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Vulva Cancer

The vulva is the area of the external sex organs of a woman. It is made up of two outer lips (the labia majora), which are covered in pubic hair and surround two inner lips (the labia minora). Between these lips are the entrances to the vagina and the the urethra (the short tube that passes urine from the bladder). Cancer of the vulvar (known as vulval or valvar cancer) occurs where the cells of the vulva become abnormal and grow in an uncontrolled way. There are a number of different types of cancer of the vulva. Most (about 90%) are squamous cell carcinoma which develop in the flat squamous skin cells. Less common cancers of the vulva include vulval melanoma, adenocarcinoma, and verrucous carcinoma. Paget’s disease of the vulva is a pre-cancerous condition where glandular cells spread outwards and across the vulval skin.

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  • PubMed search for publications about Vulvar Cancer - Limit search to: [Reviews]

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    MeSH term: Vulvar Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Momeni M, Korotkaya Y, Carrasco G, Prasad-Hayes M
Adenoid Cystic Carcinoma of Bartholin's Gland: Case Report.
Acta Med Iran. 2016; 54(12):820-822 [PubMed] Related Publications
Primary adenoid cystic carcinoma (ACC) of Bartholin's gland is a rare gynecologic malignancy. We report a case of locally advanced ACC of Bartholin's gland. A 62-year-old presented with left Bartholin's gland carcinoma and underwent left radical vulvectomy, left-sided inguinal-femoral lymph node dissection, posterior pelvic exenteration, and pedicle abdominal muscle flap. On her 3 months follow-up exam she was disease free.Pelvic exenteration for thetreatment of this rare disease in the vulva is a potential curative option.

Joura EA, Pils S
Vaccines against human papillomavirus infections: protection against cancer, genital warts or both?
Clin Microbiol Infect. 2016; 22 Suppl 5:S125-S127 [PubMed] Related Publications
Since 2006, three vaccines against infections and disease caused by human papillomavirus (HPV) became available in Europe-in 2006 a quadrivalent HPV 6/11/16/18 vaccine, in 2007 a bivalent HPV 16/18 vaccine and in 2015 a nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine. HPV 16 and 18 are the most oncogenic HPV strains, causing about 70% of cervical and other HPV-related cancers, HPV 6 and 11 cause 85% of all genital warts. The additional types of the polyvalent vaccine account for about 20% of invasive cervical cancer and >35% of pre-cancer. The potential differences between these vaccines caused some debate. All three vaccines give a robust and long-lasting protection against the strains in the various vaccines. The promise of cross-protection against other types (i.e. HPV 31/33/45) and hence a broader cancer protection was not fulfilled because these observations were confounded by the vaccine efficacy against the vaccine types. Furthermore, cross-protection was not consistent over various studies, not durable and not consistently seen in the real world experience. The protection against disease caused by oncogenic HPV strains was not compromised by the protection against low-risk types causing genital warts. The most effective cancer protection to date can be expected by the nonavalent vaccine, data indicate a 97% efficacy against cervical and vulvovaginal pre-cancer caused by these nine HPV types.

Napoletano C, Bellati F, Ruscito I, et al.
Immunological and Clinical Impact of Cancer Stem Cells in Vulvar Cancer: Role of CD133/CD24/ABCG2-Expressing Cells.
Anticancer Res. 2016; 36(10):5109-5116 [PubMed] Related Publications
BACKGROUND: Cancer stem cells (CSCs) are tumour-initiating cells with self-renewal properties and chemo/radio-resistance. Regulatory T-cells (Tregs) influence CSCs through several mechanisms. In different solid tumours, the presence of both cell populations correlated with poor survival. In vulvar cancer, little is known regarding biological markers able to predict patient prognosis. We investigated the presence and clinical impact of CSCs and infiltrating Treg in primary vulvar cancer.
MATERIALS AND METHODS: Paraffin-embedded tissue specimens derived from 43 patients with vulvar cancer were analyzed by immunohistochemistry for the expression of prominin-1 (CD133), CD24, ATP-binding cassette sub-family G member 2 (ABCG2) (CSC markers) and forkhead box protein P3 (FOXP3) (Treg marker).
RESULTS: CD133 expression correlated with younger age at diagnosis (p<0.01), lymph-node metastasis (p<0.05) and larger tumour diameter (p<0.05). CD133(+) tumours showed a high FOXP3(+) T-cell infiltration. Overall survival and progression-free survival were not influenced by the expression of the analyzed biomarkers.
CONCLUSION: In vulvar cancer, CSCs were more frequently expressed in younger aged patients and those with aggressive disease. Their presence was also associated with high Treg infiltration, which contributes to the generation of an immunosuppressive milieu.

Lu YY, Lu CH, Wang HY
Clitoral Metastasis From Advanced Cervical Carcinoma on 18F-FDG-PET/CT.
Clin Nucl Med. 2017; 42(1):54-55 [PubMed] Related Publications
Metastatic tumors of the clitoris from cervical carcinoma are extremely rare. Here, we described a 54-year-old woman with clitoral metastasis from cervical carcinoma demonstrated on F-FDG PET/CT images.

