Vulvar and Vaginal Graft Versus Host Disease After Allogeneic Stem Cell Transplant-A Systematic Review.

OBJECTIVE: To conduct a systematic literature search to identify and determine the prevalence, signs and symptoms, and clinical management of vulvar and vaginal graft versus host disease (GVHD). METHODS: A systematic literature search of articles from 1993 to August 2022 was performed. Studies were included if full text was available in the English language and provided reports on female subjects with more than four patients. Review articles, conference abstracts, case reports, and case series of less than 5 patients were excluded. Included studies had their reference list searched for further manuscripts. Two authors reviewed the search results and independently identified studies that met the selection criteria and summarized available data. RESULTS: There were 29 studies available in the literature that met the inclusion criteria. There was a high risk of bias within the available literature. The prevalence of vulval and vaginal GVHD varied between 27% and 66% of women after allogeneic stem cell transplant. Other organ GVHD, most commonly the skin, mouth, and eyes, may be present concurrently in these patients, or they may be asymptomatic. Specialist gynecology review, topical estrogen, topical steroids, topical immunosuppression, and vaginal dilatation led to a reduction in complications associated with the condition, and surgery was helpful in some severe refractory cases. These patients remain at higher risk of developing cervical dysplasia, and regular human papillomavirus screening is recommended. CONCLUSIONS: Female genital GVHD is a rare phenomenon. Early, coordinated, and regular gynecological reviews after stem cell transplant are essential to reduce the long-term complications.

Voluntary assisted dying in gynaecological cancers: A discussion of the history, ethical principles and international perspectives.

Voluntary assisted dying (VAD) is a provocative and ethically charged subject that will potentially be an increasing component of our clinical practice. This paper aims to give the history of VAD, ethical principles, controversies and international perspectives regarding the laws in each jurisdiction. It provides a discussion on the topic with respect to gynaecological oncology to enable clinicians to feel more comfortable with this difficult subject.

Primary HPV cervical screening: Clinical audit of outcomes of women seen at a tertiary referral centre for colposcopy in Australia.

BACKGROUND: Primary human papillomavirus (HPV) screening was introduced in Australia in December 2017. AIMS: Outcomes for women after positive HPV in their cervical screening test (CST). MATERIALS AND METHODS: A retrospective observational study of 4458 women seen at the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020. RESULTS: HPV16/18 was positive (considered higher-risk CST) in 42.2% of women in the study, 16.6% with reflex possible with high-grade squamous intraepithelial lesions (pHSIL) or worse and 54.9% with normal cytology. There were 24.8% of women with positive HPV16/18 who had histological confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+), 10.3% CIN2+ (including six cancers) among women with reflex negative cytology and 87.7% CIN2+ among women with reflex HSIL cytology. In women with positive HPV (not 16/18), CIN2+ was found in 60.2% with reflex pHSIL or worse cytology (higher risk) and 10.2% with reflex low-grade SIL (LSIL) or normal cytology (intermediate risk). Median waiting time to colposcopy with the intermediate-risk group went up to 181 days. Our colposcopists were able to achieve a positive predictive value (PPV) for CIN2+ of 69.9%, higher than 57.8% PPV in the National Cervical Screening Program (NCSP) 2020 monitoring report. Women with type 3 transformation zone on colposcopy could be followed up with CST if no HSIL was suspected on screening or at colposcopy as their risk of CIN2+ was only 2.5%. CONCLUSIONS: Our findings support direct referral to colposcopy for women with higher-risk CST, with all cancers confined to this group. The NCSP recommendation to refer for colposcopy only after three intermediate-risk CST will need monitoring with the LSIL triage group.

Prognostic value of serum HE4 level in the management of endometrial cancer: A pilot study.

BACKGROUND: Human epididymis protein 4 (HE4) has shown promising utility as a prognostic biomarker in endometrial cancer. Increased serum HE4 levels may be associated with deeper myometrial invasion, extrauterine disease and poorer prognosis. AIM: To evaluate the use of serum HE4 level, compared to and alongside other investigations, to accurately guide management in apparent early-stage endometrial cancer. MATERIALS AND METHODS: This is a single-site prospective study of 100 patients with histologically confirmed endometrial cancer. All patients underwent preoperative measurements of HE4 and CA125 levels and a preoperative magnetic resonance imaging (MRI) to assess the depth of invasion, nodal status and tumour size. Correlation was sought between serum HE4 level, CA125 level, MRI findings and intra-operative frozen section with tumour type, grade and stage. RESULTS: While both median HE4 and CA125 levels were higher with worsening clinicopathological features, serum HE4 level showed a more consistent association with high-risk features. Patients with a low-grade biopsy preoperatively and a low HE4 level (<70 pmol/L) demonstrated an 86.8% likelihood of having low-risk disease on final histopathology. In comparison, preoperative MRI or intraoperative frozen section alongside a low-grade biopsy demonstrated a similar likelihood of 86.2 and 87.7%, respectively. CONCLUSIONS: When used in conjunction with an initial low-grade endometrial biopsy, serum HE4 level demonstrated a similar likelihood to both preoperative MRI and intraoperative frozen section in identifying low-risk disease on final histopathology. As a triaging tool this may be significant given that a preoperative, serum-based assay would likely be the least invasive, least resource-intensive and most cost-effective approach.

