Direct oral anticoagulants (DOACs) use for prolonged venous thromboembolism prophylaxis following surgery for gynaecological malignancies in Australia and New Zealand - A clinician survey.

BACKGROUND: Current international guidelines recommend 28 days of enoxaparin as venous thromboembolism (VTE) prophylaxis after surgery for gynaecologic cancer. Direct oral anticoagulants (DOACs) have been investigated as an alternative to enoxaparin for post-operative VTE prophylaxis. High-quality evidence to demonstrate safety and efficacy is lacking. AIMS: We aim to investigate the current practice regarding VTE prophylaxis among gynaecological oncologists in Australia and New Zealand following laparotomy for gynaecological malignancy, in particular the use of DOACs for VTE prophylaxis. MATERIALS AND METHODS: Sixty-seven practising gynaecologic oncologists (GO) were identified through Royal Australia and New Zealand College of Obstetricians and Gynaecologists database and emailed online surveys that asked about VTE prophylaxis practice and views of DOACs in this setting. Data were then collected through Survey Monkey and evaluated. RESULTS: The majority (77.1%) routinely prescribed 28 days of enoxaparin following laparotomy for gynaecological malignancies. In clinical circumstance such as laparoscopy for gynaecological malignancies and surgery for vulva malignancies, there was variation in thromboprophylaxis practices. No GO reported routine use of DOACs in any clinical circumstance. There were 56% of GOs who used a DOAC in their practice at some point. Barriers to routine use of DOACs in current practice included insufficient evidence (68%), issue with cost (40.4%) and concerns about safety (29.7%). CONCLUSIONS: Enoxaparin prescribed for 28 days remains the current clinical practice in preventing VTE following laparotomy for gynaecological malignancy. The main barrier to routine DOAC use as post-operative thromboprophylaxis is a lack of evidence which reflects the need for a larger prospective study.

Increasing incidence of endometrial cancer in Aotearoa New Zealand: Health professionals' perspective.

BACKGROUND: The incidence of endometrial cancer is globally increasing. Aotearoa New Zealand is no exception with a 59% increase in cases over that last ten years. AIMS: We report a sub-set of themes which pertain to provider reflections of rising endometrioid-type endometrial cancer incidence in individuals with high weight. MATERIALS AND METHODS: Fifteen semi-structured interviews with healthcare professionals experienced in providing care to women with endometrial cancer were audio-recorded and transcribed. Interviews were analysed using reflexive thematic analysis. RESULTS: Two main themes emerged: (1) concerns for the future; and (2) impact on fertility and treatment options. Healthcare professionals discussed rising incidence in younger people and a need for increased awareness about the association of excess weight as a risk factor for developing the disease. The concern extended to workforce and equipment shortfalls of meeting the needs of individuals with higher weight, which subsequently influenced treatment options, health outcomes and survivorship. CONCLUSIONS: Rising incidence of endometrial cancer in individuals with high weight presents multiple chances for inequitable access and health outcomes over the care continuum for endometrial cancer. Action is required to address incidence, awareness, access to equitable and inclusive treatment, and survivorship.

Predicting regression of cervical intraepithelial neoplasia grade 2 in women under 25 years.

