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Cancers Jan 2022The aim of this review was an update of vulvar cancer incidence rates and trends and of all known and putative risk factors for the disease. The most recent incidence... (Review)
Review
The aim of this review was an update of vulvar cancer incidence rates and trends and of all known and putative risk factors for the disease. The most recent incidence data were sought from official sources (WHO ). To obtain an estimate of time trends in some areas, we compared data from with the few available studies that measured incidence using comparable methods. With respect to risk factors, a systematic PubMed search identified 1585 relevant articles published between 1980 and 2021. Abstracts and full texts were screened. Sixty-nine eligible original cohort and case-control studies were selected. Information was extracted using a PRISMA predesigned form. Nineteen risk factors, or risk factor categories, were investigated by two or more original studies. Solitary, unreplicated studies addressed the putative role of eight more factors. Recent advances have provided further evidence supporting the carcinogenic model centred on human papillomavirus infection with different defects of the immune function. Conversely, the model centred on the role of vulvar lichen sclerosus and the often associated differentiated vulvar intraepithelial neoplasia has continued to be epidemiologically understudied. More research on the association between these two conditions and vulvar cancer is a priority.
PubMed: 35053552
DOI: 10.3390/cancers14020389 -
Medical and surgical interventions for the treatment of usual-type vulval intraepithelial neoplasia.The Cochrane Database of Systematic... Jan 2016Usual-type vulval intraepithelial neoplasia (uVIN) is a pre-cancerous condition of the vulval skin. Also known as high-grade VIN, VIN 2/3 or high-grade vulval squamous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Usual-type vulval intraepithelial neoplasia (uVIN) is a pre-cancerous condition of the vulval skin. Also known as high-grade VIN, VIN 2/3 or high-grade vulval squamous intraepithelial lesion (HSIL), uVIN is associated with high-risk subtype human papilloma virus (HPV) infection. The condition causes distressing vulval symptoms in the majority of affected women and may progress to vulval cancer, therefore is usually actively managed. There is no consensus on the optimal management of uVIN. High morbidity and recurrence rates associated with surgical treatments make less invasive treatments highly desirable.
OBJECTIVES
To determine which interventions are the most effective, safe and tolerable for treating women with uVIN.
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Issue 8 2015, MEDLINE and EMBASE (up to 1 September 2015). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that assessed medical and surgical interventions in women with uVIN. If no RCTs were available, we included non-randomised studies (NRSs) with concurrent comparison groups that controlled for baseline case mix in multivariate analysis.
DATA COLLECTION AND ANALYSIS
We used Cochrane methodology with two review authors independently extracting data and assessing risk of bias. Where possible, we synthesised data in meta-analyses using random-effects methods. Network meta-analysis was not possible due to insufficient data.
