-
BMJ (Clinical Research Ed.) Aug 2022To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the efficacy of human papillomavirus (HPV) vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment.
DESIGN
Systematic review and meta-analysis DATA SOURCES: PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov were screened from inception to 31 March 2021.
REVIEW METHODS
Studies reporting on the risk of HPV infection and recurrence of disease related to HPV infection after local surgical treatment of preinvasive genital disease in individuals who were vaccinated were included. The primary outcome measure was risk of recurrence of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) after local surgical treatment, with follow-up as reported by individual studies. Secondary outcome measures were risk of HPV infection or other lesions related to HPV infection. Independent and in duplicate data extraction and quality assessment were performed with ROBINS-I and RoB-2 tools for observational studies and randomised controlled trials, respectively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was implemented for the primary outcome. Observational studies and randomised controlled trials were analysed separately from post hoc analyses of randomised controlled trials. Pooled risk ratios and 95% confidence intervals were calculated with a random effects meta-analysis model. The restricted maximum likelihood was used as an estimator for heterogeneity, and the Hartung-Knapp-Sidik-Jonkman method was used to derive confidence intervals.
RESULTS
22 articles met the inclusion criteria of the review; 18 of these studies also reported data from a non-vaccinated group and were included in the meta-analyses (12 observational studies, two randomised controlled trials, and four post hoc analyses of randomised controlled trials). The risk of recurrence of CIN2+ was reduced in individuals who were vaccinated compared with those who were not vaccinated (11 studies, 19 909 participants; risk ratio 0.43, 95% confidence interval 0.30 to 0.60; I=58%, τ=0.14, median follow-up 36 months, interquartile range 24-43.5). The effect estimate was even stronger when the risk of recurrence of CIN2+ was assessed for disease related to HPV subtypes HPV16 or HPV18 (six studies, 1879 participants; risk ratio 0.26, 95% confidence interval 0.16 to 0.43; I=0%, τ=0). Confidence in the meta-analysis for CIN2+ overall and CIN2+ related to HPV16 or HPV18, assessed by GRADE, ranged from very low to moderate, probably because of publication bias and inconsistency in the studies included in the meta-analysis. The risk of recurrence of CIN3 was also reduced in patients who were vaccinated but uncertainty was large (three studies, 17 757 participants; 0.28, 0.01 to 6.37; I=71%, τ=1.23). Evidence of benefit was lacking for recurrence of vulvar, vaginal, and anal intraepithelial neoplasia, genital warts, and persistent and incident HPV infections, although the number of studies and participants in each outcome was low.
CONCLUSION
HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision. GRADE assessment for the quality of evidence indicated that the data were inconclusive. Large scale, high quality randomised controlled trials are required to establish the level of effectiveness and cost of HPV vaccination in women undergoing treatment for diseases related to HPV infection.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021237350.
Topics: Alphapapillomavirus; Female; Human papillomavirus 16; Humans; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Vaccination; Uterine Cervical Dysplasia
PubMed: 35922074
DOI: 10.1136/bmj-2022-070135 -
Annals of Oncology : Official Journal... Feb 2020Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical... (Meta-Analysis)
Meta-Analysis
Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature.
BACKGROUND
Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population.
MATERIALS AND METHODS
Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment.
DATA SYNTHESIS
Summary effects were estimated using random-effects models.
OUTCOMES
Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population.
RESULTS
Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22-69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57-4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58-21.10; P < 0.001), vulvar (3.34, 2.39-4.67; P < 0.001), and anal cancer (5.11, 2.73-9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69-36.94; P = 0.073).
CONCLUSIONS
Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.
Topics: Alphapapillomavirus; Female; Humans; Incidence; Middle Aged; Papillomavirus Infections; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 31959338
DOI: 10.1016/j.annonc.2019.11.004 -
Gynecologic Oncology Research and... 2017Merkel cell carcinoma is a rare and aggressive neoplasm originating from mechanoreceptor Merkel cells of the stratum basale of the epidermis. Cases affecting the vulva... (Review)
Review
BACKGROUND
Merkel cell carcinoma is a rare and aggressive neoplasm originating from mechanoreceptor Merkel cells of the stratum basale of the epidermis. Cases affecting the vulva are exceedingly rare, with the currently available literature primarily in case report form.