BACKGROUND: A number of retrospective and prospective studies have documented substantial rates of regression in cervical intraepithelial neoplasia grade 2 lesions in young women. Initial observational management of cervical intraepithelial neoplasia grade 2 is increasingly accepted as appropriate for women under 25 years of age with screen-detected abnormalities and is included in a number of clinical guidelines. However, there has been a paucity of large prospective studies on observational management with strict inclusion criteria. A number of important questions remain, specifically regarding the clinical variables that are associated with the risk of progression or persistence of disease. To investigate these factors and to ensure that young women with cervical intraepithelial neoplasia grade 2 undergoing observational management were being managed in a well-monitored and an appropriately informed fashion, we conducted a large, multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 in women under 25 years. OBJECTIVE: This study aimed to determine the regression rates and clinical, cytologic, and pathologic predictors of regression of cervical intraepithelial neoplasia grade 2 in women under 25 years undergoing observational management over 24 months. STUDY DESIGN: This study was a multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 (ie, repeat colposcopy, cytology, and cervical biopsy every 6 months) for up to 24 months. A total of 615 consenting women under 25 years with newly-diagnosed, biopsy-proven cervical intraepithelial neoplasia grade 2 were recruited (from 2010 to 2016) through 16 hospital-based colposcopy units in New Zealand and Australia. RESULTS: At completion, 326 women had confirmed regression, 156 had persistent high-grade cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, and 24 had unconfirmed regression (ie, first regression at the 24-month follow-up). A total of 109 women did not complete the protocol (41 because of delayed follow-up, 41 lost to follow-up, 22 elected treatment, 4 refused a biopsy, and 1 died of an unrelated cause). Confirmed regression was observed in 53% (326 of 615) of all women enrolled in the study and, when missing data were imputed, it was estimated that 64% of women (95% confidence interval, 60%-68%) would have experienced regression. Similarly, lesions regressed in 64% (326 of 506) of women who completed the observational protocol. Based on a multivariable analysis, detection of human papillomavirus 16 in a liquid-based cytology sample at the time of initial colposcopy decreased the chance of regression by 31% (risk ratio, 0.69; 95% confidence interval, 0.56-0.86; P<.001). In addition, at initial colposcopy, low-grade or normal colposcopic impression, later year of diagnosis, low-grade or normal cytology, and being a nonsmoker were all independently associated with an increased chance of regression. CONCLUSION: More than half of women under 25 years with cervical intraepithelial neoplasia grade 2 will regress to cervical intraepithelial neoplasia grade 1 or normal within 24 months without destructive treatment. The absence of human papillomavirus 16 is the most important predictor of regression.

Use of direct oral anticoagulants for postoperative venous thromboembolism prophylaxis after surgery for gynecologic malignancies.

Venous thromboembolism is a preventable cause of postoperative mortality in patients undergoing surgery for malignancy. Current standard of care based on international guideline recommends 28 days of extended thromboprophylaxis after major abdominal and pelvic surgery for malignancies with unfractionated heparin or low molecular weight heparin. Direct oral anticoagulants have been approved for the treatment of venous thromboembolism in the general population. This regimen has a significant advantage over other types of anticoagulation regimens, particularly being administered by non-parenteral routes and without the need for laboratory monitoring. In this review, we evaluate the role of direct anticoagulation and provide an update on completed and ongoing clinical trials.

Excisional treatment comparison for in situ endocervical adenocarcinoma (EXCISE): A phase 2 pilot randomized controlled trial to compare histopathological margin status, specimen size and fragmentation after loop electrosurgical excision procedure and cold knife cone biopsy.

OBJECTIVE: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. We aimed to compare margins status, specimen size and fragmentation after loop electrosurgical excision procedure (LEEP) and 'cold knife cone biopsy' (CKC). METHODS: The EXCISE Trial was an investigator-initiated, multicenter, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. RESULTS: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p = 1·00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p = ·00). There were no differences in grade three complications (p = ·65). CONCLUSIONS: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardized protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted.

Evaluation of guidelines for observational management of cervical intraepithelial neoplasia 2 in young women.

BACKGROUND: A high rate of regression in young women with cervical intraepithelial neoplasia grade 2 has been recorded. However, there are few prospective data by which to evaluate management guidelines. OBJECTIVE: This study evaluates the American Society for Colposcopy and Cervical Pathology recommendations for follow-up of young women with cervical intraepithelial neoplasia 2 using data created by a large prospective multicenter study of observational management. MATERIALS AND METHODS: Participants were 616 women under 25 years with biopsy-diagnosed cervical intraepithelial neoplasia 2 following a referral to colposcopy for an abnormal smear with no previous high-grade abnormality. The protocol included colposcopy, cytology, and colposcopically directed biopsy at the initial visit and at 6- and 12-month follow-ups visits, and these data were analyzed. Histology from the corresponding cervical biopsy was treated as the reference diagnostic test. For young women with cervical intraepithelial neoplasia 2, we aimed to determine the following: (1) the ability of colposcopy to identify women with cervical intraepithelial neoplasia 3 or worse at 6 months; and (2) the ability of colposcopy, cytology, and a combination of cytology and colposcopy to identify residual high-grade abnormalities at 12 months. In addition, although not specified in the guidelines, we investigated the ability of high-risk human papillomavirus positivity alone or with cytology as a co-test to identify residual high-grade abnormalities at 12 months. RESULTS: At 6 months, cervical intraepithelial neoplasia 3+ colposcopic appearance identified only 28% (95% confidence interval, 18-40%) of women diagnosed with cervical intraepithelial neoplasia 3. At 12 months, a high-grade colposcopic appearance identified only 58% (95% confidence interval, 48-68%) of women with residual histological cervical intraepithelial neoplasia 2 or 3. At 12 months, high-grade cytology identified only 58% (95% confidence interval, 48-68%) of women with cervical intraepithelial neoplasia 2 or 3. However, the combination of either high-grade cytology or colposcopic appearance proved substantially more sensitive (81%; 95% confidence interval, 72-88%). High-risk human papillomavirus positivity at 12 months was a sensitive (96%; 95% confidence interval, 89-99%) indicator of persisting high-grade histology. However, this sensitivity came at the expense of specificity (52%; 95% confidence interval, 45-58%). A co-test of high-risk human papillomavirus positivity or high-grade cytology at 12 months provided a high sensitivity (97%; 95% confidence interval, 90-99%) but low specificity (51%; 95% confidence interval, 45%-58%). CONCLUSION: Colposcopy and cytology are limited in their ability to exclude persistent high-grade abnormality for young women undergoing observational management for cervical intraepithelial neoplasia 2. We recommend biopsy for all women at 12 months. High-risk human papillomavirus positivity is a sensitive indicator of persistent abnormality and should be considered in those not having a biopsy.

