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ObjectivesWe report the disease-specific survival of patients with human papillomavirus (HPV)-associated and HPV-independent vulvar squamous cell carcinomas and determine whether differences exist and are independent of stage and age at diagnosis.MethodsThis was a retrospective cohort study with case note and pathology slide review of 265 consecutive women with vulvar squamous cell carcinoma. These patients were treated over a 15 year period (2001–2016) at a centralized cancer center covering half the population of New Zealand. The women’s cancers were categorized dependent on their adjacent pathology, immunohistochemistry and HPV status following expert slide review. Disease-specific survival was calculated using Kaplan-Meier univariable and Cox proportional hazard (adjusting for stage, age, and HPV dependence) multivariable methods.ResultsThe survival analysis included 236 women with follow-up to 96 months; 124 of them were HPV-associated, 95 HPV-independent, and 17 were unclassifiable. Of the 236 women, 146 were stage 1 (92 HPV-associated, 49 HPV-independent, 5 unclassifiable), 13 stage II (7 HPV-associated, 6 HPV-independent), 62 stage III (20 HPV-associated, 34 HPV-independent, 8 unclassifiable) and 15 stage IV (5 HPV-associated, 6 HPV-independent, 4 unclassifiable). HPV-independent vulvar squamous cell carcinomas had significantly worse survival than HPV-associated vulvar squamous cell carcinomas independent of stage and age at diagnosis (HR 3.6 (95% confidence interval (CI): 1.6 to 8.2)). Tumors that were unclassifiable by HPV type also had significantly worse survival than HPV-associated tumors independent of stage and age at diagnosis (HR 6.2 (95% CI: 2.4 to 16.0)).ConclusionsHPV-independent vulvar squamous cell carcinomas present more frequently in older women than HPV-associated tumors. However, the poorer prognosis is independent of age and stage, with worse outcomes even in early stage disease.

Objective Enhanced recovery after surgery (ERAS) programs fast-track recovery for surgical procedures, including colorectal and gynecological oncology surgery. Early mobilization is a postoperative ERAS module that can be self-managed by patients, but poor adherence is common. Visualization is increasingly being used to improve patient understanding and adherence to health behaviors. This study tested whether an animated visualization intervention could improve adherence to postoperative mobilization. Method Ninety six colorectal and gynecological oncology surgery patients were randomized to intervention, active control, or standard care groups. Intervention participants saw an animated intervention on a computer tablet at Day 1 postsurgery. All participants wore fitness trackers from day of discharge to 7 days postdischarge, and completed psychological measures at baseline, Day 1 postsurgery, and 7 days postdischarge. Results Step count data was available for 57 colorectal surgery participants. A main effect of group demonstrated that intervention participants had a significantly higher average daily step count from discharge across the week following discharge (Madj = 2,294.60, 95% confidence interval [CI] [1,746.11, 2,744.89]) compared with control participants (Madj = 1,347.25, 95% CI [826.51, 1,871.20]; p = .05). At postsurgery, intervention participants reported significantly greater perceived quality of recovery and less difficulty in being mobile compared with control participants. There were no between-group differences in self-reported exercise or perceptions of surgery and recovery. Conclusion This brief intervention appears effective in improving perceptions of early mobilization, and initial evidence suggests improvements in adherence to postsurgical mobilization. This intervention has high clinical applicability and could be incorporated into postoperative standard care. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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.A prospective multi-center study in 8 participating centers. Eligible patients had squamous cell carcinomas clinically restricted to the vulva4 cm in diameter. SN procedures and pathological assessment were to be performed in accordance with the methods published by the GROINSS-V collaboration [1].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.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.