Advances in epithelial ovarian cancer.

BACKGROUND: Most epithelial ovarian cancer occurs in older women, with a mean age at diagnosis of 62 years and an overall five­year survival rate in Australia of 43%. Most women are diagnosed with advanced disease of high-grade serous type with 20-30% five-year survival; 70% relapse within three years of initial treatment. There is no available screening test for ovarian cancer. OBJECTIVE: The aim of this article is to highlight current management and future directions for women diagnosed with epithelial ovarian cancer, particularly the high incidence of underlying genetic mutations and new options for treatment. DISCUSSION: Risk-reducing surgery with bilateral salpingo-oophorectomy is recommended for women at high risk of developing ovarian cancer. Ovarian cancer treatment still centres on surgery and chemotherapy, with aggressive cytoreductive techniques and intraperitoneal treatments being evaluated in advanced disease. Molecular targeting agents are revolutionising treatment options, particularly the poly adenosine diphosphate-ribose polymerase inhibitors, and especially for patients with an underlying BRCA mutation. Other molecular targeting agents, such as vascular endothelial growth factor (VEGF) receptor inhibitors and newer approaches using immunotherapy and molecular targeting, aim to individualise treatment and improve survival in the future.

Menopausal hormonal therapy in gynaecological cancers: An evidence-based approach for clinical management.

Treatment for gynaecological malignancies often requires oophorectomy or loss of ovarian function from adjuvant treatment. Premature or early menopause caused by gynaecological cancer treatment may require menopausal hormonal therapy (MHT) to treat vasomotor symptoms. However, concerns exist due to theoretical risks of stimulation of hormonal-sensitive tumours and hence increasing recurrence risk. There are small numbers of often underpowered fair to poor quality studies indicating that MHT is safe with most gynaecological malignancies. These studies are of variable quality with most being retrospective. We present the available data on this subject relative to the common types of gynaecological cancer.

Patient symptom experience prior to a diagnosis of oesophageal or gastric cancer: a multi-methods study.

BACKGROUND: Late stage diagnosis of oesophageal and gastric cancer is common, which limits treatment options and contributes to poor survival. AIM: To explore patients' understanding, experience and presentation of symptoms before a diagnosis of oesophageal or gastric cancer. DESIGN & SETTING: Between May 2016 and October 2017, all patients newly diagnosed with oesophageal or gastric cancer were identified at weekly multidisciplinary team meetings at two large hospitals in England. A total of 321 patients were invited to participate in a survey and secondary care medical record review; 127 (40%) participants responded (102 patients had oesophageal cancer and 25 had gastric cancer). Of these, 26 participated in an additional face-to-face interview. METHOD: Survey and medical record data were analysed descriptively. Interviews were analysed using thematic analysis, informed by the Model of Pathways to Treatment. RESULTS: Participants experienced multiple symptoms before diagnosis. The most common symptom associated with oesophageal cancer was dysphagia (n = 66, 65%); for gastric cancer, fatigue or tiredness (n = 20, 80%) was the most common symptom. Understanding of heartburn, reflux and indigestion, and associated symptoms differed between participants and often contrasted with clinical perspectives. Bodily changes attributed to personal and/or lifestyle factors were self-managed, with presentation to primary care prompted when symptoms persisted, worsened, or impacted daily life, or were notably severe or unusual. Participants rarely presented all symptoms at the initial consultation. CONCLUSION: The patient interval may be lengthened by misinterpretation of key terms, such as heartburn, or misattribution or non-recognition of important bodily changes. Clearly defined symptom awareness messages may encourage earlier help-seeking, while eliciting symptom experience and meanings in primary care consultations could prompt earlier referral and diagnosis.

A retrospective observational study for the outcomes of women presenting to a colposcopy clinic with a high-grade Pap smear - Implications for a 'see and treat' approach to management.