Low-grade serous ovarian carcinoma: A comprehensive literature review.

BACKGROUND: Low-grade serous ovarian carcinoma (LGSOC) is a unique entity with clinical and molecular characteristics distinct from high-grade serous ovarian carcinoma (HGSOC). To date the majority of research has focused on the more common HGSOC, with treatment recommendations often extrapolated to LGSOC. Women with LGSOC are typically diagnosed younger and have indolent and relatively chemoresistant disease. Recently there have been major research advances in LGSOC. AIMS: This systematic review describes the epidemiological, clinical and molecular characteristics of LGSOC, with advances in research and novel treatment options also discussed. MATERIALS AND METHODS: A 10-year comprehensive systematic review of peer-reviewed literature was conducted, with a total of 132 abstracts read, 89 articles reviewed and 49 included in this review. RESULTS: This review highlights the clinical and molecular features of LGSOC, current and traditional treatment options and areas of current research into targeted agents. CONCLUSIONS: Our growing knowledge about LGSOC as a distinct clinical and molecular entity from HGSOC has led to the investigation of more targeted and tailored therapies as their clinical course, optimal management and therapeutic targets differ. There is a need for ongoing collaborative research to provide better treatment options for these patients.

Pathological process has a crucial role in sentinel node biopsy for vulvar cancer.

OBJECTIVES: To report the interim findings of an audit of the outcomes of sentinel node (SN) biopsy performed as a replacement for groin node dissection in women with early stage vulvar cancer in routine clinical practice in Australia and New Zealand. METHODS: A prospective multi-center study in 8 participating centers. Eligible patients had squamous cell carcinomas clinically restricted to the vulva <4 cm in diameter. SN procedures and pathological assessment were to be performed in accordance with the methods published by the GROINSS-V collaboration [1]. RESULTS: 130 women with apparent early stage vulvar cancer were enrolled. Seventeen women subsequently did not meet the eligibility criteria and were excluded. SNs were identified in 111/113 of the remaining women. Twenty-two women had positive nodes. Sixteen of these women had at least 12 months follow up and 7 (44%) had recurrent disease. Eighty-nine women had only negative nodes. Seventy-four of these women had at least 12 months follow up and 6 (8%) had recurrent disease (including 2 [2.7%] with recurrence in the groin). On subsequent review of the two women with negative SNs who had groin recurrences, it was found that the recommended pathology protocol had not been followed. In both cases, SN metastases were identified following serial sectioning of the nodes. CONCLUSIONS: SN biopsy is feasible in routine clinical practice. However, undetected metastases in a removed SN may be associated with groin recurrence. To ensure patient safety, strict adherence to the pathology protocol is an essential component in the utilization of the sentinel lymph node technique in vulvar cancer.

Trends in the overall survival rates in women with advanced ovarian cancer in a single tertiary centre in New Zealand.