BODY
Systematic review of the PubMed database returned 17 cases of Merkel cell carcinoma affecting the vulva. Patients presented at a mean age of 59.6 years with a firm, mobile vulvar mass. Symptoms of pain, erythema, pruritus, edema, and ulceration have been reported. Tumor histology is consistent with that of neuroendocrine tumors and typical Merkel cell carcinomas. Neuroendocrine and cytokeratin immunostains are frequently utilized in histopathological workup. Surgical management was the unanimous first-line therapy with adjuvant radiation in most cases. Recurrence occurred in 70.6% of patients at a mean follow-up of 6.3 months. Mortality was at 47.0% at a mean of 7.8 months after initial operation.
CONCLUSION
Merkel cell carcinoma affecting the vulva is an extremely rare and highly aggressive neoplasm. The present review of published cases serves to comprehensively describe the clinical course and treatment approaches for vulvar Merkel cell carcinoma.
PubMed: 28138393
DOI: 10.1186/s40661-017-0037-x -
The Cochrane Database of Systematic... Feb 2014Cancer is a leading cause of death worldwide. Gynaecological cancers (i.e. cancers affecting the ovaries, uterus, cervix, vulva and vagina) are among the most common... (Review)
Review
BACKGROUND
Cancer is a leading cause of death worldwide. Gynaecological cancers (i.e. cancers affecting the ovaries, uterus, cervix, vulva and vagina) are among the most common cancers in women. Unfortunately, given the nature of the disease, cancer can recur or progress in some patients. Although the management of early-stage cancers is relatively straightforward, with lower associated morbidity and mortality, the surgical management of advanced and recurrent cancers (including persistent or progressive cancers) is significantly more complicated, often requiring very extensive procedures. Pelvic exenterative surgery involves removal of some or all of the pelvic organs. Exenterative surgery for persistent or recurrent cancer after initial treatment is difficult and is usually associated with significant perioperative morbidity and mortality. However, it provides women with a chance of cure that otherwise may not be possible. In carefully selected patients, it may also have a place in palliation of symptoms. The biology of recurrent ovarian cancer differs from that of other gynaecological cancers; it is often responsive to chemotherapy and is not included in this review.
OBJECTIVES
To evaluate the effectiveness and safety of exenterative surgery versus other treatment modalities for women with recurrent gynaecological cancer, excluding recurrent ovarian cancer (this is covered in a separate review).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to February 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of clinical guidelines and review articles and contacted experts in the field.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or non-randomised studies with concurrent comparison groups that included multivariate analyses of exenterative surgery versus medical management in women with recurrent gynaecological malignancies.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No studies were found; therefore no data were analysed.
MAIN RESULTS
The search strategy identified 1311 unique references, of which seven were retrieved in full, as they appeared to be potentially relevant on the basis of title and abstract. However, all were excluded, as they did not meet the inclusion criteria of the review.
AUTHORS' CONCLUSIONS
We found no evidence to inform decisions about exenterative surgery for women with recurrent cervical, endometrial, vaginal or vulvar malignancies. Ideally, a large RCT or, at the very least, well-designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances are needed to compare exenterative surgery versus medical management, including palliative care.
Topics: Adult; Female; Genital Neoplasms, Female; Humans; Neoplasm Recurrence, Local; Pelvic Exenteration
PubMed: 24497188
DOI: 10.1002/14651858.CD010449.pub2 -
Cancers Mar 2023Vulvar Paget's disease (VPD) is a rare form of cutaneous adenocarcinoma of the vulva, which accounts for about 1-2% of all vulvar neoplasms and mainly affects... (Review)
Review
Vulvar Paget's disease (VPD) is a rare form of cutaneous adenocarcinoma of the vulva, which accounts for about 1-2% of all vulvar neoplasms and mainly affects post-menopausal women. The clinical presentation is usually non-specific and mimics chronic erythematous skin lesions; therefore, the diagnosis is often difficult and delayed. Although VPD is typically diagnosed at a locally advanced stage and has a high recurrence rate, the prognosis is overall favorable with a 5-year survival of nearly 90%. Due to the limited and poor-quality evidence, there is no global consensus on optimal management. Therefore, we performed a systematic review of the literature through the main electronic databases to deepen the current knowledge of this rare disease and discuss the available treatment strategies. Wide surgical excision is recommended as the standard-of-care treatment and should be tailored to the tumor position/extension and the patient's performance status. The goal is to completely remove the tumor and achieve clear margins, thus reducing the rate of local recurrences. Non-surgical treatments, such as radiotherapy, chemotherapy, and topical approaches, can be considered, especially in the case of unresectable and recurrent disease. In the absence of clear recommendations, the decision-making process should be individualized, also considering the new emerging molecular targets, such as HER2 and PD-L1, which might pave the way for future targeted therapies. The current review aims to raise awareness of this rare disease and encourage international collaboration to collect larger-scale, high-quality evidence and standardize treatment.
