Vulval Miscellania
Vulvar dermatosis
Best Pract Res Clin ObstetGynaecol. 2014 Oct;28(7):946-58. doi: 10.1016/j.bpobgyn.2014.07.005. Epub 2014 Jul 18.
Moyal-Barracco M1, Wendling J2.
Vulvar dermatoses are inflammatory conditions responsible for chronic or recurrent itching and soreness. The lesions are either circumscribed to the vulva or associated with extragenital localizations which may help to assess the diagnosis. They should be differentiated from infectious or neoplastic diseases which may have clinical similarities. As opposed to the majority of all dermatoses that have a benign and regular course, lichen sclerosus or lichen planus could exceptionally foster the occurrence of an epithelial cancer precursor which may evolve to squamous cell carcinoma. Topical corticosteroids are the mainstay treatment of vulvar dermatosis. We do not know if the treatment of vulvar lichen sclerosus and vulvar lichen planus prevents squamous cell carcinoma. matoses that have a benign and regular course, lichen sclerosus or lichen planus could exceptionally foster the occurrence of an epithelial cancer precursor which may evolve to squamous cell carcinoma. Topical corticosteroids are the mainstay treatment of vulvar dermatosis. We do not know if the treatment of vulvar lichen sclerosus and vulvar lichen planus prevents squamous cell carcinoma.
Pruritus in female patients
Biomed Res Int. 2014;2014:541867. doi: 10.1155/2014/541867. Epub 2014 Mar 10
Lambert J1.
Pruritus is a frequent symptom in many dermatological diseases. In this review we want to focus on not only itch problems specific to women, namely, pruritic vulvodermatoses, but also the specific pruritic dermatoses of pregnancy. The specific characteristics of the vulva and the hormonal changes during the different age periods make these dermatoses very particular. It seems that vulvar diseases are still underdiagnosed and undertreated. Pruritic vulvar diseases have a huge impact on quality of life. The most common pruritic diseases will be discussed, such as atopic and contact dermatitis, psoriasis, lichen sclerosis, lichen planus, and infectious vulvaginitis. We focus on the diagnostic issue of these diseases and will consider the general principles of therapy.
Non-infectious inflammatory genital lesions
Clin Dermatol. 2014 Mar-Apr;32(2):307-14. doi: 10.1016/j.clindermatol.2013.08.015.
Andreassi L1, Bilenchi R2.
The genitalia may be the site of non-infectious inflammatory lesions that are generally manifested as balanoposthitis and vulvovaginitis. In men, these forms constitute 50% of all balanoposthitis forms, and in women, vulvovaginitis frequency is even higher. They consist of genital locations of general skin diseases, such as psoriasis, lichen planus, lichen sclerosus, and other clinical entities with their own physiognomy, such as Zoon's balanitis-vulvitis. Diagnosis of genital non-infectious inflammatory lesions is usually made on clinical criteria. A biopsy is only necessary for the identification of clinical conditions that may simulate inflammatory form but are actually premalignant processes.
Vulvar skin disorders throughout lifetime: about some representative dermatoses
Biomed Res Int. 2014;2014:595286. doi: 10.1155/2014/595286. Epub 2014 Jan 8.
Doyen J1, Demoulin S2, Delbecque K3, Goffin F1, Kridelka F1, Delvenne P3.
The objective of this paper is to present general considerations which should be kept in mind by clinicians in charge of women with vulvar diseases. Four representative vulvar dermatoses are described. Lichen simplex chronicus is a pathological condition related to chemical and mechanical irritant agents. Detrimental effects of these irritants, in the presence of other dermatoses, have to be considered when therapeutic responses are unsatisfactory. Lichen sclerosus is the most common vulvar dermatosis in elderly. However, it should be kept in mind that it may be diagnosed at any age. Lichen planus, in spite of sharing a similar range of etiological factors with lichen sclerosus, is a very distinct entity. Finally, Paget's disease, although rare, is also described especially because of the challenge it represents both clinically and therapeutically.
High Prevalence of Sexual Dysfunction in a Vulvovaginal Specialty Clinic
J Low Genit Tract Dis. 2014 Sep 25. [Epub ahead of print]
Gordon D1, Gardella C, Eschenbach D, Mitchell CM.
OBJECTIVE: Our study evaluated the presence and predictors of sexual dysfunction in a vulvovaginal specialty clinic population.
MATERIALS AND METHODS: Women who presented to a vulvovaginal specialty clinic were eligible to enrol. The participants completed a questionnaire, including Female Sexual Function Index to assess sexual dysfunction and Patient Health Questionnaire (PHQ)-9 depression screen, and underwent a standardized physical examination, with vaginal swabs collected for wet mount and culture. Logistic regression assessed the relationship between sexual dysfunction and clinical diagnosis.
