 1, 2004, and Aug 30, 2010, we randomly assigned 552 women to treatment. Of the 550 women who were eligible, 276 were assigned to primary surgery and 274 to primary chemotherapy. All were included in the intention-to-treat analysis; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per-protocol analysis. As of May 31, 2014, 451 deaths had occurred: 231 in the primary-surgery group versus 220 in the primary-chemotherapy group. Median overall survival was 22.6 months in the primary-surgery group versus 24.1 months in primary chemotherapy. The HR for death was 0.87 in favour of primary chemotherapy, with the upper bound of the one-sided 90% CI 0.98 (95% CI 0.72-1.05). Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary-surgery group than in the primary-chemotherapy group (60 [24%] of 252 women vs 30 [14%] of 209, p=0.0007, and 14 women [6%] vs 1 woman [<1%], p=0.001). The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups (8 women [3%] in the primary-surgery group vs 14 [6%] in the primary-chemotherapy group). 110 (49%) of 225 women receiving primary surgery and 102 (40%) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect (p=0.0654), mostly uncomplicated neutropenia (20% and 16%, respectively). One fatal toxic effect, neutropenic sepsis, occurred in the primary-chemotherapy group. INTERPRETATION: In women with stage III or IV ovarian cancer, survival with primary chemotherapy is non-inferior to primary surgery. In this study population, giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer. FUNDING: Cancer Research UK and the Royal College of Obstetricians and Gynaecologists.

Vaginoplasty: a modern approach: a report of 2 cases.

BACKGROUND: Split-thickness skin graft vaginoplasty is one of many methods for vaginal reconstruction. In its 130-year history it has been modified by numerous authors in attempts to improve graft viability and neovaginal function. We describe a modern approach that aims to improve outcomes and reduce complications. CASES: Two cases of split-thickness skin graft vaginoplasty are presented in which the traditional Abbé-McIndoe technique was supplemented by the combined use of vacuum-assisted closure and fibrin tissue sealant. In both cases 100% graft survival and normal neovaginal function were observed, with no recipient site complications. Both patients mobilized on postoperative day 3, and both were sexually active 4 months postoperatively. CONCLUSION: This approach has not been described previously in the literature. The impressive results seen in these cases suggest that the use of vacuum-assisted closure and fibrin tissue sealant in combination may improve graft survival and resulting neovaginal function.

Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis.

OBJECTIVE: The objective of the study was to evaluate the regression, relapse, and live birth rates of early-stage endometrial cancer (EC) and atypical complex hyperplasia (ACH) with fertility-sparing treatment. STUDY DESIGN: This was a metaanalysis of the proportions from observational studies with a random-effects model and a meta-regression to explore for heterogeneity. RESULTS: Thirty-four observational studies, evaluating the regression, relapse, and live birth rates of early-stage EC (408 women) and ACH (151 women) with fertility-sparing treatment. Fertility-sparing treatment for EC achieved a pooled regression rate of 76.2%, a relapse rate of 40.6%, and a live birth rate of 28%. For ACH the pooled regression rate was 85.6%, a relapse rate of 26%, and a live birth rate of 26.3%. Twenty women were diagnosed with ovarian cancer (concurrent or metastatic) during follow-up (3.6%) and 10 progressed to higher than stage I EC (1.9%) from which 2 women died. CONCLUSION: Fertility-sparing treatment of EC and ACH is feasible and selected women can satisfy their reproductive wishes.

Radiotherapy and chemoradiation after surgery for early cervical cancer.

