Prevaccine Human Papillomavirus Status in Invasive and Intraepithelial Lesions of the Vulva in New Zealand Women.

OBJECTIVE: The human papillomavirus (HPV) vaccine, introduced in New Zealand (NZ) in 2008, is predicted to substantially lower the incidence of HPV-associated precancers and cancers. The aim of this study is to estimate the proportion of vulvar intraepithelial neoplasia (VIN) lesions and invasive vulvar squamous cell carcinomas (SCCV) attributable to HPV in NZ women treated by the Auckland Regional Gynecological Oncology Service, covering an estimated 50% of the NZ population. MATERIALS AND METHODS: Polymerase chain reaction and reverse hybridization were used to analyze retrospective histologically proven SCCV from 1990 to 2007 and VIN lesions from 2000 to 2007 for HPV content and genotype in a collaborative study with the Catalan Institute of Oncology. Immunohistochemistry for p16INK4a was performed on SCCV, which were attributed to HPV if both tested positive. RESULTS: Polymerase chain reaction testing for HPV content and genotype was performed on 66 VIN lesions (all high-grade squamous intraepithelial lesions) and 189 SCCV. In addition, p16 immunohistochemistry was performed on 168 of the 189 SCCV (88.9%) tested for HPV-DNA. Overall, 61 SCCV cases (36.3%) were attributed to HPV (HPV+/p16+), and 89 SCCV cases (53%) were considered to have developed independently of HPV (HPV-/p16-). Known high-risk HPV genotypes were present in 96.8% of HPV-DNA-positive vulvar high-grade squamous intraepithelial lesions and 98.4% of HPV-attributable SCCV. Human papillomavirus 16 represented the most common genotype in both. CONCLUSIONS: Overall, the HPV vaccine is likely to substantially alter the profile of SCCV in our region. The results provide a baseline assessment of the HPV status of vulvar neoplasia before the introduction of the HPV vaccine.

Trends in HPV-dependent and HPV-independent vulvar cancers: The changing face of vulvar squamous cell carcinoma.

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 < .0001). 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.

Increasing incidence of endometrial carcinoma in a high-risk New Zealand community.

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 Maori, 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, Maori 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.

The Natural History of Vulvar Intraepithelial Neoplasia, Differentiated Type: Evidence for Progression and Diagnostic Challenges.

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.

Spindle cell carcinoma of the vulva: a series of 4 cases and review of the literature.

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.

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

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

Vaccines against cervical cancer.

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

Is modified vestibulectomy for localized provoked vulvodynia an effective long-term treatment? A follow-up study.

OBJECTIVE: To determine whether vestibulectomy is an effective long-term treatment and investigate the levels of patient satisfaction in women with localized provoked vulvodynia, and to provide long-term follow-up data from a cohort of women whose short-term success rates have been published previously. STUDY DESIGN: A retrospective case note review of 110 women with localized provoked vulvodynia and follow-up patient questionnaire. Patients were asked to quantify their pain scores before surgery, at 2 months after surgery and 1 year after surgery and score their satisfaction levels. RESULTS: Mean pain scores continued to improve throughout the first postoperative year. The mean score was 9.17 preoperatively, 5.24 at 2 months after surgery and 2.48 at 1 year after surgery. Eighty-three percent of patients would recommend the procedure as effective treatment of localized provoked vulvodynia. The overall mean satisfaction score was 7.96, and long-term success appears to be reflected by short-term results. CONCLUSION: Vestibulectomy is an effective long-term treatment for women with provoked localized vulvodynia; the procedure is associated with high levels of patient satisfaction and low complication rates. Shortterm success appears to be a good indicator of long-term improvement, and improve- ment continues throughout the first postoperative year.

Vulval squamous cell carcinoma occurring on a background of differentiated vulval intraepithelial neoplasia is more likely to recur: a review of 154 cases.

OBJECTIVE: To assess the frequency of recurrence of vulval carcinoma, arising from the background of usual-type vulval intraepithelial neoplasia (uVIN), differentiated VIN (dVIN, and nonneoplastic epithelial disorders (NNEDs). STUDY DESIGN: A retrospective review was conducted of 200 pathology specimens of vulval squamous cell carcinoma (VSCC) from 154 women over a 5-year period. The pathologic findings were reviewed where information of the adjacent pathology and number of recurrences of carcinoma for each woman were recorded. The number of recurrences was then correlated with the adjacent pathology using logistical regression analysis. RESULTS: The overall recurrence rate for vulval carcinoma was 22.6%. A single recurrence occurred in 12.9% of patients, whereas 5.8% had 2 recurrences and 3.9% has 3 recurrences of vulval carcinoma. The odds ratio (OR) of having a recurrence of VSCC associated with dVIN alone is 3.85 (95% CI 0.52, 28.24) and 4.3 when associated with dVIN in combination with NNEDs (95% CI 0.84, 21.92), whereas with VSCC associated with uVIN the OR is 1.35 (95% CI 0.20, 9.01). CONCLUSION: Vulval cancers arising on a background of dVIN appear more likely to recur than cancers arising from undifferentiated VIN; this is compounded by the concurrent presence of NNEDs.

Is localized, provoked vulvodynia an inflammatory condition?

OBJECTIVE: To perform a pilot study to investigate the relationship between localized, provoked vulvodynia of the vestibule and inflammatory cytokine expression. STUDY DESIGN: Women with a diagnosis of localized, provoked vulvodynia had tissue samples taken for vulvar expression of Interleukin 1alpha and 1beta and tumor necrosis factor alpha and compared to those of a control group. RESULTS: The study group did not show a significant increase in expression of inflammatory markers. CONCLUSION: There was no evidence in this study that localized, provoked vulvodynia is an inflammatory condition, as previously thought. This may be helpful in explaining why some women are resistant to medical or antiinflammatory treatment and may allow treatment to be prescribed more effectively.

Screening and follow up of vulval skin disorders.

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.

Estrogen receptor expression in vulvar vestibulitis syndrome.

OBJECTIVE: A pilot study was performed to investigate the relationship between vulvar vestibulitis syndrome and estrogen receptor expression. STUDY DESIGN: Women with a diagnosis of vulvar vestibulitis syndrome had tissue samples taken for vulvar estrogen receptor-alpha expression and this was compared with a control group. RESULTS: The study group showed a significant decrease in estrogen receptor expression, and 50% of the samples did not exhibit any receptor expression. CONCLUSION: There appears to be a subgroup of women with vulvar vestibulitis syndrome who exhibit abnormal estrogen receptor-alpha expression. This may be helpful in explaining why some women are resistant to medical treatment and may allow treatment to be prescribed more effectively.