Konstantinova AM, Shelekhova KV, Stewart CJ, et al.
Depth and Patterns of Adnexal Involvement in Primary Extramammary (Anogenital) Paget Disease: A Study of 178 Lesions From 146 Patients.
Am J Dermatopathol. 2016; 38(11):802-808 [PubMed] Related Publications
Extramammary Paget disease (EMPD) is a rare neoplasm usually presenting in the anogenital area, most commonly in the vulva. Adnexal involvement in primary EMPD is a very common feature and serves as a pathway for carcinoma to spread into deeper tissue. The depth of carcinomatous spread along the appendages and the patterns of adnexal involvement were studied in 178 lesions from 146 patients with primary EMPD. Hair follicles and eccrine ducts were the adnexa most commonly affected by carcinoma cells. The maximal depth of involvement was 3.6 mm in this series. When planning topical therapy or developing novel local treatment modalities for EMPD, this potential for significant deep spread along adnexa should be taken into account.

Amavi AK, Kouadio L, Adabra K, et al.
Surgical management for squamous cell carcinoma of vulva.
Pan Afr Med J. 2016; 24:145 [PubMed] Free Access to Full Article Related Publications
To analyze our surgical management and the result of squamous cell carcinoma (SCC) of vulva. Retrospectively, we collected 38 cases of SCC; 17 cases of them were early SCC and 21 cases were locally advanced. The patients underwent primary surgery. The survival was estimated using Kaplan-Meier analysis and the log rank test. The mean age was 60.78 years. Total vulvectomy was performed in all patients. Superficial and deep incision of bilateral inguinal lymphadenectomy was performed by separates incisions for SCC infiltrating more than 1mm. The average tumor size was 53 mm (10 to 140mm). Morbidity was 42.1%. Lateral resection margin ≥8mm was obtained in 57.1%. Eighteen patients benefited from adjuvant radiotherapy. The follow-up median was 19.4 months (6 to 61.5 month) with 05 recurrences in 12 months. The survival using the Kaplan-Meyer analysis at 5 years, was 62.1% (71.2%N(-) vs 46.7%N(+); p = 0.13). We identified two groups for locally advanced vulva cancer. Primary surgery keeps its place. Neo adjuvant radio chemotherapy followed by surgery is the alternative treatment for locally extensive lesions.

Nooij LS, Brand FA, Gaarenstroom KN, et al.
Risk factors and treatment for recurrent vulvar squamous cell carcinoma.
Crit Rev Oncol Hematol. 2016; 106:1-13 [PubMed] Related Publications
Recurrent disease occurs in 12-37% of patients with vulvar squamous cell carcinoma (VSCC). Decisions about treatment of recurrent VSCC mainly depend on the location of the recurrence and previous treatment, resulting in individualized and consensus-based approaches. Most recurrences (40-80%) occur within 2 years after initial treatment. Currently, wide local excision is the treatment of choice for local recurrences. Isolated local recurrence of VSCC has a good prognosis, with reported 5-year survival rates of up to 60%. Groin recurrences and distant recurrences are less common and have an extremely poor prognosis. For groin recurrences, surgery with or without (chemo) radiotherapy is a treatment option, depending on prior treatment. For distant recurrences, there are only palliative treatment options. In this review, we give an overview of the available literature and discuss epidemiology, risk factors, and prognostic factors for the different types of recurrent VSCC and we describe treatment options and clinical outcome.

Lawrie TA, Nordin A, Chakrabarti M
Medical and Surgical Treatments for Usual-Type Vulvar Intraepithelial Neoplasia.
JAMA Oncol. 2016; 2(12):1647-1648 [PubMed] Related Publications
Clinical Question: Which interventions are the most effective and tolerable for treating usual-type vulvar intraepithelial neoplasia?
Bottom Line: Provided cancer is not suspected, usual-type vulvar intraepithelial neoplasia treatment, including medical and surgical options, can be individualized to take into account the site, extent of disease, and a woman's preferences, with a commitment to long-term follow-up.