PubMed: 36980691
DOI: 10.3390/cancers15061803 -
The interplay of HIV and human papillomavirus-related cancers in sub-Saharan Africa: scoping review.Systematic Reviews Apr 2020People living with HIV (PLHIV) are at a high risk of developing HPV-related cancers. HPV-related malignancies occur frequently and/or are high among PLHIV, with cervical... (Review)
Review
BACKGROUND
People living with HIV (PLHIV) are at a high risk of developing HPV-related cancers. HPV-related malignancies occur frequently and/or are high among PLHIV, with cervical cancer as a designated AIDS-defining condition. We aimed to explore the evidence on the interplay of HIV and HPV-related cancers in sub-Saharan Africa (SSA).
METHODS
The scoping review was guided by Arksey and O'Malley's framework. We searched for literature from the following databases: PubMed; World Health Organization (WHO) Library; Science Direct; Google Scholar and EBSCOhost (Academic search complete, Health Source: Nursing/Academic Edition, CINAHL). Studies reporting on evidence HIV and HPV-related cancers interplay in SSA were eligible for inclusion in this review. The Mixed Methods Appraisal Tool (MMAT) tool was used to assess the risk of bias of the included studies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used for reporting the search results. Thematic analysis used to reveal the emerging themes from the included studies.
RESULTS
A total of 74 potentially eligible articles were screened. Of these, nine (7 reviews, 1 transversal case controls, and 1 quantitative study) were eligible for data extraction. The studies reported about a total of 16,351 participants in different settings. The nine included studies showed evidence of cervical cancer among HIV-infected women and distribution of HPV infection and cervical abnormalities among HIV-positive individuals. In the four studies generalizing about HIV and anal cancer, only one reported about HPV. Two studies generally reported about HIV and head and neck cancers and one reported about interaction of HIV with vaginal cancer, vulvar cancer, and penile cancer, respectively.
CONCLUSION
HIV positivity is associated with increased prevalence of HPV infection on different anatomic sites, which will result in increased burden of HPV-related cancers among PLHIV. Furthermore, primary studies with robust study designs aimed at investigating the risk developing HPV-related cancers among PLHIV are recommended. Systematic review registration: PROSPERO CRD42017062403.
Topics: Africa South of the Sahara; Alphapapillomavirus; Female; HIV Infections; Humans; Neoplasms; Papillomaviridae; Papillomavirus Infections
PubMed: 32321580
DOI: 10.1186/s13643-020-01354-1 -
International Journal of Cancer Sep 2017In this updated systematic review and meta-analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell... (Meta-Analysis)
Meta-Analysis Review
In this updated systematic review and meta-analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase and Cochrane Library databases were used to identify studies published between 1990 and 2015 and using a PCR-based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model. The I statistic was used to describe the amount of heterogeneity. In meta-regression analyses, potential sources of heterogeneity were evaluated. We identified 92 eligible papers, comprising altogether 5,015 cases of vulvar cancer (64 papers) and 2,764 cases of VIN (48 papers). The pooled prevalence of HPV in vulvar cancer was 39.7% (95% CI: 35.1-44.4%). Overall, 76.3% (95% CI: 70.1-82.1%) of VIN lesions tested HPV-positive, while the HPV prevalence in new subcategories of VIN, uVIN and dVIN, was 86.2% (95% CI: 73.5-95.5%) and 2.0% (95% CI: 0-10.0%), respectively. Substantial between-study heterogeneity was observed (vulvar cancer: I = 88.4%; VIN: I = 90.7%) with the largest variation between geographical regions. Among HPV-positive cases, the predominant high-risk HPV type was HPV16, followed by HPV33 and HPV18. HPV6 was detected as a single infection in a small subset of VIN and vulvar cancer samples. Thus, HPV vaccination targeting these HPV types may prevent a substantial number of vulvar lesions.
Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; DNA, Viral; Europe; Female; Genotype; Humans; North America; Papillomaviridae; Papillomavirus Infections; Prevalence; Vulvar Neoplasms
PubMed: 28577297
DOI: 10.1002/ijc.30821 -
The Cochrane Database of Systematic... Mar 2014This 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... (Review)
Review
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.