BACKGROUND: This is an updated version of the original Cochrane review first published in Issue 4, 2009. There is an ongoing debate about the indications for, and value of, adjuvant pelvic radiotherapy after radical surgery in women with early cervical cancer. Certain combinations of pathological risk factors are thought to represent sufficient risk for recurrence, that they justify the use of postoperative pelvic radiotherapy, though this has never been shown to improve overall survival, and use of more than one type of treatment (surgery and radiotherapy) increases the risks of side effects and complications. OBJECTIVES: To evaluate the effectiveness and safety of adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, chemoradiation) after radical hysterectomy for early-stage cervical cancer (FIGO stages IB1, IB2 or IIA). SEARCH METHODS: For the original review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 4, 2008. The Cochrane Gynaecological Cancer Group Trials Register, MEDLINE (January 1950 to November 2008), EMBASE (1950 to November 2008). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For this update, we extended the database searches to September 2011 and searched the MetaRegister for ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, or chemoradiation) with no radiotherapy or chemoradiation, in women with a confirmed histological diagnosis of early cervical cancer who had undergone radical hysterectomy and dissection of the pelvic lymph nodes. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Information on grade 3 and 4 adverse events was collected from the trials. Results were pooled using random-effects meta-analyses. MAIN RESULTS: Two RCTs, which compared adjuvant radiotherapy with no adjuvant radiotherapy, met the inclusion criteria; they randomised and assessed 397 women with stage IB cervical cancer. Meta-analysis of these two RCTs indicated no significant difference in survival at 5 years between women who received radiation and those who received no further treatment (risk ratio (RR) = 0.8; 95% confidence interval (CI) 0.3 to 2.4). However, women who received radiation had a significantly lower risk of disease progression at 5 years (RR 0.6; 95% CI 0.4 to 0.9).Although the risk of serious adverse events was consistently higher if women received radiotherapy rather than no further treatment, these increased risks were not statistically significant, probably because the rate of adverse events was low. AUTHORS' CONCLUSIONS: We found evidence, of moderate quality, that radiation decreases the risk of disease progression compared with no further treatment, but little evidence that it might improve overall survival, in stage IB cervical cancer. The evidence on serious adverse events was equivocal.

Is gynaecological surgical training a cause for concern?: a questionnaire survey of trainees and trainers.

BACKGROUND: Concerns have been raised as to whether the current postgraduate training programme for gynaecological surgery is being detrimentally affected by changes in working practices, in particular the European Working Time Directive (EWTD). The purpose of this study was to investigate the surgical activity of obstetrics and gynaecology trainees and to explore trainees' and trainers' opinions on the current barriers and potential solutions to surgical training. METHODS: Two questionnaire surveys were conducted, one to obstetrics and gynaecology trainees working within the West Midlands Deanery and a second to consultant gynaecologists in the West Midlands region. RESULTS: One hundred and four trainees (64.3%) and 66 consultant gynaecologists (55.0%) responded. Sixty-six trainees (66.7%) reported attending up to one operating list per week. However, 28.1% reported attending up to one list every two weeks or less and 5 trainees stated that they had not attended a list at all over the preceding 8 weeks. Trainees working in a unit with less than 3999 deliveries attended significantly more theatre sessions compared to trainees in units with over 4000 deliveries (p = 0.007), as did senior trainees (p = 0.032) and trainees attached to consultants performing major gynaecological surgery (p = 0.022). In the previous 8 weeks, only 6 trainees reported performing a total abdominal hysterectomy independently, all were senior trainees (ST6 and above). In the trainers' survey, only two respondents (3.0%) agreed that the current program produces doctors competent in general gynaecological surgery by the end of training, compared to 48 (73.8%) respondents who disagreed. CONCLUSIONS: Trainees' concerns over a lack of surgical training appear to be justified. The main barriers to training are perceived to be a lack of team structure and a lack of theatre time.

Women's experience of colposcopy: a qualitative investigation.

BACKGROUND: The last comprehensive investigation of women's experience of the colposcopy service in the UK was conducted in the 1980's. It highlighted women's anxiety and lack of information, resulting in recommendations for improvements. Since then the colposcopy service has changed substantially. It is therefore time to re-visit women's experience of this service and reflect upon the success of service changes in improving experience and reducing anxiety. The aim of this study was to investigate women's experience of being referred for, and attending, colposcopy appointments, and identify potential service improvements. METHODS: Qualitative in-depth interviews were conducted with 18 women newly referred for colposcopy in the West Midlands, UK. The interviews were designed to elicit the experience of colposcopy from the patients' perspective. RESULTS: The eight emerging themes were categorised as three overarching concepts, which were: feelings of emotional reaction, choices being accommodated and time delays. Women felt very apprehensive before their appointment, but when attending, appreciated being consulted about their preferences. Delays in referral and feeling 'rushed' by staff impacted negatively on women's experience. CONCLUSIONS: Service changes in information provision and increased respect for dignity seem to have improved the experience that women have of colposcopy, however, this does not appear to have translated into decreased anxiety. Women still have strong emotional reactions to being referred for, and attending, colposcopy appointments. Staff taking time to explain the diagnosis fully, and discuss their preferences about aspects of their consultation can alleviate their anxiety.