Siegler E, Segev Y, Mackuli L, et al.
Vulvar and Vaginal Cancer, Vulvar Intraepithelial Neoplasia 3 and Vaginal Intraepithelial Neoplasia 3: Experience of a Referral Institute.
Isr Med Assoc J. 2016; 18(5):286-9 [PubMed] Related Publications
BACKGROUND: Vulvar and vaginal malignant and premalignant lesions are uncommon and are clinically heterogeneous diseases with two pathways of carcinogenesis: human papillomavirus (HPV) induced or non-HPV induced.
OBJECTIVES: To evaluate the demographic and clinical characteristics associated with vulvar or vaginal cancer and vulvar and vaginal intraepithelial neoplasia 3 (VIN3, VAIN3).
METHODS: We conducted a retrospective chart review of 148 women with vulvar and vaginal malignancy and pre-malignancy for the period October 2004 to October 2012, and identified 59 and 19 patients with vulvar and vaginal cancer respectively, and 57 and 13 patients with VIN3 and VAIN3 respectively
RESULTS: The median age of vulvar cancer patients was 30 years older than that of VIN3 patients. HPV was found in 60% and 66.6% of vulvar and vaginal cancer patients respectively, and in 82.3% and 84.6% of patients with VIN3 and VAIN3 respectively. A history of cervical intraepithelial neoplasia (CIN) or warts was observed in 10% and 10.5% of vulvar and vaginal cancer patients respectively, and in 57.9% and 46% of patients with VIN3 and VAIN3 respectively. In 52.6% of patients the vaginal cancer was metastases from other organs.
CONCLUSIONS: Most women with vulvar carcinoma are older than 70 years. VIN3 and VAIN3 are associated with HPV infection and the most prevalent type is HPV16. Almost half the vaginal cancers are associated with metastases from other organs and almost half of VAIN3 is associated with past cervical dysplasia or carcinoma.

Ito R, Huang JJ, Wu JC, et al.
The versatility of profunda femoral artery perforator flap for oncological reconstruction after cancer resection-Clinical cases and review of literature.
J Surg Oncol. 2016; 114(2):193-201 [PubMed] Related Publications
BACKGROUND: The profunda feomris artery perforator (PAP) flap was recently revisited and gains popularity as an alternative method of autologous breast reconstruction. The purpose of this article is to demonstrate that PAP flap can be used reliably for reconstruction of various soft tissue defects.
METHODS: A total of 55 free PAP flaps and 16 pedicle PAP flaps were transferred in 63 patients. Each case was reviewed to verify a PAP flap was performed identifying defect location, flap size, flap design, and postoperative complications.
RESULTS: Seven flaps in five patients underwent breast reconstructions, 48 patients underwent head and neck reconstructions using free PAP flaps. The mean perforator number was 1.9, and the average pedicles length was 9.7 cm. The majority of perforators were musculocutaneous, and the others were septocutaneous. The mean ischemia time was 121.4 min. Minor complications included wound poor healing, flap partial necrosis, and pedicle vessels problems. Sixteen pedicle PAP flaps were transferred in 10 patients for vulvar reconstruction. Minor complications included urinary tract infection, poor wound healing, wound infection, hematoma.
CONCLUSIONS: The anatomy and number of perforators of PAP flap are reliable with adequate pedicle length. This flap can be an excellent option for reconstruction of most soft tissue defects. J. Surg. Oncol. 2016;114:193-201. © 2016 Wiley Periodicals, Inc.

Nooij LS, Dreef EJ, Smit VT, et al.
Stathmin is a highly sensitive and specific biomarker for vulvar high-grade squamous intraepithelial lesions.
J Clin Pathol. 2016; 69(12):1070-1075 [PubMed] Related Publications
AIMS: Differentiating between human papilloma virus-dependent vulvar low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) remains difficult in selected cases. Stathmin, a protein involved in cell cycle progression, might be a useful additional marker for this differentiation. The aim of this study was to investigate the additional diagnostic value of stathmin expression in vulvar intraepithelial neoplastic (VIN) lesions.
METHODS: Immunohistochemical analysis was used to evaluate stathmin, P16 and Ki67 expression in 91 samples, including LSILs (n=16), HSILs (n=50), differentiated VIN (dVIN; n=10), lichen sclerosis (LS; n=10) and normal vulvar tissue (n=5).
RESULTS: Stathmin was expressed in more than one-third of the epithelium in all HSILs and in 20% of LSILs. P16 and Ki67 were expressed in more than one-third of the epithelium in 94% of HSILs and in 13% and 40% of LSILs, respectively. Stathmin was expressed in more than one-third of the epithelium in 10% of the dVIN and in none of the LS or normal lesions. P16 and Ki67 expression was not present in more than one-third of the epithelium in any of these lesions. The sensitivity of stathmin for differentiating between LSILs and HSILs was 100% compared with a sensitivity of 94% for both p16 and Ki67. The specificity of stathmin, p16 and Ki67 was 80%, 87% and 60%, respectively.
CONCLUSIONS: Stathmin is a highly sensitive and specific biomarker for the diagnosis of vulvar HSIL. In addition to the more commonly used immunohistochemical markers p16 and Ki67, stathmin can be a useful diagnostic tool for identifying HSILs, especially in cases in which differentiating between LSIL and HSIL is difficult.

Patel D, Anderson TM, Lu Y
FDG-PET/CT of Vulvar Adenocarcinoma With Diffuse Metastases.
Clin Nucl Med. 2016; 41(9):710-1 [PubMed] Related Publications
A 52 year-old woman presented to her gynecologist with a 1-year history of a 1.5-cm left labial mass. Punch biopsy of the vulvar lesion revealed primary infiltrating adenocarcinoma. Staging FDG-PET/CT demonstrated multiorgan diffuse metastases.

