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Acta Obstetricia Et Gynecologica... Jan 2024Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways-one involving high-risk human papilloma virus infection (HPV-associated), and the...
INTRODUCTION
Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways-one involving high-risk human papilloma virus infection (HPV-associated), and the other without HPV infection (HPV-independent) often involving TP53 mutation. HPV-associated VSCC generally has a better progression-free survival than HPV-independent VSCC. The aim of this study was to determine TP53 mutation status using immunohistochemistry, compare different methods of HPV detection and correlate both with survival in a retrospective cohort of 123 patients with VSCC.
MATERIAL AND METHODS
Immunohistochemistry for p53, Ki67 and p16 (a surrogate marker for HPV infection) was performed on formalin-fixed paraffin-embedded tissues from a cohort of surgically treated VSCC patients to identify molecular subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR and HPV mRNA in situ hybridization (ISH). The Pearson chi-square test and multivariable Cox regression model were used to investigate the association of different parameters with progression-free survival and disease-specific survival (DSS), and Kaplan-Meier curves were used to show the association of different parameters with survival.
RESULTS
The results of p53 and p16 immunohistochemistry confirmed three VSCC subtypes associated with different prognosis. The TP53 mutation status was identified as an independent prognostic factor of worse progression-free survival (p = 0.024) after adjustment for FIGO stage. p16 immunohistochemistry, mRNA ISH, and DNA PCR had excellent concordance in terms of HPV detection. According to the multivariable Cox regression model, the presence of hrHPV mRNA correlated significantly with increased progression-free survival (p = 0.040) and DSS (p = 0.045), after adjustment for other confounders.
CONCLUSIONS
p53 and p16 immunohistochemistry stratify VSCC cohort into three subtypes with TP53mutated patients having the worst prognosis. The detection of hrHPV mRNA by ISH was an independent predictor of increased survival. Thus, the combined detection of p53 and HPV mRNA might improve risk stratification in VSCC.
Topics: Female; Humans; Prognosis; Human Papillomavirus Viruses; Papillomavirus Infections; Retrospective Studies; Cyclin-Dependent Kinase Inhibitor p16; Tumor Suppressor Protein p53; Carcinoma, Squamous Cell; Vulvar Neoplasms; DNA; RNA, Messenger; Vulva; Papillomaviridae
PubMed: 37840151
DOI: 10.1111/aogs.14689 -
Acta Obstetricia Et Gynecologica... Apr 2024Gynecological cancer diagnosed during pregnancy requires accurate diagnosis and staging to determine optimal treatment based on gestational age. Cervical and ovarian...
Gynecological cancer diagnosed during pregnancy requires accurate diagnosis and staging to determine optimal treatment based on gestational age. Cervical and ovarian cancers are the most common and multidisciplinary team collaboration is pivotal. Magnetic resonance imaging and ultrasound can be used without causing fetal harm. In cervical cancer, early-stage treatments can often be delayed until fetal lung maturation and cesarean section is recommended if disease prevails, in combination with a simple/radical hysterectomy and lymphadenectomy. Chemoradiotherapy, the recommended treatment for advanced stages, is not compatible with pregnancy preservation. Most gestational ovarian cancers are diagnosed at an early stage and consist of nonepithelial cancers or borderline tumors. Removal of the affected adnexa during pregnancy is often necessary for diagnosis, though staging can be performed after delivery. In selected cases of advanced cervical and ovarian cancers, neoadjuvant chemotherapy may be an option to allow gestational advancement but only after thorough multidisciplinary discussions and counseling.
Topics: Pregnancy; Female; Humans; Cesarean Section; Uterine Cervical Neoplasms; Genital Neoplasms, Female; Ovarian Neoplasms; Lymph Node Excision; Pregnancy Complications, Neoplastic; Neoplasm Staging; Hysterectomy
PubMed: 38183316
DOI: 10.1111/aogs.14763 -
Cancer Control : Journal of the Moffitt... 2024The human papillomavirus (HPV) is a typical sexually transmitted disease that affects different epithelial cells and can cause a number of health problems. HPV is mainly...
The human papillomavirus (HPV) is a typical sexually transmitted disease that affects different epithelial cells and can cause a number of health problems. HPV is mainly spread through sexual contact and is extremely contagious, even in the absence of obvious symptoms. It is linked to a number of malignancies, such as oropharyngeal, cervical, anal, vulvar, vaginal, and cutaneous as well as anogenital and cutaneous warts. Different vaccines targeting various HPV virus strains have been produced to prevent HPV infections. Vaccines can help prevent HPV-related illnesses, but they cannot cure malignancies that have already been caused by HPV. But new developments in mRNA vaccines have shown potential in combating malignancies linked to HPV. mRNA vaccines stimulate the immune system to identify and attack particular proteins present in viruses or tumour cells. The efficacy of mRNA vaccines in preventing HPV-related malignancies has been shown in preliminary experiments in mice. Additionally, in clinical trials aimed at individuals with HPV-related head and neck malignancies, personalised mRNA vaccines in combination with immune checkpoint drugs have demonstrated encouraging results. Even though mRNA vaccines have drawbacks and restrictions such as immunogenicity and instability, further research and development in this area has a great deal of promise for developing effective therapies for HPV-related malignancies.