Background Germline BRCA1/2 mutations account for approximately 15% of invasive ovarian carcinomas. Referral of all women with non-mucinous epithelial tubo-ovarian and peritoneal cancer, especially high-grade serous carcinoma (HGSC) to genetic services for genetic counselling and subsequent BRCA testing, has become standard of care in many countries. Publicly funded BRCA testing was restricted to women ≤70 years old with HGSC in New Zealand for most of our study period. Referral rates of women with HGSC for BRCA mutation testing in New Zealand have not previously been reported. Aims To determine the proportion of eligible patients with tubo-ovarian or peritoneal HGSC referred to Auckland Gynaecologic Oncology Centre who were referred for genetic counselling. To determine the number of patients who underwent BRCA1/2 genetic testing and the rate of germline BRCA mutations. Methods Eligible cases were identified from Auckland Gynaecologic Oncology multidisciplinary meetings database from 1 January 2012 to 31 December 2014. Genetic referrals sent were checked against the genetic services database to ensure that referrals were received. Genetic counselling clinic attendance, uptake and results of genetic testing were also collected. Results One hundred and four eligible patients were identified with 58 patients referred. Referral rates increased from 37.5% in 2012 to 64.3% in 2014. Of the 58 patients referred, 53 attended genetic counselling, and 49 underwent BRCA mutation testing, of whom 10 (20.4%) tested positive for a germline BRCA mutation. Conclusion Overall, 55.8% of eligible patients were referred for genetic testing; however, referral rates increased with time. This BRCA mutation-positive rate is comparable with current international data.

A 47- year-old woman developed a rapidly enlarging vulvar mass. Although the clinical appearance suggested malignancy, its lack of atypia and invasion on initial superficial biopsy delayed the pathological diagnosis. It was not until a large incisional biopsy was performed that showed the diagnosis of verrucous squamous cell carcinoma (VSCC) involving pre-existing sinuses of hidradenitis suppurativa (HS). VSCC arising in HS is very rare and often leads to death in published cases. This case demonstrates the challenge in pathological diagnosis of this condition which impacted time to treatment.

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.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.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.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.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.

Background/objectives: Vulval lichen sclerosus (VLS) is a chronic inflammatory skin condition predominantly affecting the anogenital region in women and children. To date, there is lack of agreement amongst experts on a severity scale to aid assessment, research and treatment stratification on VLS. Furthermore, literature on best practice for long-term management of VLS is lacking. The aim of this consensus is to provide broad guidelines on the short and long-term management of VLS. Methods: An initial focus group of Australasian experts in vulval dermatology developed a draft consensus statement for the management of VLS. Based on the results of the draft statement, a consensus panel of 22 Australasian experts, comprised of the initial and additional members, participated in an anonymous four-stage eDelphi process. Round 1 involved generation and voting on statements from the draft consensus statement developed by the focus group. In Rounds 2, 3 & 4, panel members were presented formal feedback from previous rounds and asked to indicate their level of agreement. Consensus was reached if there was ≥70% agreement on the importance of an item in the 4 (agree) to 5 (strongly agree) range. Results: The expert panel, with a total of 504 collective years of experience in the field of VLS, reached consensus on a core set of 51 management statements related to diagnosis, severity, initial and long-term management, follow-up, and complications of VLS. Conclusions: This study has identified a set of management statements for VLS that may be useful in clinical practice in the Australasian population.