Méry B, Ndong SM, Guy JB, et al.
Radiotherapy for gynecologic cancer in nonagenarian patients: a framework for new paradigms.
Chin J Cancer. 2016; 35:43 [PubMed] Free Access to Full Article Related Publications
No consensus exists regarding the role of radiotherapy in the management of gynecologic cancer in nonagenarian patients. We retrospectively reviewed the outcomes of 19 consecutive nonagenarian patients with gynecologic cancer (6 endometrial cancers, 6 cervical cancers, 4 vulvar cancers, and 3 vaginal cancers) who were treated with radiotherapy. Radiotherapy was performed mainly in a palliative setting (n = 12; 63.2%), with a median dose of 45 Gy (range, 6-76 Gy). Infrequent major acute or late toxicities were reported. Among 19 patients, 9 (47.4%) experienced tumor progression, 5 (26.3%) experienced complete response, 2 (10.5%) experienced stable disease and/or partial response. At last follow-up, 12 patients (63.2%) had died; most deaths (n = 9) occurred because of the cancer. These results suggest that radiotherapy is feasible in the treatment of nonagenarian patients with gynecologic cancer.

Mu Mu Shwe, Hlaing Myat Thu, Khin Saw Aye, et al.
Determination of Oncogenic Human Papillomavirus (HPV) Genotypes in Anogenital Cancers in Myanmar.
Acta Med Okayama. 2016; 70(2):103-10 [PubMed] Related Publications
Molecular and epidemiologic investigations suggest a causal role for human papillomavirus (HPV) in anogenital cancers. This study identified oncogenic HPV genotypes in anogenital cancers among men and women in a 2013 cross-sectional descriptive study in Myanmar. In total, 100 biopsy tissues of histologically confirmed anogenital cancers collected in 2008-2012 were studied, including 30 penile and 9 anal cancers from Yangon General Hospital and 61 vulvar cancers from Central Women's Hospital, Yangon. HPV-DNA testing and genotyping were performed by polymerase chain reaction-restriction fragment length polymorphism. Overall, 34% of anogenital cancers were HPV-positive. HPV was found in 44.4% of anal (4/9), 36.1% of vulvar (22/61), and 26.7% of penile (8/30) cancers. The most frequent genotypes in anal cancers were HPV 16 (75% ) and 18 (25% ). In vulvar cancers, HPV 33 was most common (40.9% ), followed by 16 (31.8% ), 31 (22.7% ), and 18 (4.6% ). In penile cancers, HPV 16 (62.5% ) was most common, followed by 33 (25% ) and 18 (12.5% ). This is the first report of evidencebased oncogenic HPV genotypes in anogenital cancers among men and women in Myanmar. This research provides valuable information for understanding the burden of HPV-associated cancers of the anus, penis, and vulva and considering the effectiveness of prophylactic HPV vaccination.

Alanyali S, Duran Ö, Özsaran Z, et al.
Treatment results and prognostic factors of patients with vulvar cancer treated with postoperative or definitive radiotherapy.
Tumori. 2016; 2016(3):311-5 [PubMed] Related Publications
PURPOSE: Vulvar cancer is a relatively uncommon type of gynecologic cancer. The aim of this study is to analyze the treatment results and prognostic factors of vulvar cancer.
METHODS: Forty-four vulvar cancer patients treated between 2000 and 2011 at the Department of Radiation Oncology, Ege University Faculty of Medicine, were retrospectively reviewed. External radiotherapy (RT) was applied with 6-18 MV linear accelerators with 1.8 Gy daily fractions with a median total dose of 50.4 Gy (45-59.4 Gy) for postoperative cases and 64.8 Gy (range 54-66 Gy) for definitive cases. Statistical analyses were performed with SPSS 13.0.
RESULTS: Among 44 patients with a median age of 68 years (range 28-86), 14 (31.8%) were treated with curative and 30 (68.2%) were treated with postoperative RT or radiochemotherapy (RCT). According to International Federation of Gynecology and Obstetrics staging, 11 (25%) had stage IB, 10 (22.7%) had stage II, 6 (13.6%) had stage IIIA, 5 (11.4%) had stage IIIB, and 12 (27.3%) had stage IVA disease. Within a median of 24 months (range 6-135) of follow-up, 11 (27.3%) patients had local recurrence, 8 had regional recurrence, 2 had both local and regional recurrence, and 6 had distant metastases. Five-year locoregional, disease-free, and overall survival rates were 45%, 40%, and 54%, respectively. Older age, poor tumor differentiation, positive surgical margin, and lymphovascular space invasion were found to be important prognostic factors for disease-related outcomes.
CONCLUSIONS: Prognosis of vulvar cancer remains poor even with a multidisciplinary approach. Molecular prognostic factors need to be defined for individualized treatment options to achieve better treatment results.