RESULTS: We enrolled 161 women, aged 18 to 80 years (median, 36 years), presenting with vulvovaginal complaints. Median symptom duration was 24 months; 131 women (81%) reported chronic symptoms (≥12 months). By PHQ-9, 28 women (17%) met depression criteria. In the month before assessment, 86 women (53%) experienced sexual dysfunction. Women had a primary diagnosis of vaginitis (n = 46 [29%]), vestibulodynia/vulvitis (n = 70 [43%]), lichen planus or lichen sclerosus (n = 24 [15%]). Controlling for age, we found that sexual dysfunction did not correlate with chronic symptoms (incidence rate ratio [IRR], 0.86; 95% confidence interval [CI], 0.50-1.48), depression (IRR, 1.24; 95% CI, 0.59-2.58), or presence of any of the 3 main diagnoses (IRR, 1.16; 95% CI, 0.47-2.88).
DISCUSSION: Sexual dysfunction is present in more than half of women presenting to a vulvovaginitis referral clinic, more than twice the rate in the wider population.
Crohn's disease of the vulva
J Crohns Colitis. 2014 Jul 1;8(7):563-70. doi: 10.1016/j.crohns.2013.10.009. Epub 2013 Nov 16.
Barret M1, de Parades V2, Battistella M3, Sokol H4, Lemarchand N5, Marteau P6.
Crohn's disease (CD) of the vulva is a rare, yet under recognized condition. Fistulae arising from the digestive tract account for the greater part of genital lesions in CD. However, cutaneous so-called metastatic lesions of the vulva have been reported in the literature. They are clinically challenging for gastroenterologists as well as for gynecologists, with numerous differential diagnoses, especially among venereal diseases, and require a multidisciplinary approach. The most frequently observed features of the disease are labial swelling, vulvar ulcers, and hypertrophic lesions. Biopsy samples for histological study are mandatory, in order to establish the diagnosis of vulvar CD. Treatment options include oral prolonged courses of metronidazole and systemic immunosuppressive therapy such as corticosteroids and azathioprine, with promising data published on the efficacy of infliximab. Surgery remains restricted to medical treatment failures or resection of unsightly lesions. Prospective studies or case series with long follow-up data are still missing to guide the treatment of this condition.
An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis
J Clin Pathol. 2014 Apr;67(4):290-4. doi: 10.1136/jclinpath-2013-202117. Epub 2014 Jan 7.
Reyes MC1, Cooper K.
There are two distinct types of vulvar intraepithelial neoplasia (VIN), which differ in their clinical presentation, aetiology, pathogenesis and histological/immunophenotypical features. One form driven by high-risk human papilloma virus infection usually occurs in young women and has been termed classic or usual VIN (uVIN). The other, not related to viral infection, occurs in postmenopausal women with chronic skin conditions such as lichen sclerosus and lichen simplex chronicus and is termed differentiated or simplex-type VIN. The latter is the precursor lesion of the most common type of squamous cell carcinoma (SCC) in the vulva, namely keratinizing SCC (representing 60% of cases). In contrast, uVIN usually gives rise to basaloid or warty SCC (40% of cases). The histological features of uVIN are similar to those of high grade lesions encountered in other lower anogenital tract sites (hyperchomatic nuclei with high nuclear to cytoplasmic ratios and increased mitotic activity). However, differentiated VIN has very subtle histopathological changes and often escapes diagnosis. Since uVIN is driven by high-risk human papilloma virus infections, p16 immunohistochemistry is diffusely positive in these lesions and is characterized with a high Ki-67 proliferation index. In contrast, differentiated or simplex-type VIN is consistently negative for p16 and the majority of the cases harbour TP53 mutations, correlating with p53 positivity by immunohistochemistry.
Activity, safety, and feasibility of cidofovir and imiquimod for treatment of vulval intraepithelial neoplasia (RT(3)VIN): a multicentre, open-label, randomised, phase 2 trial
Lancet Oncol. 2014 Nov;15(12):1361-8. doi: 10.1016/S1470-2045(14)70456-5. Epub 2014 Oct 7.
Tristram A1, Hurt CN2, Madden T3, Powell N1, Man S4, Hibbitts S1, Dutton P3, Jones S1, Nordin AJ5, Naik R6, Fiander A1, Griffiths G7.
BACKGROUND: Vulval intraepithelial neoplasia is a skin disorder affecting the vulva that, if left untreated, can become cancerous. Currently, the standard treatment for patients with vulval intraepithelial neoplasia is surgery, but this approach does not guarantee cure and can be disfiguring, causing physical and psychological problems, particularly in women of reproductive age. We aimed to assess the activity, safety, and feasibility of two topical treatments-cidofovir and imiquimod-as an alternative to surgery in female patients with vulval intraepithelial neoplasia.