Most cervical cancers are associated with human papillomavirus (HPV) types 16 and 18. In 2008, New Zealand commenced a quadrivalent HPV (virus-like particles of types 6, 11, 16 and 18) vaccination programme.Document trends in number of colposcopy referrals and number and grade of cervical abnormalities diagnosed in women (20-24 years) referred to three large colposcopy clinics over time.Retrospective analysis of colposcopy clinic data.The dataset included 5,012 episodes from 4,682 women. In Auckland (2013-2017), there was a 38% decrease in colposcopy referrals and 55% decrease in cervical intraepithelial neoplasia grade 2 (CIN2) or worse diagnoses. In Waikato (2011-2017), there was an 8% decrease in referrals and 22% reduction in CIN2 or worse diagnoses. In Canterbury (2011-2017), there was a 24% decrease in referrals and 49% reduction in CIN2 or worse diagnoses. Across all centres, the decrease in cervical intraepithelial neoplasia grade 3 (CIN3) or worse diagnoses was marked and more consistent than in CIN2 diagnoses. However, while the proportion of biopsies reported as CIN3 or worse decreased in non-Māori (24% in 2013 vs 16% in 2017, nptrend z=-4.24, p|z|.001), there was no change in Māori women (31% in 2013 vs 29% in 2017, nptrend z=-0.12, p|z| =.90).We observed a decreased number of CIN diagnoses in young women over time, with a particularly large drop in the number of CIN3/AIS/CGIN diagnoses. However, compared to non-Māori, Māori women having biopsies are more likely to have CIN3 or worse and there was a smaller reduction in the total number of Māori women diagnosed with CIN2 or worse.

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.

Vulval lichen sclerosus is an inflammatory genital skin condition associated with poor quality of life, sexual dysfunction and risk of squamous cell carcinoma. The aim of this study was to document the demographics of women with lichen sclerosus seen at specialist vulval clinics.We performed a retrospective review of women with lichen sclerosus seen at a tertiary combined gynaecology/dermatology vulval clinic over 12 months and Auckland Regional sexual health vulval clinics over five years. Data were collected for age, ethnicity, skin biopsy, treatment, referral source and time from symptom onset to diagnosis. Ethnicity was compared with Census data for the Auckland region.Three hundred and thirty-five women were included; 273 from the gynaecology/dermatology clinic and 62 from sexual health. Women seen at sexual health were younger than those seen by gynaecology/dermatology (mean age 45 and 64, respectively; p0.0001). Most referrals were from general practitioners (54%), although self-referrals made up 42% of sexual health consultations. The most common ethnicity was European (82%) followed by Asian (10%), Māori (4%) and Pacific Peoples (3%). Compared with Census data, European women were over-represented and Māori, Pacific and Asian women were under-represented.We found inequitable ethnic representation of women with vulval lichen sclerosus seen at our institution. Causes may include sociocultural beliefs, variations in access to care or ethnic differences in the prevalence of lichen sclerosus. A deeper understanding of underlying issues would enable planning of initiatives to ensure equitable access to specialist care for all New Zealand women with vulval conditions.

The authors regret that Donal Brennan was missing from the author list. The details shown above are now correct with Dr Brennan included. Dr. Brennan contributed to conceptualisation and data curation and final review of manuscript. Dr. Brennan does not have any conflicts to disclose. The authors would like to apologise for any inconvenience caused.

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.

Background: 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. Two common procedures are loop electrosurgical excision procedure (LEEP) and ‘cold knife cone biopsy’ (CKC), yet no randomised trials have compared these modalities. We aimed to compare margins status, specimen size and fragmentation after LEEP and CKC. Methods: The EXCISE Trial was an investigator-initiated, multicentre, open-label, parallel-group, phase 2, randomised 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 by computer generated random numbers. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. Findings: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. All patients were included in the analysis. 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). Interpretation: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardised 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. Trial Registration: The study is registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR registration number ACTRN12617000132347). Funding Statement: Australia New Zealand Gynaecological Oncology Group [#FNR2016/03]. Declaration of Interests: PAC and CDHW have received honoraria from Seqirus unrelated to this work. All other authors declare no competing interests. Ethics Approval Statement: Ethical approval for the study was granted by the St John of God Healthcare Human Research Ethics Committee (Reference number #1137) and approvals were obtained at all participating sites.