Topics: Adult; Carcinoma in Situ; Female; Humans; Lasers, Gas; Precancerous Conditions; Randomized Controlled Trials as Topic; Suction; Ultrasonic Therapy; Vulvar Neoplasms
PubMed: 24596022
DOI: 10.1002/14651858.CD007928.pub3 -
International Urogynecology Journal Apr 2018Pelvic floor disorders (PFDs) negatively affect quality of life in the general population, and their prevalence in gynecologic cancer survivors has not been... (Review)
Review
INTRODUCTION AND HYPOTHESIS
Pelvic floor disorders (PFDs) negatively affect quality of life in the general population, and their prevalence in gynecologic cancer survivors has not been systematically described. This study aimed to determine the prevalence of PFDs in cancer survivors. We hypothesized that the prevalence of PFDs in the gynecologic cancer population would be higher than in the general female population.
METHODS
We searched PubMed (1809 to present), EMBASE (1974 to present), and the Cochrane Central Register of Controlled Trials (CENTRAL) through May 2017. The search combined subject headings, title, and abstract words for gynecologic cancer, PFDs, and prevalence. Any studies evaluating the prevalence of PFDs in gynecologic malignancies were included.
RESULTS
A total of 550 articles met the designated search criteria and 31 articles were included in this review. In cervical cancer survivors, before treatment the prevalences of stress urinary incontinence (SUI), urgency urinary incontinence (UUI) and fecal incontinence (FI) were 24-29%, 8-18% and 6%, respectively, and after treatment the prevalences of SUI, UUI, urinary retention, FI, fecal urge, dyspareunia and vaginal dryness were 4-76%, 4-59%, 0.4-39%, 2-34%, 3-49%, 12-58% and 15-47%, respectively. In uterine cancer survivors, before treatment the prevalences of SUI, UUI and FI were 29-36%, 15-25% and 3%, respectively, and after treatment the prevalences of urinary incontinence (UI) and dyspareunia were 2-44% and 7-39%, respectively. In vulvar cancer survivors, after treatment the prevalences of UI, SUI and FI were 4-32%, 6-20% and 1-20%, respectively. In ovarian cancer survivors, the prevalences of SUI, UUI, prolapse and sexual dysfunction were 32-42%, 15-39%, 17% and 62-75%, respectively.
CONCLUSIONS
PFDs are prevalent in gynecologic cancer survivors and this is an important area of clinical concern and future research.
Topics: Cancer Survivors; Female; Genital Neoplasms, Female; Humans; Pelvic Floor Disorders; Prevalence
PubMed: 28929201
DOI: 10.1007/s00192-017-3467-4 -
International Journal of Molecular... Nov 2017In recent years, a vast amount of studies have centered on the role of vitamin D in the pathogenesis of certain types of cancers such as breast, colorectal and lung... (Review)
Review
In recent years, a vast amount of studies have centered on the role of vitamin D in the pathogenesis of certain types of cancers such as breast, colorectal and lung cancer. Increasing evidence suggests that vitamin D and its receptor play a crucial role in the development of gynecological cancers. In this review, we systematically analyzed the effect of vitamin D and the vitamin D receptor on endometrial, ovarian, cervical, vulvar and vaginal cancer. Our literature research shows that vitamin D levels and vitamin-D-related pathways affect the risk of gynecological cancers. Numerous ecological studies give evidence on the inverse relationship between UVB exposure and gynecological cancer risk. However, epidemiologic research is still inconclusive for endometrial and ovarian cancer and insufficient for rarer types of gynecological cancers. The vitamin D receptor (VDR) is upregulated in all gynecological cancers, indicating its influence on cancer etiology. The VDR polymorphism FokI (rs2228570) seems to increase the risk of ovarian cancer. Other nuclear receptors, such as the RXR, also influence gynecological cancers. Although there is limited knowledge on the role of the VDR/RXR on the survival of endometrial, cervical, vulvar or vaginal cancer patients, some studies showed that both receptors influence survival. Therefore, we suggest that further studies should focus on the vitamin D- and its hetero dimer receptor RXR in gynecological cancers.
Topics: Biomarkers, Tumor; Female; Genital Neoplasms, Female; Humans; Polymorphism, Genetic; Receptors, Calcitriol; Up-Regulation; Vitamin D
PubMed: 29113037
DOI: 10.3390/ijms18112328