METHODS: We recruited female patients (age 16 years or older) from 32 centres to an open-label, randomised, phase 2 trial. Eligibility criteria were biopsy-proven vulval intraepithelial neoplasia grade 3 and at least one lesion that could be measured accurately. We randomly allocated patients to topical treatment with either 1% cidofovir (supplied as a gel in a 10 g tube, to last 6 weeks) or 5% imiquimod (one 250 mg sachet for every application), to be self-applied three times a week for a maximum of 24 weeks. Randomisation (1:1) was done by stratified minimisation via a central computerised system, with stratification by hospital, disease focality, and presentation stage. The primary endpoint was a histologically confirmed complete response at the post-treatment assessment visit 6 weeks after the end of treatment (a maximum of 30 weeks after treatment started). Analysis of the primary endpoint was by intention to treat. Secondary outcomes were toxic effects (to assess safety) and adherence to treatment (to assess feasibility). We present results after all patients had reached the primary endpoint assessment point at 6 weeks; 2-year follow-up of complete responders continues. This trial is registered with Current Controlled Trials, ISRCTN 34420460.
FINDINGS: Between Oct 21, 2009, and Jan 11, 2013, 180 participants were enrolled to the study; 89 patients were randomly allocated cidofovir and 91 were assigned imiquimod. At the post-treatment assessment visit, a complete response had been achieved by 41 (46%; 90% CI 37·0-55·3) patients allocated cidofovir and by 42 (46%; 37·2-55·3) patients assigned imiquimod. After 6 weeks of treatment, 156 (87%) patients (78 in each group) had adhered to the treatment regimen. Five patients in the cidofovir group and seven in the imiquimod group either withdrew or were lost to follow-up before the first 6-week safety assessment. Adverse events of grade 3 or higher were reported in 31 (37%) of 84 patients allocated cidofovir and 39 (46%) of 84 patients assigned imiquimod; the most frequent grade 3 and 4 events were pain in the vulva, pruritus, fatigue, and headache.
INTERPRETATION: Cidofovir and imiquimod were active, safe, and feasible for treatment of vulval intraepithelial neoplasia and warrant further investigation in a phase 3 setting. Both drugs are effective alternatives to surgery for female patients with vulval intraepithelial neoplasia after exclusion of occult invasive disease.
Adjuvant topical treatment with imiquimod 5% after excisional surgery for VIN 2/3
Eur Rev Med Pharmacol Sci. 2014 Oct;18(19):2949-52.
Gentile M1, Bianchi P, Sesti F, Sopracordevole F, Biamonti A, Scirpa P, Schimberni M, Cozza G, Marziani R, Di Martino G, Catalano A, Milazzo GN, Zinna M, Caserta D, Frega A.
OBJECTIVE: Vulvar intraepithelial neoplasia (VIN) is a premalignant lesion of the vulva. The incidence of VIN is increasing. The surgery is currently the gold standard therapy for VIN, but Imiquimod could be a completion to surgery. The aim of this study is to compare the overall complete response, the recurrence rate and the risk factors for recurrence among two groups of patients: women with high grade VIN underwent surgery and patients treated with surgery plus Imiquimod.
PATIENTS AND METHODS: 80 patients with histologically diagnosed VIN 2/3 were enrolled in this prospective study. Our patients were divided into two groups: 40 women underwent surgery (A) and 40 patients were treated with surgery plus Imiquimod (B). All women had a 5-year follow-up. Recurrence rate and complete response were evaluated. The following patients' characteristics were analyzed: smoke, multifocal disease, multicentric disease, degree of the lesion.
RESULTS: In the group A recurrence rate was 44.8%, in the group B it was 48.4%. In both groups the presence of multifocal lesions (p = 0.02) and VIN 3 (p = 0.006) before treatment was associated with a higher risk of recurrence.
CONCLUSIONS: This study found that surgery remains the principal approach for VIN with regard to relapse and complete response since the treatment with Imiquimod associated with surgery didn't show a lower recurrence rate. Although the surgical treatments remain the best therapeutic option for VIN with regard to recurrence and overall complete response, the combined therapy seems to be an interesting modality, but further studies are needed.
Surgical interventions for high-grade vulval intraepithelial neoplasia
Cochrane Database Syst Rev. 2014 Mar 4;3:CD007928. doi: 10.1002/14651858.CD007928.pub3.
Kaushik S1, Pepas L, Nordin A, Bryant A, Dickinson HO.
BACKGROUND: This is an updated version of an original Cochrane review published in The Cochrane Library, 2011, Issue 1.Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its multicentric and multifocal nature. The incidence of this condition appears to be rising, particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for the surgical treatment of VIN has been to treat the symptoms and exclude any underlying malignancy, with the continued aim of preserving the vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity, thus impacting he individual's quality of life.