Objective To investigate the incidence and survival of Vulvar Squamous Cell Carcinoma (VSCC) by etiology over a 27 year period. Method Retrospective case-note and pathology slide review of 390 consecutive VSCC, treated at a Centralized Cancer Centre covering half New Zealand's population, 1990–2016. Incidence was calculated in 5–6 year cohorts and correlated with precursor of the VSCC, age and stage. Results Age-standardized incidence of all VSCC did not change significantly, however age standardized incidence of HPV-dependent VSCC increased significantly, from 0.55/100,000 (95% CI 0.38–0.72) in 1991–2000 to 0.83/100,000 (95% CI 0.68–0.97) in 2001–2016, with a significant decrease in the incidence of HPV-independent VSCC, from 0.76/100,000 (95% CI 0.58–0.95) to 0.54/100,000 (95%CI 0.43–0.65). HPV-dependent VSCC in women ≥50 years increased significantly from 0.75/100,000 (95% CI 0.45–1.17) to 1.43/100,000 (95% CI 1.14–1.77), with no significant change seen in younger women. HPV-independent VSCC in women ≥50 years has decreased significantly from 2.53/100,000 (95% CI 1.95–3.23) to 1.62/100,000 (95% CI 1.31–1.98) with no change in younger women. The proportion of HPV-dependent VSCC has increased from 25% to 50%. Age standardized death rate from VSCC has not changed significantly from 0.22/100,000 (95% CI 0.10–0.34) in 2001–5 to 0.27/100,000 (95% CI 0.15–0.40) in 2011–16. Five year survival for HPV-dependent VSCC was 93% and 68% for HPV-independent VSCC (p Conclusions HPV-dependent VSCC incidence has increased significantly and now accounts for half of VSCC, with a significant rise in women over 50. HPV-dependent and independent VSCC have different prognoses and should be registered and investigated separately.

Background A high rate of regression in young women with cervical intraepithelial neoplasia grade 2 has been recorded. However, there is little 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 multicentre study of observational management. Study Design 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 analysed. 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; (1) the ability of colposcopy to identify women with cervical intraepithelial neoplasia 3 or worse at 6 months and (2) the ability of a) colposcopy, b) cytology, and c) the 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 only identified 58% (95% confidence interval 48, 68%) of women with residual histological cervical intraepithelial neoplasia 2 or 3. At 12 months, high grade cytology only identified 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.

Background: Endometrial carcinoma (EC) is increasing in incidence, attributed largely to the obesity epidemic. Ethnic differences in New Zealand have long been recognised, with Pacific women bearing the greater burden of disease. We hypothesise that the pooled national incidence rates underestimate the true burden of EC in our high‐risk community. Aims: We aimed to: (1) determine the incidence, trends and outcome of EC in the high‐risk community served by our hospital, relative to national data; and (2) examine associated demographic, and clinicopathological features with reference to risk factors, to identify potential clinical and population intervention points. Materials and Methods: All area‐resident women treated for EC at Middlemore Hospital from 2000 to 2014 were identified from records, and clinicopathological data obtained. Incidence and time trend analyses were performed with reference to tumour type, age and ethnicity. Results: The study included 588 women. Pacific, followed by Māori, women had the highest incidence of EC (relative risk = 5.11 and 2.47, respectively, relative to ‘Other’ women). The incidence increased for all ethnicities (annual percentage change (APC) of 7.3; 95% CI 3.6–11.1), most marked in women aged below 50 years (APC of 12.2; 95% CI 5.2–19.7). This occurred predominantly in Pacific women, who had a high prevalence of potentially reversible risk factors. Disease‐specific survival was worse in Pacific, and to a lesser extent, Māori women. Conclusions: Prompt investigation of symptomatic, high‐risk women regardless of age may detect endometrial abnormalities at an early, potentially reversible stage. The prevention and management of identifiable high‐risk factors would help mitigate the risk of EC and associated diseases.