MAIN RESULTS
We included six RCTs involving 327 women and five NRSs involving 648 women. The condition was variously named by investigators as uVIN, VIN2/3 or high-grade VIN. Five RCTs evaluated medical treatments (imiquimod, cidofovir, indole-3 carbinol), and six studies (one RCT and five NRSs) evaluated surgical treatments or photodynamic therapy. We judged two RCTs and four NRSs to be at a high or unclear risk of bias; we considered the others at relatively low risk of bias. Types of outcome measures reported in NRSs varied and we were unable to pool NRS data. Medical interventions: Topical imiquimod was more effective than placebo in achieving a response (complete or partial) to treatment at five to six months post-randomisation (three RCTs, 104 women; risk ratio (RR) 11.95, 95% confidence interval (CI) 3.21 to 44.51; high-quality evidence). At five to six months, a complete response occurred in 36/62 (58%) and 0/42 (0%) women in the imiquimod and placebo groups, respectively (RR 14.40, 95% CI 2.97 to 69.80). Moderate-quality evidence suggested that the complete response was sustained at one year (one RCT, nine complete responses out of 52 women (38%)) and beyond, particularly in women with smaller VIN lesions. Histologically confirmed complete response rates with imiquimod versus cidofovir at six months were 45% (41/91) and 46% (41/89), respectively (one RCT, 180 women; RR 1.00, 95% CI 0.73 to 1.37; moderate-quality evidence). Twelve-month data from this trial are awaited; however, interim findings suggested that complete responses were sustained at 12 months. Only one trial reported vulval cancer at one year (1/24 and 2/23 in imiquimod and placebo groups, respectively). Adverse events were more common with imiquimod than placebo and dose reductions occurred more frequently in the imiquimod group than in the placebo group (two RCTs, 83 women; RR 7.77, 95% CI 1.61 to 37.36; high-quality evidence). Headache, fatigue and discontinuation were slightly more common with imiquimod than cidofovir (moderate-quality evidence). Quality of life scores reported in one trial (52 women) were not significantly different for imiquimod and placebo. The evidence of effectiveness of topical treatments in immunosuppressed women was scant. There was insufficient evidence on other medical interventions. Surgical and other interventions: Low-quality evidence from the best included NRS indicated, when data were adjusted for confounders, that there was little difference in the risk of VIN recurrence between surgical excision and laser vaporisation. Recurrence occurred in 51% (37/70) of women overall, at a median of 14 months, and was more common in multifocal than unifocal lesions (66% versus 34%). Vulval cancer occurred in 11 women (15.1%) overall at a median of 71.5 months (9 to 259 months). The risk of vulval cancer did not differ significantly between excision and laser vaporisation in any of the NRSs; however, events were too few for robust findings. Alternative surgical procedures that might be as effective include Cavitron ultrasonic surgical aspiration (CUSA) and loop electrosurgical excision (LEEP) procedures, based on low- to very low-quality evidence, respectively. Very low-quality evidence also suggested that photodynamic therapy may be a useful treatment option.We found one ongoing RCT of medical treatment (imiquimod) compared with surgical treatment.
AUTHORS' CONCLUSIONS
Topical treatment (imiquimod or cidofovir) may effectively treat about half of uVIN cases after a 16-week course of treatment, but the evidence on whether this effect is sustained is limited. Factors predicting response to treatment are not clear, but small lesions may be more likely to respond. The relative risk of progression to vulval cancer is uncertain. However, imiquimod and cidofovir appear to be relatively well tolerated and may be favoured by some women over primary surgical treatment.There is currently no evidence on how medical treatment compares with surgical treatment. Women who undergo surgical treatment for uVIN have about a 50% chance of the condition recurring one year later, irrespective of whether treatment is by surgical excision or laser vaporisation. Multifocal uVIN lesions are at a higher risk of recurrence and progression, and pose greater therapeutic dilemmas than unifocal lesions. If occult cancer is suspected despite a biopsy diagnosis of uVIN, surgical excision remains the treatment of choice. If occult cancer is not a concern, treatment needs to be individualised to take into account the site and extent of disease, and a woman's preferences. Combined modalities may hold the key to optimal treatment of this complex disease.
Topics: Adult; Aminoquinolines; Antineoplastic Agents; Carcinoma in Situ; Cidofovir; Cytosine; Disease Progression; Female; Humans; Imiquimod; Indoles; Laser Therapy; Neoplasm Recurrence, Local; Organophosphonates; Photochemotherapy; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome; Vulvar Neoplasms
PubMed: 26728940
DOI: 10.1002/14651858.CD011837.pub2 -
PloS One 2015To systematically review previous studies and to evaluate the feasibility and safety of video endoscopic inguinal lymphadenectomy (VEIL) in vulvar cancer. (Review)
Review
OBJECTIVE
To systematically review previous studies and to evaluate the feasibility and safety of video endoscopic inguinal lymphadenectomy (VEIL) in vulvar cancer.
