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1.
Int J Gynecol Cancer ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35914776

RESUMO

OBJECTIVES: We 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. METHODS: This 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. RESULTS: The 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)). CONCLUSIONS: HPV-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.

2.
J Low Genit Tract Dis ; 26(4): 323-327, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35930419

RESUMO

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.


Assuntos
Alphapapillomavirus , Carcinoma in Situ , Carcinoma de Células Escamosas , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Lesões Intraepiteliais Escamosas , Neoplasias Vulvares , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , DNA Viral/genética , Feminino , Humanos , Nova Zelândia/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Estudos Retrospectivos , Vulva/patologia , Neoplasias Vulvares/patologia
3.
Gynecol Oncol ; 157(2): 450-455, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32037194

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Infecções por Papillomavirus/epidemiologia , Neoplasias Vulvares/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nova Zelândia/epidemiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/patologia , Estudos Retrospectivos , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/patologia , Neoplasias Vulvares/virologia , Adulto Jovem
4.
Aust N Z J Obstet Gynaecol ; 60(2): 250-257, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31903554

RESUMO

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.


Assuntos
Neoplasias do Endométrio/epidemiologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
5.
Cancer Causes Control ; 30(2): 121-127, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30671687

RESUMO

PURPOSE: Endometrial cancer accounts for 3.9% of all female cancers globally, and its incidence appears to be increasing in women under 40 years of age. This paper investigated ethnic-specific trends in endometrial cancer across different age groups in New Zealand. METHODS: Women who were diagnosed with endometrial cancer between 1996 and 2012 were identified from the New Zealand Cancer Registry. Annual age-standardized incidence and mortality rates were calculated for each ethnicity (Maori, Pacific, and non-Maori non-Pacific) in four age groups (< 40, 40-49, 50-74, and 75 +). The estimates were adjusted for hysterectomy. Joinpoint regression analysis was used to assess trends over time and annual percentage changes (APCs) were estimated. RESULTS: Between 1996 and 2012, age-standardized incidence rates increased in all women and significantly in the < 40, 40-49, and 50-74 age groups (APC 9.22, 3.56, and 1.65 respectively). Incidence rates were highest in Pacific women and increased most rapidly in those under 50 years of age (APC 9.36). Conversely, age-standardized mortality rates decreased in all women and significantly in the 50-74 and 75 + age groups (APC - 5.25 and - 5.06 respectively), with the highest rate observed in Pacific women. CONCLUSION: Pacific women had the highest incidence of endometrial cancer and the trend was increasing, particularly in young women. This could be attributed, at least in part, to a high and increasing rate of obesity in these women and should be explored in future research.


Assuntos
Neoplasias do Endométrio/etnologia , Neoplasias do Endométrio/epidemiologia , Adulto , Idoso , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Nova Zelândia/etnologia , Obesidade , Grupos Populacionais , Sistema de Registros , Adulto Jovem
6.
Int J Gynecol Pathol ; 35(6): 574-584, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26974999

RESUMO

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.


Assuntos
Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Vulvares/patologia , Biomarcadores Tumorais/análise , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estudos Retrospectivos , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/biossíntese
7.
J Cutan Pathol ; 42(3): 222-226, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25407897

RESUMO

Angiomyofibroblastoma represents a rare, benign mesenchymal tumor with a predilection for the vulvovaginal region. Lipomatous change may occur but rarely comprises a substantial component of the lesion. There are only eight reports in the English language literature describing the lipomatous variant of this tumor. We describe a further lipomatous angiomyofibroblastoma that occurred on the labium majus of a 49-year-old woman. The histopathologic and immunohistochemical features are described, and the collective experience in the literature is reviewed.


Assuntos
Angiofibroma/patologia , Angiomioma/patologia , Neoplasias de Tecidos Moles/patologia , Angiofibroma/diagnóstico , Angiofibroma/cirurgia , Angiomioma/diagnóstico , Angiomioma/cirurgia , Glândulas Vestibulares Maiores/patologia , Diagnóstico Diferencial , Feminino , Humanos , Mesoderma/patologia , Mesoderma/cirurgia , Pessoa de Meia-Idade , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/cirurgia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgia , Neoplasias Vulvares/ultraestrutura
8.
Int J Gynecol Pathol ; 33(2): 203-12, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24487477

RESUMO

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.