Chang TN, Lee CH, Lai CH, et al.
Profunda artery perforator flap for isolated vulvar defect reconstruction after oncological resection.
J Surg Oncol. 2016; 113(7):828-34 [PubMed] Related Publications
UNLABELLED: Isolated vulvar reconstruction using profunda artery-based perforator flaps have good functional as well as quality of life restoration. Surgical techniques, complications, and final evaluation using questionnaires are presented.
BACKGROUND: Vulvar reconstruction remains a great challenge to reconstructive surgeons. A local fasciocutaneous flap from the medial thigh is a good option with multiple choices of the donor arteries. Here, we extended the clinical application of a profunda perforator artery (PAP) flap with the design of an island pedicle flap.
METHODS: From 2012 to 2015, 12 female patients with vulvar cancer received tumor ablation and immediate reconstruction using a PAP flap. The flaps (n = 19) were divided into V-Y advancement perforator flap (group I, n = 4) and island pedicle perforator flap (group II, n = 15). All of the demographic data were collected and analyzed.
RESULTS: All of the flaps were transferred successfully, and all of the donor sites were closed without morbidities. Group II was superior to group I because of the smaller required flap size (P = 0.004), the smaller defect size/flap size ratio (P = 0.001), and a lower rate of post-op debridement (P = 0.037). The other parameters were not statistically significant.
CONCLUSIONS: PAP flap is a good choice for vulvar reconstruction. We preferred an island pedicle setting for its thin and pliable fasciocutaneous component and robust flap circulation. The favorable functional and aesthetic results can be achieved with limited donor site morbidities. J. Surg. Oncol. 2016;113:828-834. © 2016 Wiley Periodicals, Inc.

Narayama C, Ikeda M, Yasaka M, et al.
Aggressive Angiomyxoma of the Vulva with No Recurrence on a 5-year Follow up: A Case Report.
Tokai J Exp Clin Med. 2016; 41(1):42-5 [PubMed] Related Publications
We report a case of vulvar aggressive angiomyxoma (AA) which is a rare, slow growing and benign tumor of mesenchymal origin, but has a high risk of local recurrence. A 49-year-old Japanese female was referred to us with a large mass of the left vulva, measuring 15×9.5×9 centimeters. She underwent surgical excision of the tumor with no evidence of recurrence on a 5-year follow up. In this case, histopathological examination and immunohistochemical staining after excision revealed a diagnosis of vulvar AA with estrogen and progesterone receptors positive. Aggressive angiomyxoma of the vulva needs to be distinguished from benign myxoid tumor with a low risk of local recurrence as well as from malignant neoplasma. The first line treatment of AA is complete surgical excision with tumor free margins, it will reduce the recurrence.

Sofoudis C, Salakos N, Tolia M, et al.
Skin metastases of vulvar squamous cell carcinoma. Presentation of a rare case.
Eur J Gynaecol Oncol. 2016; 37(1):126-8 [PubMed] Related Publications
Skin metastases secondary to vulvar carcinoma is an infrequent clinical entity. The authors describe a case of squamous vulvar carcinoma, which presented with cutaneous involvement as a part of distant spread. After a radical vulvectomy, bilateral inguino-femoral lymphadenectomy, and adjuvant radiotherapy, the patient developed multiple cutaneous metastases in lower extremities. This case was unique in presentation, with skin metastases secondary from vulvar carcinoma, and indicated advance disease and poor prognosis.

Mousa A, Rahimi K, Warkus T
Neoadjuvant chemoradiotherapy followed by radical vulvectomy for adenoid cystic carcinoma of Bartholin's gland: a case report and review of the literature.
Eur J Gynaecol Oncol. 2016; 37(1):113-6 [PubMed] Related Publications
Adenoid cystic carcinoma (ACC) of Bartholin's gland is a rare variant and around 90 cases have been reported. Herein, the authors re port a locally advanced ACC of Bartholin's gland that was treated with neoadjuvant chemotherapy followed by right radical hemi-vulvectomy and reconstruction with a gracilis musculocutanous flap. There was no evidence of recurrence after three years of follow up.

Căpîlna ME, Szabo B, Nicolau CR, et al.
The mandatory role of groin lymphadenectomy in clinical Stages IB and II vulvar cancer.
Eur J Gynaecol Oncol. 2016; 37(1):86-8 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To analyze the prevalence of inguinofemoral lymph nodes metastases in clinical Stages IB-II vulva cancer.
MATERIALS AND METHODS: Twenty-two patients with FIGO Stages IB-II FIGO vulva cancer with no clinically and imagistic evidence of nodes metastases were treated in the present clinic. The surgical procedures consisted in radical vulvectomy plus inguinofemoral lym- phadenectomy.
RESULTS: The final pathological result was squamous carcinoma in 20 patients, vulva melanoma in one, and carcinosar- coma in one. The prevalence of positive lymph nodes was 45.4%. The median number of harvested lymph nodes was 14.0 per groin (between four and 27). Twelve patients (54.5%) developed some wound complications, but all were resolved. At the present time, 20 patients are alive, but the follow-up period is short for many of them; two patients died of disease.
CONCLUSION: The prevalence of groin metastases in Stages IB-II vulvar cancer is high. A thorough inguino-femoral dissection seems necessary, despite the high incidence of wound complications.