BACKGROUND: Survival rates for women diagnosed with ovarian cancer are much poorer than other gynaecological cancers and greatly depend on stage at diagnosis. A recent publication showed that unlike some other developed countries, there has been no improvement in the five-year survival rate for those diagnosed with ovarian cancer in New Zealand. AIM: To compare the five-year survival rate of women diagnosed with advanced ovarian cancer in a single tertiary hospital during two 36-month time periods 10 years apart. MATERIALS AND METHODS: An observational retrospective review of patient clinical notes, including all women diagnosed with stage three or four ovarian cancer between 2000 and 2002 (Cohort 1) and 2010-2012 (Cohort 2). Eligible patients were identified through the Regional Gynaecology Oncology database. Clinical notes were reviewed to compare the five-year survival rate between these two time periods and look at changes in patterns of care over time. RESULTS: Eighty-three women were diagnosed in 2000-2002 and 125 women in 2010-2012. There was no difference in five-year survival between cohorts (21.7% vs 23.2%, P = 0.80). Mean age at diagnosis did not differ between cohorts (62.1 years vs 63.5 years, P = 0.43); however, there were more women with stage four cancer in Cohort 2 (14% vs 30%, P = 0.01). In Cohort 2, more women were treated with neoadjuvant chemotherapy (20% vs 34%, P = 0.04) or chemotherapy only (6% vs 18%, P = 0.01). CONCLUSION: Five-year overall survival in women diagnosed with advanced ovarian cancer in our centre has not changed over the last 10 years.

Subtypes of stage IV ovarian cancer; response to treatment and patterns of disease recurrence.

BACKGROUND: To compare three different patterns of stage IV epithelial ovarian cancer; pleural effusion, parenchymal metastases and extra-abdominal lymph node metastases with treatment response and pattern of disease recurrence, and correlate treatment modality with outcome. METHODS: Retrospective analysis of FIGO stage IV epithelial ovarian cancer diagnosed between 2008 and 2012 in three gynaecologic oncology centres in New Zealand. RESULTS: 124 patients were analysed, 58 had pleural effusions, 38 parenchymal metastases, and 28 extra-abdominal lymph nodes. There was no significant difference in overall survival between these three groups. The most common site of first or any recurrence in all three groups was the abdomen with only a small number of recurrences arising in extra-abdominal sites. When looking at treatment modality, 13% had primary debulking surgery, 47% had neoadjuvant chemotherapy with interval debulking surgery, and 40% never had surgery. Overall survival was highest in patients with no residual abdominal disease after surgery. CONCLUSION: The site of extra-abdominal disease did not alter prognosis or pattern of disease recurrence in stage IV epithelial ovarian cancer, with most recurrences in the abdomen suggesting controlling abdominal disease with surgery may be important in all stage IV disease.

Initial observation of CIN2 does not appear to reduce quality of life in women under 25 years of age.

BACKGROUND: Although the patient perspective is implicit in the practice of medicine, research evaluating this remains scarce. In a climate where clinicians and policy-makers constantly strive to achieve more patient-centred models of care, this omission warrants attention. AIM: To assess health-related quality of life (HrQoL) in women under 25 years of age with cervical intra-epithelial neoplasia grade 2 (CIN2) receiving conservative management (colposcopy follow-up, with treatment if necessary) compared with those receiving immediate excisional treatment with large loop excision of the transformation zone (LLETZ). METHODS: An observational study evaluating HrQoL was conducted at Christchurch Women's Hospital, New Zealand. Women undergoing conservative management for CIN2 were compared with those undergoing immediate excisional treatment in an age-matched sample. The Short Form Health Survey 12 version 2 (SF-12v2) was used to evaluate HrQoL. Secondary outcomes of anxiety and sexual function were also assessed. RESULTS: One hundred and four women with CIN2 participated in the study. Of these, 63 (60%) received conservative management and 41 (40%) received immediate excisional treatment with LLETZ. We found no significant difference in HrQoL between the groups in a multivariate regression analysis adjusted for parity, smoking and socioeconomic status. There were also no significant differences in sexual function or anxiety. CONCLUSION: We found no difference in HrQoL by management strategy. Conservative management of CIN2 in women under 25 is unlikely to have an adverse impact on self-reported HrQoL, anxiety or sexual functioning compared with conventional management.

Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial.

Importance: Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective: To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants: The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions: Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures: The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results: Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, -5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, -3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, -3.0% to 4.2%]; P = .76). Conclusions and Relevance: Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration: clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.

Observational Management of CIN 2 in Young Women: A Prospective Multicenter Trial.