Vulvar intraepithelial neoplasia (VIN) is a precursor to vulvar squamous cell carcinoma and is defined histopathologically by the presence of atypia. VIN has been classified into two types: usual vulvar intraepithelial neoplasia (uVIN), which is also referred to as a vulvar high-grade squamous intra-epithelial lesion (HSIL), and differentiated VIN (dVIN). The former is associated with chronic infection by sub-types of the human papilloma virus (HPV), whereas dVIN is HPV-independent and frequently associated with lichen sclerosus. The distinction is important because dVIN has a greater risk of, and more rapid transit to, vulvar squamous cell carcinoma. Furthermore, dVIN-associated vulvar cancers have an increased risk of recurrence and higher mortality than those arising from HSIL. Molecular characterization of vulvar squamous cell carcinoma precursors using next-generation sequencing is a relatively novel, but rapidly advancing field. This review appraises recent studies that have investigated the risks of progression to vulvar malignancy associated with HSIL and dVIN, the prognosis of HPV-dependent and HPV-independent vulvar squamous cell carcinomas, and conducted next generation sequencing mutation analyses to elucidate the genomic profiles underlying VIN. These studies suggest that HSIL and dVIN are characterized by different underlying molecular alterations that may have important implications for treatment and follow-up of women diagnosed with vulvar squamous cell cancer.

In 2008, a quadrivalent human papillomavirus (HPV) vaccine (genotypes 6, 11, 16, 18) became available in New Zealand. This study investigated whether the proportion of cervical intraepithelial neoplasia grade 2 (CIN2) lesions associated with HPV genotypes 16 and 18 changed over time in young women recruited to a prospective CIN2 observational management trial (PRINCess) between 2013 and 2016. Partial HPV genotyping (16, 18, or other high risk HPV) was undertaken on n = 392 women under 25 years (mean age 21.8, range 17–24) with biopsy-diagnosed CIN2. High risk HPV genotypes were detected in 96% of women with CIN2 lesions. Between 2013 and 2016, the proportion of women whose liquid-based cytology samples were HPV 16 or 18 positive decreased from 43% to 13%. HPV vaccination status was known for 78% of women. Between 2013 and 2016, the proportion of HPV 16/18 positivity did not significantly change in HPV-vaccinated women, but decreased from 66% to 17% in unvaccinated women. The reducing proportion of HPV 16/18-related CIN2 in our cohort of young New Zealand women may be attributable to the introduction of a national HPV vaccination program. The substantial decrease in HPV 16/18 positivity observed in unvaccinated women is likely to be due to a herd effect., Highlights • 392 women under 25 years with CIN2 lesions were recruited between 2013 and 2016. • HPV16/18 positivity decreased from 43% of women in 2013–13% in 2016. • In vaccinated women, HPV16/18 positivity decreased from 17% in 2013 to 9% in 2016. • In unvaccinated women, HPV16/18 positivity decreased from 66% in 2013 to 17% in 2016. • Decreasing HPV16/18-related CIN2 may be due to HPV vaccination and herd effect.

Spindle cell or sarcomatoid squamous cell carcinoma is an uncommon variant of squamous cell carcinoma of the vulva (SCCV) with only 12 well-documented cases reported to date. Morphologically tumors may be biphasic or monophasic, and uncommonly include heterologous elements. Only 1 reported vulval tumor has previously been investigated for human papillomavirus DNA content. We describe 4 women with spindle cell (sarcomatoid) SCCV, 3 of which occurred de novo and 1 followed radiotherapy for previous SCCV. The tumors in all 4 women arose in a background of lichen sclerosus, and 3 were associated with vulval intraepithelial neoplasia differentiated (simplex) type. All tumors were negative for human papillomavirus DNA on polymerase chain reaction analysis. One case is the second reported with malignant heterologous elements described in the vulva. These tumors seem to be more aggressive than conventional SCCV.

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.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.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.