Koeck J, Lohr F, Buergy D, et al.
Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer.
Radiat Oncol. 2016; 11:53 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: While intensity modulated radiotherapy (IMRT) in anal cancer is feasible and improves high-dose conformality, the current RTOG/AGITG contouring atlas and planning guidelines lack specific instructions on how to proceed with external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends genital sparing on the basis of specific genital dose constraints. Recent pattern-of-relapse studies based on conventional techniques suggest that marginal miss might be a potential consequence of genital sparing. Our goal is to outline the potential scope and increase the awareness for this clinical issue.
METHODS: We present and discuss four patients with perigenital spread in anal cancer in both early and advanced stages (three at time of first diagnosis and one in form of relapse). Genital/perigenital spread was observed once as direct genital infiltration and thrice in form of perigenital lymphatic spread.
RESULTS: We review the available data regarding the potential consequences of genital sparing in anal cancer. Pattern-of-relapse studies in anal cancer after conventional radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest that genital sparing may occasionally result in marginal miss. An obvious hypothesis suggested by our report is that perigenital lymphovascular invasion might be associated with manifest inguinal N+ disease.
CONCLUSIONS: Local failure has low salvage rates in recent anal cancer treatment series. Perigenital spread may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are warranted. Until their publication, genital sparing should be applied with caution, PET/CT should be used when possible and meeting genital dose constraints should not be prioritized over CTV coverage, especially (but not only) in stage T3/4 and N+ disease.

Ngamkham J, Boonmark K, Phansri T
Detection and Type-Distribution of Human Papillomavirus in Vulva and Vaginal Abnormal Cytology Lesions and Cancer Tissues from Thai Women.
Asian Pac J Cancer Prev. 2016; 17(3):1129-34 [PubMed] Related Publications
Vulva and Vaginal cancers are rare among all gynecological cancers worldwide, including Thailand, and typically affect women in later life. Persistent high risk human papillomavirus (HR-HPV) infection is one of several important causes of cancer development. In this study, we focused on HPV investigation and specific type distribution from Thai women with abnormality lesions and cancers of the vulva and Vaginal. A total of ninety paraffin-embedded samples of vulva and Vaginal abnormalities and cancer cells with histologically confirmed were collected from Thai women, who were diagnosed in 2003-2012 at the National Cancer Institute, Thailand. HPV DNA was detected and genotyped using polymerase chain reaction and enzyme immunoassay with GP5+/ bio 6+ consensus specific primers and digoxigenin-labeled specific oligoprobes, respectively. The human β-globin gene was used as an internal control. Overall results represented that HPV frequency was 16/34 (47.1%) and 8/20 (40.0%) samples of vulva with cancer and abnormal cytology lesions, respectively, while, 3/5 (60%) and 16/33 (51.61%) samples of Vaginal cancer and abnormal cytology lesions, respectively, were HPV DNA positive. Single HPV type and multiple HPV type infection could be observed in both type of cancers and abnormal lesion samples in the different histological categorizes. HPV16 was the most frequent type in all cancers and abnormal cytology lesions, whereas HPV 18 was less frequent and could be detected as co-infection with other high risk HPV types. In addition, low risk types such as HPV 6, 11 and 70 could be detected in Vulva cancer and abnormal cytology lesion samples, whereas, all Vaginal cancer samples exhibited only high risk HPV types; HPV 16 and 31. In conclusion, from our results in this study we suggest that women with persistent high risk HPV type infection are at risk of developing vulva and Vaginal cancers and HPV 16 was observed at the highest frequent both of these, similar to the cervical cancer cases. Although the number of samples in this study was limited and might not represent the overall incidence and prevalence in Thai women, but the baseline data are of interest and suggest further study for primary cancer screening and/or developing the efficiency of prophylactic HPV vaccines in Thailand.

Cao H, Wang S, Zhang Z, Lou J
Prognostic Value of Overexpressed p16INK4a in Vulvar Cancer: A Meta-Analysis.
PLoS One. 2016; 11(3):e0152459 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: This study aimed to examine the prognostic value of overexpressed p16INK4a in vulvar cancer. Although the tumor suppressor p16INK4a has been shown to be of prognostic value in a wide variety of cancers and precancerous lesions, its role in the vulvar cancer is still unclear.
METHODS: All publications in English language on the association between p16INK4a and clinicopathological features of vulvar cancer were searched from Pubmed, Embase, and Web of Science, and those in Chinese language were identified manually and online from the China National Knowledge Infrastructure. Strict inclusion and exclusion criteria were followed. Odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were pooled to assess the strength of association. Publication bias was estimated using funnel plots and the Egger's regression test.
RESULTS: A total of 17 studies with 2309 patients were included. The p16INK4a overexpression was found to correlate significantly with the lower International Federation of Gynecology and Obstetrics stage (I+II vs III+IV; OR = 0.60, 95%CI: 0.41-0.86, P = 0.006), negative lymph node metastasis(negative vs positive; OR = 0.61, 95%CI: 0.39-0.95, P = 0.029), patient's age <55 (OR = 0.54, 95%CI: 0.31-0.96, P = 0.034), human papillomavirus-positive status (OR = 0.01, 95%CI: 0.00-0.11, P<0.001), and higher overall survival (RR = 0.53, 95%CI = 0.35-0.80, P = 0.003).
CONCLUSION: The p16INK4a might be associated with a higher survival and indicates better prognosis of vulvar cancer.