OBJECTIVES: We present the rationale and methods for PRINCess-a multicenter prospective trial-which aims to determine outcome and predictors of regression in a large cohort of women younger than 25 years with cervical intraepithelial neoplasia grade 2 (CIN 2) undergoing observational management. MATERIALS AND METHODS: Six hundred women younger than 25 years with newly diagnosed biopsy-proven CIN 2 are being recruited to observational management (i.e., repeat colposcopy, cytology, and cervical biopsy every 6 months for 2 years). Five hundred fifty-two women from throughout New Zealand and 1 site in Australia have been recruited so far. Measures include histology, cytology, human papillomavirus genotyping, and immunohistochemical staining. Women who develop CIN 3 will be treated with large loop excision of the transformation zone. The primary outcomes are rates of clinical regression of CIN 2 (i.e., 2 consecutive colposcopy follow-ups showing CIN 1 or normal), loss to follow-up, and progression to invasion. CONCLUSIONS: The optimal treatment for young women with a diagnosis of CIN 2 is controversial. Although many undergo surgical treatment, observational management is increasingly recommended. However, there is little evidence from large clinical trials of the safety and practicality of observational management of young women with CIN 2. When completed, we will have adequate evidence by which to counsel women regarding their likely outcomes and to offer advice on clinical follow-up protocols.

Recurrence of high-grade cervical abnormalities following conservative management of cervical intraepithelial neoplasia grade 2.

OBJECTIVE: Conservative management of cervical intraepithelial neoplasia (CIN) grade 2 in women younger than 25 years may reduce overtreatment. However, long-term efficacy remains uncertain. This retrospective cohort study aimed to determine the rate of recurrence of high-grade abnormalities among young women with a history of CIN 2 that spontaneously regressed within 2 years and compare this with the rate of high-grade abnormality in similar women with an initial diagnosis of CIN 1. STUDY DESIGN: We identified all women aged younger than 25 years who were diagnosed with CIN 1 or CIN 2 between January 2005 and August 2009 within 2 colposcopy units. Follow-up data from the National Cervical Screening Programme were obtained to identify those women who developed recurrent high-grade lesions before October 2012. Comparisons were made using Cox proportional hazards regression. RESULTS: A total of 683 women were included: 106 with CIN 2 that spontaneously regressed, 299 with treated CIN 2, and 278 with conservatively managed CIN 1. Median follow-up was 4 years. There was no significant difference in the risk of development of high-grade abnormalities after 2 years between the spontaneously regressing CIN 2 and CIN 1 groups (P = .83). Women with treated CIN 2 had a significantly lower risk of recurrence than women with untreated CIN 2 (P = .01). CONCLUSION: CIN 2 that has spontaneously regressed appears to behave as a low-grade lesion. This study contributes to the growing body of evidence that careful observation of CIN 2 is an efficacious and appropriate initial management option for women aged younger than 25 years at diagnosis.

The role of positron emission tomography/computed tomography in planning radiotherapy in endometrial cancer.

OBJECTIVE: The optimal method of assessing disease distribution in endometrial cancer is widely debated. Knowledge of disease distribution assists in planning adjuvant radiotherapy; in this study we used positron emission tomography/computed tomography (PET/CT) to assess disease distribution before radiotherapy. METHODS: Seventy-three consecutive patients referred to the Peter MacCallum Cancer Centre for adjuvant radiotherapy for endometrial cancer, with either high-risk disease after a hysterectomy or recurrent disease, had a PET/CT before treatment. The findings on PET/CT and clinical course were recorded. RESULTS: PET/CT found additional disease in 35% of postoperative patients, changing planned treatment in 31%. In the group with known recurrence, additional disease was found in 72%, changing management in 36%. CONCLUSIONS: PET/CT is a valuable tool for planning radiotherapy in endometrial cancer.

Exploring health professionals' viewpoint of provision of nutrition advice for women with endometrial cancer.

AIMS: The aim of this study was to explore barriers and facilitators to delivery and uptake of nutrition advice to women diagnosed with endometrial cancer from a health professionals' viewpoint. METHODS: Fifteen semi-structured interviews with health professionals with experience in providing healthcare to women diagnosed with endometrial cancer were audio-recorded and transcribed. Interviews were analysed using reflexive thematic analysis. Topics included high weight as a risk factor for endometrial cancer, nutrition information sources, and barriers and facilitators to delivering nutrition advice in clinical care. RESULTS: Four themes were identified. The first three exist as barriers to women receiving nutrition advice-how to navigate conversations about high weight, access to limited resourcing and health professionals feeling powerless to overcome system influences. The fourth theme identified a community approach need to facilitate a supportive environment and share knowledge. CONCLUSIONS: This study, through the lens of health professionals, highlights barriers to the delivery and uptake of nutrition advice at the patient, community and system levels. Enhancing survivorship for women after the diagnosis of endometrial cancer may be enabled by further understanding of how to overcome barriers and promote facilitators. Communication and partnership with women are imperative to achieving this.