METHODS
We conducted a comprehensive review of studies published through September 2014 to retrieve all relevant articles. The PubMed, EMBASE, Web of Science, Cochrane Library, Wan Fang Data and Chinese National Knowledge Infrastructure databases were systematically searched for all relevant studies published in English or Chinese through September 2014. Data were abstracted independently by two reviewers, and any differences were resolved by consensus.
RESULTS
A total of 9 studies containing 249 VEIL procedures involving 138 patients were reviewed. Of the 249 VEIL procedures, only 1 (0.4%) was converted to an open procedure for suturing because of injury to the femoral vein. The range of operative time was 62 to 110 minutes, and the range of estimated blood loss was 5.5 to 22 ml. The range of the number of harvested lymph nodes was 7.3 to 16. The length of hospital stay varied from 7 to 13.6 days across reports. The incidence of lymph node metastasis was 19.7% (27/138), and the recurrence rate was 4.3% (3/70) within 3 to 41 months of follow-up. One or more short-term complications were documented in 18 of 138 (13.0%) patients. Complications after VEIL were observed in 14 (10.13%) patients and in 15 (6.0%) of the VEIL cases, including major lymphocyst formation in 9 (3.6%), lymphorrhea in 2 (0.8%), inguinal wound infection without wound breakdown in 3 (1.2%) and lymphedema in 1 (0.4%).
CONCLUSIONS
VEIL appears to be a feasible procedure in the management of vulvar cancer. There may be potential benefits that result in lower morbidity compared to traditional methods, but this has yet to be objectively proven.
Topics: Bacterial Infections; Blood Loss, Surgical; Female; Humans; Length of Stay; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Lymphocele; Operative Time; Postoperative Complications; Treatment Outcome; Video-Assisted Surgery; Vulva; Vulvar Neoplasms
PubMed: 26496391
DOI: 10.1371/journal.pone.0140873 -
Cancers Feb 2021According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17-41... (Review)
Review
According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17-41 years). The tumor size range was 0.3-15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5-48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.
PubMed: 33671249
DOI: 10.3390/cancers13040836 -
Journal of Clinical Medicine Jun 2023The most important causative agent of neoplasms in the anogenital area is the human papillomavirus (HPV). Due to the anatomical proximity of the genital and anus area... (Review)
Review
BACKGROUND
The most important causative agent of neoplasms in the anogenital area is the human papillomavirus (HPV). Due to the anatomical proximity of the genital and anus area and the ease with which HPV infection is transmitted, it seems that patients after the treatment of HPV-related gynecological diseases may have an increased risk of developing a second HPV-related neoplasm anal cancer. The aim of this study was to determine the risk of anal intraepithelial neoplasia (AIN) and anal cancer (AC) among patients after the treatment of HPV-related gynecological diseases.
METHODS
We conducted a comprehensive review of the available literature from multiple databases. The study was performed following and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. Moreover, we assessed the quality of each study using QUADAS-2.
RESULTS
Twenty-five studies were included in the final analysis. Patients after the treatment of HPV-related gynecological diseases have a significantly higher risk of AC (mean standardized incidence ratio (SIR) = 5.387, mean incidence risk (IR) = 0.096%, mean IR per 100,000 person-years = 10.37) and AIN (mean IR = 23.683%) compared to the population risk.
CONCLUSIONS
patients with HPV-related gynecological diseases should constitute a group for which an appropriate primary and secondary screening for AC should be introduced.
PubMed: 37445251
DOI: 10.3390/jcm12134216 -
Precursor lesions of vulvar squamous cell carcinoma - histology and biomarkers: A systematic review.Critical Reviews in Oncology/hematology Mar 2020The precursor lesion of vulvar squamous cell carcinoma (VSCC), namely vulvar intraepithelial neoplasia (VIN), is classified as: human papillomavirus (HPV)-related high...