Squamous cell carcinoma of the vulva (SCCV) develops through either human papillomavirus (HPV)-dependent or HPV-independent pathways. Approximately 60% of SCCV arise independently of HPV, commonly in a background of an inflammatory dermatosis, particularly lichen sclerosus. The likely direct precursor to most of these lesions is vulvar intraepithelial neoplasia (VIN), differentiated type (dVIN), although the evidence is largely circumstantial. There are few reports of progression to carcinoma, and the natural history of this pathway is not well understood. Nevertheless, dVIN is widely regarded as a potentially aggressive lesion. We identified dVIN adjacent to SCCV in 97 of 212 women (45.8%). Twenty-four of the 97 women (24.7%) had biopsies performed at least 6 mo before presentation with SCCV; slides for 47 biopsies from 21 women were available for review. dVIN was identified in 18 biopsies from 8 women (38.1%), which in 14 biopsies had been previously unrecognized. The subsequent cancer developed in the same region as the previous biopsy showing dVIN in 6 of the 8 women. The median interval between biopsy and invasive cancer was 43.5 mo (range, 8-102 mo). dVIN-associated SCCV was strongly associated with both lichen sclerosus, and HPV-negative status compared with usual type VIN (relative risk=38.35 (9.755-150.8) and 0.06485 (0.02764-0.1522), respectively). This study adds to the evidence linking dVIN with SCCV, and indicates that both clinical and histologic underrecognition contribute to the apparent rarity of dVIN as a solitary diagnosis. The morphologic spectrum of dVIN is likely to be wider than commonly appreciated; however, histologically defining the lower threshold is difficult and controversial.

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.

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.

IntroductionAdenocarcinoma in situ (AIS) of the uterine cervix is the precursor to invasive endocervical adenocarcinoma. An excisional biopsy such as a cold knife cone biopsy (CKC) should be performed to exclude invasive adenocarcinoma. Loop electrosurgical excision procedure (LEEP) is an alternative modality to CKC but is controversial in AIS. There is a perception that there is a greater likelihood of incomplete excision of AIS with LEEP because the depth of excised tissue tends to be smaller and the tissue margins may show thermal artefact which can interfere with pathology assessment. In the USA, guidelines recommend that any treatment modality can be used to excise AIS, provided that the specimen remains intact with interpretable margins. However, there are no high-quality studies comparing LEEP with CKC and well-designed prospective studies are needed. If such a study were to show that LEEP was non-inferior to CKC for the outcomes of post-treatment persistence, recurrence and adenocarcinoma, LEEP could be recommended as an appropriate treatment option for AIS in selected patients. This would benefit women because, unlike CKC, LEEP does not require general anaesthesia and may be associated with reduced morbidity.Methods and analysisThe proposed exploratory study is a parallel group trial with an allocation ratio of 2:1 in favour of the intervention (LEEP: CKC). Participants are women aged ≥18 to ≤45 years diagnosed with AIS on cervical screening and/or colposcopically directed biopsy in Australia and New Zealand, who are to receive excisional treatment in a tertiary level centre.Ethics and disseminationEthical approval for the study has been granted by the St John of God Healthcare Human Research Ethics Committee (reference number #1137). Results from the study will be presented at conferences and published in a peer-reviewed scientific journal.RegistrationANZCTR registration number ACTRN12617000132347https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372173&isReview=true

Vulval squamous cell carcinoma is relatively rare; however, up to 20% of women have significant vulval symptoms during their lifetime. Formal screening programmes for vulval disease have not been established. The evidence for the use of vulval cytology and vulvoscopy is reviewed. No randomised-controlled trials have compared follow-up regimens, and although a few consensus documents have been published, formal guidelines are lacking in Grade A evidence. With increasing pressure on healthcare resources, the possibility of identifying high-risk groups to optimise the use of follow up in specialist clinics is explored. Vulval disease is uncommon and there is no evidence that screening would decrease incidence. If high-risk groups can be identified, follow up should take place in specialised vulval clinics with experienced clinicians who are trained in vulval disease. Women with uncomplicated vulval conditions should be discharged to patient-initiated follow up or primary care. Central to the reduction of mortality and morbidity is increased awareness of vulval conditions among women and improved education of healthcare professionals, with particular understanding of the importance of physical examination.