Endometrial cancer diagnoses prompted by routine cervical cytology: a retrospective case study.

AIMS: Endometrial cancer is the commonest gynaecological cancer in New Zealand. Some women have their diagnosis of endometrial cancer prompted by an abnormal cervical cytology screening test. When high-risk human papillomavirus (hr-HPV) testing becomes the primary test for cervical screening, this avenue of incidental diagnosis will be reduced. Therefore, our aims were to estimate the proportion of women whose diagnosis of endometrial cancer follows incidental detection on routine cervical cytology, and to understand the clinicopathologic characteristics of these cases. METHODS: Retrospective analysis of patient medical records from women of cervical screening age diagnosed with endometrial cancer between 2015-2019 in the South Island of New Zealand. RESULTS: Of 334 women, 26 (7.8%) had endometrial cancer diagnosis prompted by abnormal cervical cytology. Most women had low-grade (17/26, 65.4%), low-stage (18/26, 69.2%) disease of endometrioid histologic subtype (21/26, 80.8%). The small cohort prevented significant correlations with clinicopathologic characteristics and outcomes. Overall, cervical cytology had low sensitivity (32.3%) for the detection of endometrial cancer in the 6 months before diagnosis. CONCLUSIONS: A small number of women currently have diagnoses of endometrial cancer prompted by routine cervical screening with cytology. However, the undefined clinical benefit from and poor sensitivity of cervical cytology for detecting endometrial cancer does not justify its use in screening, or opposition to hr-HPV cervical screening.

The High-Risk Human Papillomavirus Type Influences the Tissue Microenvironment in Cervical Intraepithelial Neoplasia Grade 2.

High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial neoplasia grade 2 lesions differed from other high-risk types (HPV 'other'). Consistent with other studies, we found that progression to higher-grade disease was more frequent in HPV16/18 lesions when compared with HPV 'other' lesions. HPV16/18 lesions were significantly more likely to be indoleamine 2,3,-dioxygenase 1 (IDO1)-positive and were associated with reduced CD8 and FoxP3 T cells in the lesion. In the stroma, reduced Tbet- and CD32-positive cells and increased Blimp1-positive cells were significantly associated with HPV16/18 lesions when compared with HPV 'other' types. On analysis of the IDO1-positive tissues, lesional IDO1 was associated with significantly decreased numbers of CD4-, CD8-, and FoxP3-positive cells in the stroma compared with IDO1-negative tissues. These data suggest that IDO1 expression may impair infiltration of CD4, CD8, and FoxP3 cells into the stroma beneath the precancer lesion. Increased expression of IDO1 may contribute to immune avoidance and an increased frequency of disease progression in HPV16- and 18-positive lesions.

Blimp-1 is a prognostic indicator for progression of cervical intraepithelial neoplasia grade 2.

BACKGROUND: Progression of cervical intraepithelial neoplasia (CIN) to higher grade disease is associated with persistent human papillomavirus (HPV) infection and an absence of immune-mediated regression. However, the immune microenvironment that distinguishes progression from persistent or regressing lesions has not been well defined. METHODS: A total of 69 patients under the age of 25 with high-risk HPV-positive cytology and biopsy-confirmed p16-positive CIN2 were included in the study. Biopsies were stained using 20 antibodies to a range of immune markers. Based on a 2-year follow-up, samples were analysed in "progressor" (CIN3 +) or "persister/regressor" (CIN1, 2 or normal) groups. RESULTS: Progression was most strongly associated with Blimp-1 positive cell staining in the lesion (P = 0.0019) and with low numbers of infiltrating CD4 cells in the dermal region beneath the lesion (P = 0.0022). The presence of CD4, CD8 and T bet-positive cells in the dermal region most strongly correlated with CD11c cells in the persister/regressor but not the progressor group. CONCLUSION: High numbers of Blimp-1 + cells in CIN2 lesions may predict progression to more severe disease. Measurement of Blimp-1 may have diagnostic utility for the determination of the need to treat women with cervical pre-cancer. HIGHLIGHTS: CIN2 progression is associated with high numbers of Blimp-1 positive cells in the lesion. Detection of Blimp-1 in the lesion may have utility as a prognostic test to inform the need to treat CIN2.