Adverse outcomes after colposcopy.

BACKGROUND: Colposcopy is an essential part of the National Health Service Cervical Screening Programme (NHSCSP). It is used for both diagnosis and treatment of pre-cancerous cells of the cervix. Despite colposcopy being a commonly performed and relatively invasive procedure, very little research has explored the potential long-term impacts of colposcopic examination upon patient quality of life.The aim of this study is to investigate and quantify any potential reduction in women's quality of life following a colposcopy procedure. More specifically, the degree of female sexual dysfunction and the excess risk of adverse events in those undergoing colposcopy will be explored. If such risks are identified, these can be communicated to women before undergoing colposcopy. It will also assist in identifying whether there are particular sub-groups at greater risk and if so, this may lead to a re-evaluation of current recommendations concerning colposcopically directed treatments. METHODS/DESIGN: Cohort study using postal surveys to assess sexual function and quality of life in women who have attended for colposcopy (cases), compared with those who have not attended colposcopy (controls). The prevalence and excess risk of female sexual dysfunction will be determined. Logistic regression will identify the predictors of adverse outcomes. DISCUSSION: There are more than 400,000 colposcopy appointments each year in England, of which 134,000 are new referrals. There is some evidence that there may be long-term implications for women treated under colposcopy with respect to adverse obstetric outcomes, persisting anxiety, increased rates of sexual dysfunction and reduced quality of life. Reliably establishing whether such adverse outcomes exist and the excess risk of adverse events will facilitate informed decision-making and patient choice.

Indication and outcome of repeat large loop excision biopsies of the cervix.

INTRODUCTION: To investigate the indications for performing a second large loop excision of the transformation zone (LLETZ) biopsy and to compare the associated colposcopic and pathological findings and treatment morbidity compared with 1 LLETZ. METHODS: This is a case-control study that reviewed case notes and histology reports on women who had undergone 1 LLETZ biopsy (control group) and women who had undergone 2 biopsies (index group). A comparison of referral cytology, colposcopic findings, and pathological and clinical outcomes was performed. RESULTS: Of the women who went on to have 2 LLETZ biopsies, 88% had histologically proven high-grade cervical intraepithelial neoplasia (CIN) or invasion on their first biopsy. A significantly greater proportion of high-grade cytologic and histologic diagnoses were associated with the first LLETZ compared with the second LLETZ biopsy, 76.5% and 69.1% versus 39.5% and 30.9%, respectively. A significantly greater proportion of women in the control group were referred with low-grade cytology (28.0%) and were diagnosed with human papillomavirus/low-grade CIN on histology (31.7%) compared with the first cytologic and LLETZ results in the index group, 9.9% and 8.6%, respectively. Complications were low in both groups; the immediate complication rate was 4% after the first LLETZ compared with 1% after the second LLETZ. CONCLUSIONS: Most second LLETZ biopsies are performed in women with a history of biopsy-proven high-grade CIN and are not associated with an increased risk of immediate complications.

The British Gynaecological Cancer Society Delphi consultation exercise on expected standards of practice for doctors specializing in the area of gynecological oncology.

OBJECTIVE: To determine a set of auditable standards applicable to physicians working in the area of gynecological oncology, which could be implemented as accreditation criteria for the revalidation procedure. DESIGN: A 3-round Delphi consultation exercise. SETTING: British Gynaecological Cancer Society (BGCS) members and delegates at the 2006 and 2007 Annual BGCS conferences Population 35 BGCS members, 72 delegates attending the 2006 BGCS conference and 120 delegates attending the 2007 conference. METHODS: A preliminary Delphi consultation of members was performed electronically to determine the contents of the final Delphi questionnaires. Prioritization was achieved by scoring each parameter on a 5-point Likert scale. MAIN OUTCOME MEASURE: The mean score awarded to each benchmarking parameter and the identification of parameters scoring 4 or above 75% or more of the respondents. RESULTS: The first round contained responses from 68 participants in stage 1 and 72 in stage 2. The second round included 120 participants. Nine of the auditable standards in first round and 10 in the second round achieved a score of 4 or above 75% or more of the participants and were therefore considered to be essential for revalidation. The selected criteria focused on an individual clinician's caseload and performance, multidisciplinary team working and continued professional development. CONCLUSIONS: This study has used the Delphi technique to identify auditable standards which could be used in the revalidation process of physicians working in the area of gynecological cancer.