Germann D, Catarino R, Saiji E, et al.
Vulvar intraepithelial neoplasia grade 3 associated with Behçet's disease.
BMC Res Notes. 2016; 9:172 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Little information is available regarding the association between vulvar intraepithelial neoplasia grade 3 (VIN3) and Behçet's disease (BD). We report here concomitant VIN3 and genital ulcers in a patient with BD.
CASE: A 44-year-old Caucasian woman with a history of BD, which had been evolving for 6 years, presented with ulcerated and papillomatous lesions on the vulva. Biopsies revealed a multifocal VIN3 positive for high-risk human papillomavirus (HPV) 33. Multiple biopsies were performed to exclude invasive cancer and VIN3 was treated with laser vaporization.
CONCLUSION: We report clinical and anatomopathological features of a rare case of multifocal, high-risk, HPV-related VIN3. We also discuss the possible pathogenesis in the context of BD, featuring chronic ulceration and intrinsic or treatment-induced immunosuppression.

Rottmann M, Beck T, Burges A, et al.
Trends in surgery and outcomes of squamous cell vulvar cancer patients over a 16-year period (1998-2013): a population-based analysis.
J Cancer Res Clin Oncol. 2016; 142(6):1331-41 [PubMed] Related Publications
PURPOSE: The objective was to identify trends in surgery and the outcomes of squamous cell vulvar cancer in a population-based setting.
METHODS: A total of 1113 patients with squamous cell vulvar cancer diagnosed between 1998 and 2013 in the catchment area of the Munich Cancer Registry (population approximately 4.6 million) were analysed. Trends in prognostic factors and treatment were examined by comparing patients diagnosed between 1998 and 2008 with those diagnosed between 2009 and 2013. Cumulative incidence was used to calculate time to local (LR) and lymph node recurrence (LNR). Survival was analysed by the Kaplan-Meier method, calculation of relative survival (RS), and a Cox model.
RESULTS: The high median age at diagnosis of 75 years did not change significantly over time. In addition, no changes in the subsite of tumour or grading were noted. A decrease in patients undergoing complete vulvectomy from 27.7 to 17.8 % (p < 0.001) as well as an increase in the use of sentinel lymph node biopsy from 11.4 to 39.1 % (p < 0.001) was observed. However, time to LR (from 19 to 19 %) and time to LNR (from 9 to 9 %) as well as 5-year overall survival (from 55 to 55 %) and RS (from 66 to 63 %) were not significantly altered. After adjustment for prognostic factors, less radical locoregional surgery had no influence on survival.
CONCLUSION: Less radical locoregional surgery in vulvar cancer is increasingly implemented. Locoregional recurrence and survival have not been affected by these changes and are likely accompanied by an improvement in quality of life.

van der Linden M, Meeuwis KA, Bulten J, et al.
Paget disease of the vulva.
Crit Rev Oncol Hematol. 2016; 101:60-74 [PubMed] Related Publications
In this review, we provide an overview of the clinical aspects, histopathology, molecular genetics, and treatment options for Vulvar Paget's Disease (VPD), a rare skin disease, most commonly found in postmenopausal Caucasian women. The underlying cause of VPD remains not well understood. VPD is rarely associated with an underlying urogenital, gastrointestinal or vulvar carcinoma. In approximately 25% of the cases, VPD is invasive; in these cases, the prognosis is worse than in non-invasive cases. Recurrence rates in invasive VPD are high: 33% in cases with clear margins, and even higher when surgical margins are not clear, regardless of invasion. Historically, surgical excision has been the treatment of choice. Recent studies show that imiquimod cream may be an effective and safe alternative.