OBJECTIVES: To evaluate the effectiveness and safety of surgical interventions in women with high-grade VIN.
SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register and the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 11,2013 and
MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and contacted experts in the field.
SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared surgical interventions in adult women diagnosed with high-grade VIN.
DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias.
MAIN RESULTS: We identified one RCT, including 30 women, that met our inclusion criteria; this trial reported data on carbon dioxide (CO2) laser surgery versus cavitational ultrasonic surgical aspiration (CUSA). There were no statistically significant differences in the risks of disease recurrence after one year of follow-up, pain, scarring, dysuria or burning, adhesions, infection, abnormal discharge or eschar between women who underwent CO2 laser surgery and those who received CUSA. The trial lacked statistical power due to the small number of women in each group and the low number of observed events, but was at low risk of bias.
AUTHORS' CONCLUSIONS: The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. The absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of VIN therefore precludes any definitive guidance or recommendations for clinical practice.
Clinical responses to focused ultrasound applied to women with vulval intraepithelial neoplasia
J Ultrasound Med. 2014 Nov;33(11):1903-8. doi: 10.7863/ultra.33.11.1903.
Jia Y1, Wu J1, Xu M1, Tang L2, Li C1, Luo M1, Lou M1.
OBJECTIVES: Focused ultrasound waves penetrate superficial tissues and are aimed toward the target tissues at specific depths to exert their biological effects. Focused ultrasound has been applied for a number of clinical indications, including vulval dystrophies and low-grade vulval disease. This study aimed to assess the efficacy and safety of focused ultrasound treatment of high-grade vulval intraepithelial neoplasia (VIN).
METHODS: Eighteen women with high-grade VIN were recruited and treated with focused ultrasound. During each posttreatment follow-up, the safety of, side effects of, and clinical responses to focused ultrasound were evaluated by a standardized protocol, including symptoms, clinical appearance, and histologic findings.
RESULTS: All patients completed the designed follow-ups. In most cases, superficial mild to moderate swelling and blisters were seen in the focused ultrasound-treated skin but not in adjacent normal skin. Of the 18 patients, 16 showed complete histologic regression and resolution of symptoms 6 months after treatment. Of the other 2 patients, 1 showed complete regression after a second focused ultrasound treatment. The other patient did not respond to the focused ultrasound treatment and underwent a partial vulvectomy 6 months after treatment. None of the patients developed invasive carcinoma of the vulva during the follow-up period. One patient had local pruritus that was not alleviated by anti-inflammatory medication and local care.
CONCLUSIONS: The complete responses observed in women with high-grade VIN treated by focused ultrasound, together with the preservation of adjacent normal tissue, suggest that focused ultrasound may be considered for treatment of high-grade VIN.
Genetic and epigenetic changes in vulvar squamous cell carcinoma and its precursor lesions: A review of the current literature
Gynecol Oncol. 2014 Nov 14. pii: S0090-8258(14)01415-2. doi: 10.1016/j.ygyno.2014.11.002. [Epub ahead of print]
Trietsch MD1, Nooij LS2, Gaarenstroom KN3, van Poelgeest MI3.
Vulvar cancer is a relatively rare gynecologic malignancy with an annual incidence in developed countries of approximately 2 per 100,000 women. Vulvar squamous cell carcinoma (VSCC) has two etiological pathways: a high risk human papillomavirus (HPV)-dependent route, which has usual vulvar intraepithelial neoplasia (uVIN) as a precursor lesion, and an HPV-independent route, which is associated with differentiated VIN (dVIN), lichen sclerosus, and genetic alterations, such as TP53 mutations. Research on the molecular etiology of vulvar cancer has increased in the past years, not only regarding genetic alterations, but also epigenetic changes. In genetic alterations, a mutation irreversibly changes the nucleotide sequence of the DNA, or the number of copies of chromosomes per cell is altered. In epigenetics, the nucleotide sequence remains the same but genes can be 'switched' on or off by, for example, DNA methylation or histone modification. We searched the current literature on genetic and epigenetic alterations in VSCC and its precursor lesions. Many studies have reported a higher incidence of somatic mutations in HPV-negative tumors compared to HPV-positive tumors, with TP53 mutations being the most frequent. Allelic imbalances or loss of heterozygosity are more frequently found in higher stages of dysplasia and in invasive carcinomas, but it is not exclusive to HPV-negative tumors. A limited number of studies are available on epigenetic changes in vulvar lesions, with hypermethylation of CDKN2A being the most frequently investigated change. For most genes, hypermethylation occurs more frequently in vulvar squamous cell carcinomas than in precursor lesions. As most studies have focused on HPV infection and TP53 mutations, we suggest that more research should be performed using whole genome or next generation sequencing to determine the true landscape of genetic and epigenetic alterations in vulvar squamous cell carcinoma.