Stage IA2 cervical carcinoma: how much treatment is enough?

OBJECTIVE: The current guidance for the management of women with stage IA2 cervical carcinoma is that whatever the primary surgical intervention, pelvic lymphadenectomy should be included. The role of lymphadenectomy in the management of cervical carcinoma remains somewhat confused, as the procedure has not been proven to be therapeutic, although it is claimed that the information gained is valuable in determining the need for adjuvant therapy. For lymphadenectomy to have clinical utility in the care of women with stage IA2 cervical carcinoma, a sufficiently high incidence of node positivity would be required to justify the morbidity of the procedure for the whole group. The objective of this paper was to establish the incidence of pelvic lymph node positivity in stage IA2 cervical carcinoma. METHODS: A PubMed search using the words "stage IA2 cervical carcinoma," "microinvasive cervical carcinoma," "stage IA cervical carcinoma," "stage I cervical carcinoma," and "lymphadenectomy in cervical carcinoma" was performed; the articles were divided into those that adhered to the International Federation of Gynecology and Obstetrics (FIGO) definition of a stage IA2 tumor and those that did not. Sentinel node studies were not included, as this procedure does not form part of the FIGO guidelines. RESULTS: Studies adhering to the FIGO definition showed a 0.5% incidence of lymph node metastases in stage IA2 cervical carcinomas, which is not as high as was previously believed (7.3%). CONCLUSIONS: The very low rate of positive lymph nodes in correctly staged IA2 cases cannot justify the inclusion of lymphadenectomy as part of standardized care for these patients.

Adjuvant radiotherapy and chemoradiation after surgery for cervical cancer.

BACKGROUND: There is an ongoing debate about the indications for, and value of, adjuvant pelvic radiotherapy after radical surgery in women with early cervical cancer. Certain combinations of pathologic risk factors are thought to represent sufficient risk for recurrence, that they justify the use of post-operative pelvic radiotherapy, though this has never been shown to improve overall survival, and use of more than one type of treatment (surgery and radiotherapy) increases the risks of side-effects and complications. OBJECTIVES: To evaluate the effectiveness and safety of adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, chemoradiation) after radical hysterectomy for early stage cervical cancer (FIGO stages IB1, IB2 or IIA). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 4, 2008. The Cochrane Gynaecological Cancer Group Trials Register, MEDLINE (January 1950 to November 2008), EMBASE (1950 to November 2008). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, or chemoradiation) with no radiotherapy or chemoradiation, in women with a confirmed histological diagnosis of early cervical cancer who had undergone radical hysterectomy and dissection of the pelvic lymph nodes. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Information on grade three and four adverse events was collected from the trials. Results were pooled using random effects meta-analyses. MAIN RESULTS: Two RCTs, which compared adjuvant radiotherapy with no adjuvant radiotherapy, met the inclusion criteria; they randomised and assessed 397 women. Meta-analysis of these two RCTs indicated no significant difference in survival at five years between women who received radiation and those who received no further treatment (Relative risk (RR) = 0.8, 95% Confidence interval (CI): 0.3 to 2.4). However, women who received radiation had a significantly lower risk of disease progression at five years (RR = 0.6, 95% CI 0.4 to 0.9).Although the risk of serious adverse events was consistently higher if women received radiotherapy rather than no further treatment, these increased risks were not statistically significant, probably because the rate of adverse events was low. AUTHORS' CONCLUSIONS: We found evidence, of moderate quality, that radiation decreases the risk of disease progression compared with no further treatment, but little evidence that it might improve overall survival. The evidence on serious adverse events was equivocal.

Differentiated-type vulval intraepithelial neoplasia has a high-risk association with vulval squamous cell carcinoma.