BACKGROUND: The current Australian National Health and Medical Research Council guidelines discourage the use of 'see and treat' colposcopic management due to concerns regarding over-treatment. However, this approach has been shown to have benefits in several studies, including cost savings, elimination of loss to follow up and decreased patient anxiety. AIMS: To provide Australian data on treatment outcomes for women presenting with a high-grade Pap smear to a large metropolitan colposcopy unit and to determine whether a 'see and treat' approach would meet specified standards. MATERIALS AND METHODS: Retrospective review of women referred to the Royal Prince Alfred Hospital colposcopy unit with a high-grade smear. Patient data, colposcopy findings, treatment and pathology results were collated and analysed to determine treatment outcomes using the current 'biopsy and treat' approach. The feasibility of 'see and treat' was assessed by determining which women with high-grade colposcopy findings had high-grade disease confirmed on biopsy or excisional specimens. RESULTS: One hundred and thirty-seven women underwent either excisional or ablative treatment. Of those undergoing excisional procedures, 81.3% had high-grade dysplasia or invasive cancer, 11.6% had CIN1 and 7.1% had no dysplasia on histopathology. One hundred and twenty-one with high-grade colposcopy findings had histopathology results available. Using a 'see and treat' approach, 92.6% would have had confirmed dysplasia of any grade, while 91.7% had confirmed high-grade dysplasia. CONCLUSIONS: 'See and treat' colposcopy is feasible in the Australian setting when applied to selected patients with high-grade cytology and high-grade colposcopic findings.

HE4, CA125, the Risk of Malignancy Algorithm and the Risk of Malignancy Index and complex pelvic masses - a prospective comparison in the pre-operative evaluation of pelvic masses in an Australian population.

BACKGROUND: Human epididymis protein 4 (HE4) has been proposed as a novel biomarker for the diagnosis of epithelial ovarian cancer. Using HE4 and CA125, the risk of malignancy algorithm (ROMA) has been shown to be effective in the stratification of epithelial ovarian cancer risk. AIMS: To determine the effectiveness of HE4 and ROMA in the diagnosis of malignancy of women presenting with a complex pelvic mass in an Australian population and to compare it with CA125 and the risk of malignancy index (RMI). MATERIALS AND METHODS: Prospective recruitment of women was conducted between October 2012 and March 2014 (n = 50). CA125 and HE4 serum concentrations were collected and stored for subsequent analysis. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) were calculated for HE4, CA125, ROMA and the RMI. Receiver operating characteristic (ROC) area under the curves (AUC) were also calculated for comparison. RESULTS: There was a higher HE4 level in women with ovarian cancer compared with women with benign pathology (P = 0.008), and this observation was seen in benign versus stage 1 ovarian cancer women (P = 0.025). HE4 had a better specificity than CA125 for the diagnosis of ovarian cancer in all women (P = 0.022), and this effect was also observed in premenopausal women (P = 0.012). Furthermore, the ROC-AUC for HE4 was superior than CA125 in all women (P = 0.0451). The ROMA algorithm was not inferior to the RMI calculation in this population. CONCLUSIONS: In an Australian population, HE4 and ROMA are useful in the diagnosis of epithelial ovarian cancer.

Abnormal cervicovaginal cytology, unsatisfactory colposcopy and the use of vaginal estrogen cream: an observational study of clinical outcomes for women in low estrogen states.

AIM: To determine the effectiveness of vaginal estrogen cream to improve the rate of satisfactory colposcopy and subsequent smear result in patients in a hypoestrogenic state and an abnormal Papanicolaou smear. To delineate between abnormal smears secondary to atrophy and inflammation from preneoplastic change and suggest an effective treatment strategy to deal with this challenging situation. METHODS: Patients with abnormal cervicovaginal smears who were in a low estrogen state (postmenopausal or amenorrheic postnatal) undergoing colposcopy were identified. All patients had an unsatisfactory colposcopy and were treated with vaginal estrogen cream twice per week for 6 weeks and underwent repeat colposcopy, smear and targeted biopsy where required. RESULTS: Fifty-four patients had an abnormal smear and were clinically in a low estrogen state, with four having previously had a hysterectomy. After 6 weeks of vaginal estrogen therapy, 32 out of 50 patients' colposcopic examinations were satisfactory. Also, 40 out of 54 patients' smears returned to normal after treatment. Of the 14 patients with persistent smear abnormalities, only three were diagnosed with true high-grade pre-invasive disease. CONCLUSION: The use of vaginal estrogen cream for patients with smear abnormalities and a low estrogen status improves the satisfactory colposcopy rate and improves the accuracy of the prediction of true high-grade pre-invasive disease. This treatment may then reduce the number of patients that require definitive treatment for their screen-detected abnormalities in this patient population.