Topics: Female; Humans; Animals; Mice; Papillomavirus Infections; mRNA Vaccines; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Papillomavirus Vaccines
PubMed: 38462683
DOI: 10.1177/10732748241238629 -
Tidsskrift For Den Norske Laegeforening... Jun 2024Vulvar leiomyoma is rare and is often misdiagnosed as a cyst or abscess in the Bartholin's glands. Other causes of benign tumours of the vulva are Gartner's duct cysts,...
Vulvar leiomyoma is rare and is often misdiagnosed as a cyst or abscess in the Bartholin's glands. Other causes of benign tumours of the vulva are Gartner's duct cysts, fibromas, fibroadenomas, lipomas and hamartomas. Adenoma was the tentative diagnosis is this case history, but the histology showed a benign leiomyoma.
Topics: Humans; Female; Vulvar Neoplasms; Leiomyoma; Adult; Middle Aged; Diagnosis, Differential
PubMed: 38934324
DOI: 10.4045/tidsskr.23.0818 -
Critical Reviews in Oncology/hematology Jan 2024Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their... (Review)
Review
Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients' age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.
Topics: Female; Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Vulvar Neoplasms; Neoplasm Staging; Vulva; Neuroendocrine Tumors; Lymph Node Excision
PubMed: 37977312
DOI: 10.1016/j.critrevonc.2023.104201 -
Cancers Mar 2024Aggressive angiomyxoma (AAM) is a rare, locally aggressive, myxoid mesenchymal neoplasm primarily found in the pelvic and perineal regions of young adult females. It is... (Review)
Review
Aggressive angiomyxoma (AAM) is a rare, locally aggressive, myxoid mesenchymal neoplasm primarily found in the pelvic and perineal regions of young adult females. It is a slow growing and locally infiltrating tumor. Preoperative diagnosis is difficult due to the rarity of these tumors and absence of characteristic signs and symptoms. The primary management is tumor excision. Incomplete excision is common because of the infiltrating nature of the neoplasm and absence of a definite capsule. Other non- surgical modalities have been employed, such as radiotherapy, embolization, GnRH analogues or other anti-estrogenic agents. Local relapses occur in 30-40% of the cases, and often appear many years (sometimes decades) after the first excision. Occasional distant metastasis has also been reported. A limited number of cases have been reported in the literature, mostly in the form of small case series or isolated case reports. Therefore, the aim of this paper by a team of experts from the MITO rare tumors group is to review clinical findings, pathologic characteristics and outcome of patients affected by this rare condition in order to be able to offer up-to-date guidance on the management of these cases.
PubMed: 38611053
DOI: 10.3390/cancers16071375 -
PloS One 2023Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that...
Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that MOGS would display unique miR and mRNA expression profiles. The miR and mRNA expression profile in RNA from formalin fixed, paraffin embedded vaginal melanomas (relative to vaginal mucosa) and vulvar melanomas (relative to cutaneous melanoma) were measured with the Nanostring Human miRNA assay and Tumor Signaling mRNA assay. Differential patterns of expression were identified for 21 miRs in vaginal and 47 miRs in vulvar melanoma (fold change >2, p<0.01). In vaginal melanoma, miR-145-5p (tumor suppressor targeting TLR4, NRAS) was downregulated and miR-106a-5p, miR-17-5p, miR-20b-5p (members of miR-17-92 cluster) were upregulated. In vulvar melanoma, known tumor suppressors miR-200b-3p and miR-200a-3p were downregulated, and miR-20a-5p and miR-19b-3p, from the miR-17-92 cluster, were upregulated. Pathway analysis showed an enrichment of "proteoglycans in cancer". Among differentially expressed mRNAs, topoisomerase IIα (TOP2A) was upregulated in both MOGS. Gene targets of dysregulated miRs were identified using publicly available databases and Pearson correlations. In vaginal melanoma, suppressor of cytokine signaling 3 (SOCS3) was downregulated, was a validated target of miR-19b-3p and miR-20a-5p and trended toward a significant inverse Pearson correlation with miR-19b-3p (p = 0.093). In vulvar melanoma, cyclin dependent kinase inhibitor 1A (CDKN1A) was downregulated, was the validated target of 22 upregulated miRs, and had a significant inverse Pearson correlation with miR-503-5p, miR-130a-3p, and miR-20a-5p (0.005 < p < 0.026). These findings support microRNAs as mediators of gene expression in MOGS.
Topics: Humans; Female; Melanoma; Skin Neoplasms; MicroRNAs; Genes, cdc; Vulvar Neoplasms; Suppressor of Cytokine Signaling Proteins
PubMed: 37384650
DOI: 10.1371/journal.pone.0285804 -
Journal of Obstetrics and Gynaecology :... Dec 2023Inguinal lymph node involvement is the most robust predictor of mortality in vulval cancer and sentinel lymph node (SLN) biopsy is a safe diagnostic modality. We...