Assuntos
Carcinoma in Situ/patologia , Carcinoma/patologia , Líquen Escleroso e Atrófico/patologia , Neoplasias Vulvares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos
9.
Int J Gynecol Pathol ; 30(5): 505-13, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21804399

RESUMO

Aggressive angiomyxoma (AA) is a benign, slow-growing tumor that characteristically occurs in women of reproductive age. Local recurrence is cited in 30% to 40% of cases. Wide local excision is the treatment of choice. However, recent reports suggest a role for hormone manipulation in the management of these tumors. The morphology and immunophenotype of AA overlap with that of other, mainly benign vulvovaginal mesenchymal tumors. Diagnosis rests primarily on hematoxylin and eosin staining features, and distinction is important in determining appropriate treatment and follow-up. Rearrangement of HMGA2 has been shown in AA, and reports suggest that HMGA2 immunohistochemistry may have a role in the routine diagnosis of AA, its distinction from mimics, and in the evaluation of margins. Furthermore, CDK4 immunopositivity has been described in AA. We describe a series of 9 cases of AA with typical histology and long-term follow-up, and evaluate the role of HMGA2, CDK4, estrogen, and progesterone immunohistochemistry. One of 9 women (11%) experienced recurrence, with the second at 17 years, which is the longest recorded in the English literature. HMGA2 immunohistochemistry was positive in 37.5% of cases, consistent with the reported frequency of HMGA2 gene rearrangement, and negative in all benign mimics. CDK4 immunoreactivity was weak, diagnostically not helpful, and of uncertain significance. Immunohistochemistry for estrogen and progesterone were positive in 87.5% of AAs, and were widely positive in control groups.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias dos Genitais Femininos/patologia , Mixoma/patologia , Adulto , Criança , Quinase 4 Dependente de Ciclina/análise , Quinase 4 Dependente de Ciclina/biossíntese , Feminino , Neoplasias dos Genitais Femininos/metabolismo , Proteína HMGA2/análise , Proteína HMGA2/biossíntese , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mixoma/metabolismo , Recidiva Local de Neoplasia/patologia , Receptores de Estrogênio/análise , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/análise , Receptores de Progesterona/biossíntese
10.
Eur J Cancer ; 49(16): 3450-61, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23886586

RESUMO

BACKGROUND: Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. METHODS: Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). RESULTS: Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). CONCLUSION: Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.


Assuntos
Carcinoma in Situ/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias Vulvares/virologia , Adulto , Algoritmos , Biomarcadores Tumorais/análise , Carcinoma in Situ/química , Carcinoma in Situ/patologia , Estudos Transversais , Inibidor p16 de Quinase Dependente de Ciclina/análise , Sondas de DNA de HPV , Feminino , Genótipo , Testes de DNA para Papilomavírus Humano , Humanos , Imuno-Histoquímica , Modelos Logísticos , Pessoa de Meia-Idade , Invasividade Neoplásica , Papillomaviridae/classificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos Retrospectivos , Regulação para Cima , Neoplasias Vulvares/química , Neoplasias Vulvares/patologia
11.
J Cutan Pathol ; 33(5): 383-8, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16640548

RESUMO

BACKGROUND: The most frequent molecular abnormality observed in dermatofibrosarcoma protuberans (DFSP) is the formation of a supernumerary ring chromosome or translocation resulting in fusion of the gene encoding the alpha-chain of type 1 collagen, COL1A1 from 17q22, to the platelet-derived growth factor beta-chain, PDGFB gene from 22q13. Rare cases documenting variant ring or marker chromosomes involving regions other than 17q22 and 22q13 have been reported. Further analysis in three of these cases demonstrated the presence of the COL1A1 and PDGFB genes. METHODS: We report a further case of DFSP with a rare variant ring chromosome. The tumor appeared to undergo accelerated growth during pregnancy, then metastasized following pregnancy. We describe the clinical, histological, immunohistochemical, and cytogenetic features. RESULTS: The metastatic tumor showed a variant r(17;?) chromosome. A locus-specific probe was required to demonstrate presence of the PDGFB gene within the ring, indicating cryptic molecular rearrangement between chromosomes 17 and 22, and recombination with an unknown chromosome. CONCLUSIONS: Cryptic rearrangement of chromosomes 17 and 22 should be suspected in variant ring chromosomes and translocations. Pregnancy may contribute to accelerated growth of DFSP, and delay in surgical resection should be avoided.


Assuntos
Dermatofibrossarcoma/genética , Dermatofibrossarcoma/patologia , Complicações Neoplásicas na Gravidez/genética , Cromossomos em Anel , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adulto , Antineoplásicos/uso terapêutico , Benzamidas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/secundário , Neoplasias da Mama/cirurgia , Dermatofibrossarcoma/secundário , Feminino , Humanos , Mesilato de Imatinib , Hibridização In Situ , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Mastectomia , Piperazinas/uso terapêutico , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Pirimidinas/uso terapêutico , Neoplasias Cutâneas/cirurgia
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