Clemente N, Alessandrini L, Rupolo M, et al.
Primary Non-Hodgkin's Lymphoma of the Vulva: A Case Report and Literature Review.
Medicine (Baltimore). 2016; 95(10):e3041 [PubMed] Free Access to Full Article Related Publications
The aim of this study was to add a new case of primary non-Hodgkin's malignant lymphoma of the vulva to the literature and to review the current literature.We searched the PubMed/MEDLINE databases for previous case reports using the key words "non-Hodgkin's malignant lymphoma of the vulva," "vulvar lymphoma," and "primary vulvar non-Hodgkin's lymphoma." We found 29 cases of primary vulvar non-Hodgkin's malignant lymphoma of the vulva reported until 2015. Among them, only 8 cases of diffuse large B-cell lymphoma (DLBCL), classified according to the most recent 2008 WHO classification, were reported.Moreover, only few studies reported the therapeutic management and clinical follow-up of patients affected by this condition.Due to its uncommon presentation, the primary non-Hodgkin's malignant lymphoma of the vulva can be undiagnosed; thus gynecologists, oncologists, and pathologists should be aware of this condition, as a correct diagnosis is essential for an appropriate therapeutic management.

Khosla D, Patel FD, Shukla AK, et al.
Dosimetric evaluation and clinical outcome in post-operative patients of carcinoma vulva treated with intensity-modulated radiotherapy.
Indian J Cancer. 2015 Oct-Dec; 52(4):670-5 [PubMed] Related Publications
BACKGROUND: To compare dosimetric parameters of intensity-modulated radiation therapy (IMRT) with 3D conformal radiotherapy (3DCRT) in post-operative patients of vulvar cancer and to assess clinical outcome and toxicity with IMRT.
MATERIALS AND METHODS: A total of 8 post-operative patients of vulvar cancer were treated with IMRT. All patients were also planned by 3DCRT for comparison with IMRT. The two plans were compared in terms of conformity index, homogeneity index, tumor control probability (TCP) and normal tissue complication probability (NTCP) for the planning target volume and organs at risk (OAR).
RESULTS: IMRT resulted in significantly lesser doses to rectum, bladder, bowel and femoral head as compared with 3DCRT plans. Mean conformity and homogeneity indices were better and within range with IMRT. The TCP was comparable between the two treatment plans and NTCP for rectum, bladder, bowel and femoral head was significantly less with IMRT as compared with 3DCRT. Treatment was well-tolerated and none of the patients developed Grade 3 or higher toxicity.
CONCLUSION: IMRT yielded superior plans with respect to target coverage, homogeneity and conformality while lowering dose to adjacent OAR as compared with 3DCRT. Thus, IMRT offers a reduction in NTCP while maintaining TCP.

Kaku Y, Goto K, Kabashima K
Myoepithelioma-like Tumor of the Vulvar Region Presenting as a Nonmyxoid Spindle-Cell Neoplasm: A Potential Histologic Mimicker of Solitary Fibrous Tumor.
Am J Dermatopathol. 2016; 38(7):e87-9 [PubMed] Related Publications
A new entity termed "myoepithelioma-like tumor of the vulvar region (MELTVR)" has been proposed as a rare mesenchymal neoplasm of the vulvar area. Histologically, MELTVRs are usually similar to soft tissue myoepitheliomas; however, they have a characteristic immunoprofile, including positivity for estrogen receptor and negativity for S100 protein, and loss of SMARCB1 expression. In this first known case report of MELTVR, the authors present a case of MELTVR that was histologically categorized in a nonmyxoid spindle-cell tumor group and resembled solitary fibrous tumor rather than soft tissue myoepithelioma.

Bradbury M, Cabrera S, García-Jiménez A, et al.
Vulvar intraepithelial neoplasia: clinical presentation, management and outcomes in women infected with HIV.
AIDS. 2016; 30(6):859-68 [PubMed] Related Publications
OBJECTIVE: Immunocompromised patients are at increased risk of developing preinvasive lesions of the lower genital tract. There are a limited number of studies on vulvar intraepithelial neoplasia (VIN) in HIV-positive women. We aimed to review the clinical presentation of VIN, management and survival outcomes in this group of patients.
DESIGN: Observational cohort study.
METHODS: Data was collected from women diagnosed with VIN at the Hospital Vall d'Hebron between September 1994 and October 2011. The main outcome measures were recurrence-free survival (RFS) and progression-free survival (PFS). Risk factors for recurrence and progression were assessed using univariate and multivariate analyses.
RESULTS: Thirty-seven out of 107 women were HIV positive (34.6%). The median follow-up time was 32 (range 12-179) months. Compared with the HIV-negative group, HIV-positive women were younger (median age 37 vs. 44 years, P = 0.003) and presented with multifocal and multicentric disease more frequently (63.6 vs. 22.2% and 84.8 vs. 43.3%, respectively, P < 0.0001). RFS and PFS were lower in the HIV-positive group (42.4 vs. 71.4% P = 0.043 and 69.7 vs. 95.2% P = 0.006, respectively). RFS was significantly associated to multicentric and multifocal disease on multivariate analysis. PFS was associated to HIV infection on univariate analysis.
CONCLUSION: HIV-positive women are at increased risk of developing VIN and frequently present at a younger age with multifocal and multicentric disease. They have shorter RFS and PFS compared with HIV-negative women. Close surveillance of the lower genital tract is mandatory to enable early recognition and treatment of any suspicious lesions. Close follow-up after treatment of VIN is essential to exclude early recurrence or progression.

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