The precursor lesion of vulvar squamous cell carcinoma (VSCC), namely vulvar intraepithelial neoplasia (VIN), is classified as: human papillomavirus (HPV)-related high grade squamous intraepithelial lesion (HSIL), and HPV-independent differentiated VIN (dVIN). Traditionally, histology and immunohistochemistry (IHC) have been the basis of diagnosis and classification of VIN. HSIL shows conspicuous histological atypia, and positivity on p16-IHC, whereas dVIN shows less obvious histological atypia, and overexpression or null-pattern on p53-IHC. For both types of VIN, other diagnostic immunohistochemical markers have also been evaluated. Molecular characterization of VIN has been attempted in few recent studies, and novel genotypic subtypes of HPV-independent VSCC and VIN have been identified. This systematic review appraises the VSCC precursors identified so far, focusing on histology and biomarkers (immunohistochemical and molecular). To gain further insights into the carcinogenesis and to identify additional potential biomarkers, gene expression omnibus (GEO) datasets on VSCC were analyzed; the results are presented.
Topics: Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Humans; Papillomaviridae; Papillomavirus Infections; Vulvar Neoplasms; Uterine Cervical Dysplasia
PubMed: 32058913
DOI: 10.1016/j.critrevonc.2020.102866 -
BMC Cancer Jun 2019Human papilloma virus (HPV) associated cervical cancer remains a global concern particular, in Sub-Saharan Africa (SSA) where the impact is felt most. Evidence show that...
BACKGROUND
Human papilloma virus (HPV) associated cervical cancer remains a global concern particular, in Sub-Saharan Africa (SSA) where the impact is felt most. Evidence show that many other cancers such as vaginal, anal, oropharyngeal, penile are because of persistent infection with HPV especially, high-risk types.
AIM
We mapped evidence on the incidence, prevalence, mortality, and the trends of human papillomavirus-related cancers in SSA.
METHODS
A comprehensive literature search was conducted from several databases including PubMed, Google scholar, Science Direct, and CINAHL and MEDLINE via EBSCOhost as well as World Health Organization website for grey literature. Studies reporting HPV-related cancers in SSA outcomes including prevalence, incidence, mortality, and trends were included in this study. The risk of bias of the included studies were assessed using the mixed methods appraisal tool version 2011. We employed PRISMA (preferred reporting items for systematic reviews and meta-analyses) to report the search results. Thematic analysis used to reveal the emerging themes from the included studies.
RESULTS
Seventy-four (74) studies were retrieved at full article screening, eight of them (six reviews, and two quantitative study) were eligible for data extraction. The degree of agreement between the two independent reviewers following full article screening, was 86.49% agreement versus 64.57% likely by chance which constituted moderate to significant agreement (Kappa statistic = 0.62, p-value< 0.05). Of the eight included studies, four (50%) studies generalized about SSA with no country of interest; two (25%) studies were conducted in Nigeria; one (12.5%) reported about Uganda, Zambia, Guinea, Malawi Tanzania, Mali, Mozambique, Zimbabwe; and one (12.5%) reported about Ethiopia, Senegal, Zimbabwe and Uganda. These eight included studies reported evidence on more than one outcome of interest. Four studies reported about the prevalence of HPV-related cancers, seven studies reported about the incidence, four studies reported about mortality, and four studies reported about the trends of HPV-related cancers.
CONCLUSION
This study observation highlighted a gap of knowledge regarding the epidemiological data on the recent HPV prevalence in SSA, which will have a potential impact in determining the distribution of HPV on different body sites (cervix, penis, vagina, vulva, anus and oropharynx). Ongoing research projects are recommended in SSA to enhance the value of HPV, and HPV-associated cancers epidemiological data to inform strategies or/and policies on prevention, diagnosis, and treatment of HPV-related conditions.
Topics: Africa South of the Sahara; Anus Neoplasms; Female; Humans; Incidence; Male; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Penile Neoplasms; Prevalence; Uterine Cervical Neoplasms; Vaginal Neoplasms
PubMed: 31185951
DOI: 10.1186/s12885-019-5781-3