Sentinel lymph node biopsy based on anatomical landmarks and locoregional mapping of inguinofemoral sentinel lymph nodes in women with vulval cancer: an operative technique.
Inguinal lymph node involvement is the most robust predictor of mortality in vulval cancer and sentinel lymph node (SLN) biopsy is a safe diagnostic modality. We describe a technique based on anatomical landmarks. Our aims are (1) to describe the territorial mapping of SLNs, (2) to evaluate the associated complication rate vis-à-vis those reported in the literature, and (3) to assess its accuracy in detecting SLNs. Data from women who underwent groin SLN biopsies for vulval cancer at a single cancer centre were prospectively collected. All subjects met the GROINSS-V eligibility criteria. The location of the SLN relative to the saphenous vein was recorded. All women were followed up and early and late complications were recorded. The recurrence rate at the time of the census was calculated. A total of 71 groins in 44 women were included. The SLN was primarily located over Cloquet's node (85.2%). The incidence of early wound cellulitis and dehiscence were 2.8% and 11.3% while lymphocysts were present in 11.3% of groins. The negative nodal recurrence rate was 1.7%. Results showed that this reproducible technique allows access to 96.7% of SLNs, including both deep and superficial SLNs whilst minimising the need for extensive dissection and complications associated with overharvesting of lymph nodes.
Topics: Female; Humans; Sentinel Lymph Node Biopsy; Sentinel Lymph Node; Lymph Node Excision; Lymphatic Metastasis; Lymph Nodes; Vulvar Neoplasms; Neoplasm Staging
PubMed: 37170959
DOI: 10.1080/01443615.2023.2207205 -
In Vivo (Athens, Greece) 2023Data regarding the clinicopathological factors predicting recurrence and prognosis in patients with vulvar extramammary Paget disease (VPD) are limited. Therefore, we... (Review)
Review
BACKGROUND/AIM
Data regarding the clinicopathological factors predicting recurrence and prognosis in patients with vulvar extramammary Paget disease (VPD) are limited. Therefore, we aimed to identify predictive factors for recurrence and outcomes in patients with VPD.
PATIENTS AND METHODS
Forty-five patients with VPD were included in this study. We reviewed electronic medical records and pathology slides to collect clinicopathological information.
RESULTS
Eighteen cases (40.0%) had resection margin (RM) involvement. Twelve patients (26.7%) received adjuvant radiation therapy (RT). Ten patients (22.2%) experienced recurrence. The recurrence rate was higher in patients who underwent wide local excision or simple vulvectomy than in those who underwent radical vulvectomy. Positive RM involvement was a significant and independent predictive factor for worse recurrence-free survival (RFS). The overall survival rate of patients who received adjuvant RT was significantly higher than that of those who underwent surgery alone.
CONCLUSION
A positive RM involvement independently predicted worse RFS. The recurrence rate was significantly associated with the type of surgical procedure performed. Additionally, adjuvant RT can improve the prognosis of patients with VPD.
Topics: Female; Humans; Paget Disease, Extramammary; Vulvar Neoplasms; Prognosis; Gynecologic Surgical Procedures; Margins of Excision; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 37905666
DOI: 10.21873/invivo.13369 -
Techniques in Coloproctology Jan 2024In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to... (Review)
Review
In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to persistent HPV16 infection. Invasive cancer is preceded by precancerous lesions. In addition to patients with a personal history of precancerous lesions and anal cancer, three groups are at very high risk of anal cancer: (i) men who have sex with men and are living with HIV, (ii) women with a history of high-grade squamous intraepithelial lesions (HSILs) or vulvar HPV cancer, and (iii) women who received a solid organ transplant more than 10 years ago. The purpose of screening is to detect HSILs so that they can be treated, thereby reducing the risk of progression to cancer. All patients with symptoms should undergo a proctological examination including standard anoscopy. For asymptomatic patients at risk, an initial HPV16 test makes it possible to target patients at risk of HSILs likely to progress to cancer. Anal cytology is a sensitive test for HSIL detection. Its sensitivity is greater than 80% and exceeds that of proctological examination with standard anoscopy. It is indicated in the event of a positive HPV16 test. In the presence of cytological abnormalities and/or lesions and a suspicion of dysplasia on clinical examination, high-resolution anoscopy is indicated. Performance is superior to that of proctological examination with standard anoscopy. However, this technique is not widely available, which limits its use. If high-resolution anoscopy is not possible, screening by a standard proctological examination is an alternative. There is a need to develop high-resolution anoscopy and triage tests and to evaluate screening strategies.
Topics: Male; Humans; Female; Human Papillomavirus Viruses; Homosexuality, Male; Sexual and Gender Minorities; Precancerous Conditions; Anus Neoplasms
PubMed: 38198036
DOI: 10.1007/s10151-023-02899-8