OBJECTIVE: To assess the potential malignant risk of vulval premalignant conditions, in particular, to investigate whether there is a difference in the cancer risk between women with the 2 types of vulval intraepithelial neoplasia (VIN). METHODS: All vulval biopsy specimens taken for any reason in a single center for a 5-year period were identified. The histologic reports of 1309 biopsy specimens from 802 women were reviewed, and all pathologic conditions present were recorded for each woman. Reports of patients with biopsy specimens containing usual-type VIN, differentiated-type VIN, lichen sclerosus, and squamous hyperplasia were selected and analyzed for the presence of metachronous or subsequent carcinoma to give a proportional risk for each condition. RESULTS: Five hundred eighty women were identified with premalignant vulval conditions: 171 had usual-type VIN, 70 had differentiated-type VIN, 191 had lichen sclerosus, 145 had squamous hyperplasia, and 3 had other conditions not included in this analysis. Within these groups, the numbers of women with prior, synchronous, or subsequent vulval squamous cell carcinoma were 44 (25.7%), 60 (85.7%), 53 (27.7%), and 53 (31.7%), respectively (P = 0.000). CONCLUSIONS: Differentiated-type VIN is significantly more associated with vulval squamous cell carcinoma than usual-type VIN.

Value of normal colposcopy after an abnormal cervical smear report.

BACKGROUND: Colposcopy is a secondary screening test used after a cytological specimen is reported as abnormal. A negative or normal colposcopy is not an infrequent outcome, and clinicians need to be aware of the clinical value of a normal and satisfactory colposcopic assessment.To address this problem, the underlying causes need to be fully understood. To this end, we have analyzed a retrospective dataset relating to new referrals to an urban colposcopy service. METHOD: We have reviewed 1,927 consecutive new colposcopic attendances during a 4-year period (1996-2000). Of these cases, 1,589 (82.4%) had documented satisfactory colposcopy in that the whole transformation zone was identified, and any lesion seen within it was suitable for outpatient-directed biopsy. These cases form the basis of this dataset. Seven hundred seventy-one colposcopies were classified as normal (48%). RESULTS: The presenting smear was atypical squamous cells of undetermined significance (ASCUS) (41.3%), high-grade squamous intraepithelial lesion (HiSIL) (42.2%), low-grade squamous intraepithelial lesion (LoSIL) (13.1%), and unsatisfactory in 3.4%. One hundred five patients (13.6%) eventually underwent loop diathermy excision (loop electrocautery excision procedure). The indications to treat were as follows: a high-grade smear (N=31; 29.5%), a colposcopic suspicion of any cervical intraepithelial neoplasia in the presence of any smear result (N=35; 33%), or a persisting minor cytological abnormality (N=39; 37%). Patients were treated either at their first visit if they had a high-grade smear or up to the 10th visit. Forty-eight (45%) of the treated patients had high-grade disease. No cases of invasive disease were recorded. CONCLUSION: Normal colposcopy in the presence of a low-grade cervical smear is associated with a very low risk of having or developing high-grade disease. The negative predictive value of normal colposcopy is a valuable clinical utility and underpins the importance of appropriate colposcopic training and the development of competencies that enable the confident exclusion of dysplasia.

Vaccines against cervical cancer.

PURPOSE OF REVIEW: The purpose of this review is to give an overview of recent developments relating to human papillomavirus vaccines and their effect on cervical cancer. Original research publications from the last year (2007) have been reviewed and summarized to present an up to date synopsis of relevant trials, and the impact they will have on clinical practice. Comparisons of the two vaccines on the market are made, and details of each are given. The effect of vaccination on men and those in the developing world is explored. RECENT FINDINGS: Recent findings include results of the Females United to Unilaterally Reduce Endo/Ectocervical Disease II (FUTURE II) and PApilloma TRIal against Cancer In young Adults (PATRICIA) trials that show a significant reduction in human papillomavirus-associated anogenital disease with both quadrivalent and bivalent vaccines. The effect is greatest in women who are not yet exposed to the human papillomavirus. The international community recognizes the potential impact of this, particularly in the developing world, and strategies are being developed to try and deliver care effectively. SUMMARY: In summary, research published in the last year has continued the initial optimistic outlook for human papillomavirus vaccination and it is likely that its effect on cervical cancer will be as promising as initially appeared.