Vaginal Tumors Research Articles

Individual curved-needle interstitial template created using three-dimensional printing for brachytherapy for distal parauterine tumor recurrence.

Achieving a clinically acceptable dose distribution with commercial vaginal applicators for brachytherapy of recurrent parauterine tumors is challenging. However, the application of three-dimensional (3D) printing technology in brachytherapy has been widely acknowledged and can improve clinical treatment outcomes. This study aimed to introduce an individual curved-needle interstitial template (ICIT) created using 3D printing technology for high-dose-rate (HDR) brachytherapy with interstitial treatment to provide a clinically feasible approach to distal parauterine and vaginal cuff tumors. The entire workflow, including the design, optimization, and application, is presented. Ten patients with pelvic cancer recurrence were examined at our center. The vaginal topography was filled with gauze strips soaked in developer solution, and images were obtained using computed tomography (CT) and magnetic resonance imaging (MRI). Curved needle paths were designed, and ICITs were 3D-printed according to the high-risk clinical target volume (HRCTV) and vaginal filling model. The dose and volume histogram parameters of the HRCTV (V100, V200, D90, and D98) and organs at risk (OARs) (D2cc) were recorded. All patients completed interstitial brachytherapy treatment with the 3D-printed ICIT. One patient experienced vaginal cuff tumor recurrence, and nine patients experienced parametrial tumor recurrence (four on the left and five on the right). We used two to five interstitial needles, and the maximum angle of the curved needle was 40°. No source obstruction events occurred during treatment of these 10 patients. The doses delivered to the targets and OARs of all patients were within the dose limits and based on clinical experience at our center. The ICIT is a treatment option for patients with distal parauterine tumor recurrence. This method addresses the limitations of vaginal intracavitary and standard interstitial applicators. The ICIT has the advantages of biocompatibility, personalization, and magnetic resonance imaging compatibility.

Vaginal and vulvar tumors

Vaginal and vulvar tumors

Giant Endocervical Polyp with Malignant Characteristics in an Adolescent

Introduction: A cervical polyp is a flexible, friable, pedunculated neoplasm, mostly originating from the endocervical area. It is considered giant when it is >4 cm. Most are benign but they must be removed and subjected to histopathologic examination because they may present malignancy. Clinical Case: A 13-year-old female patient, with no personal pathological personal or familiar history, was referred from another health center due to a 1-year history of a vaginal tumor with apparently no underlying cause. Physical examination showed a red, multilobulated, vaginal tumor of approximately 10 cm long, with mucus around it, foul-smelling, easy bleeding, painful on palpation, protruding from vaginal introitus with a deep pedicle. The patient underwent surgery where the excision of the vaginal tumor extending to the exocervix was performed. Conclusion: In this case, due to the initial clinical characteristics, a malignant pathology (such as rhabdomyosarcoma) may be suspected, thus, complementary imaging and laboratory studies need to be performed, to rule out this diagnosis and offer an adequate and well oriented surgical treatment; a subsequent definitive histopathological study needs to be conducted to confirm that the lesion is compatible with an endocervical polyp, determining the patients prognosis and follow-up requirements.

Vaginal Rhabdomyosarcome: Case Report

Introduction: Rhabdomyosarcoma is a soft tissue sarcoma, most common in children, localised in the female genital tract and therefore rare in adults. Among its subtypes, it is most often distinguished as embryonal. It is an aggressive tumour, difficult to diagnose, is usually detected by CT or MRI and the diagnosis is confirmed by biopsy and treatment involving surgical excision, radiotherapy and chemotherapy. The authors present a case of embryonal rhabdomyosarcoma localised in the vagina, highlighting relevant aspects of the subject. Observation: We report the observation of a girl aged 2 years and 8 months, with no notable antecedents, from a 2nd degree consanguineous marriage. For 1 month she presented with a rapidly progressive vaginal mass associated with bleeding. Examination revealed a reddish, grape-like mass in the vulva. Abdomino-pelvic ultrasound revealed a vaginal tumour, abdomino-pelvic MRI revealed an endovaginal mass delivered through the vulva, suggesting a botryoid rhabdomyosarcoma, and biopsy of the vaginal mass with morphological appearance and immunohistochemical profile of an embryonal rhabdomyosarcoma. The extension work-up showed a vulvovaginal lesional process, with no secondary location on the thoraco-abdominal CT scan. The patient was classified as group C according to the RMS 2005 protocol and received 6 courses of IVA + vaginal brachytherapy + 3 courses of IVA with a good clinical and biological evolution. Conclusion: In view of the diagnostic difficulties and the risk of progression and rapid worsening of rhabdomyosarcoma, early positive diagnosis means that treatment can be started at an early stage with chemotherapy, surgery and radiotherapy.

Imaging of Vaginal Yolk Sac Tumor: 2 Case Reports and Literature Review

Our article reports on two cases of pediatric vaginal yolk sac tumors (YSTs), underscoring the diagnostic challenges posed by their similarities to other vaginal tumors, particularly in differentiating from embryonal rhabdomyosarcoma based on clinical and radiological presentations. Emphasizing the critical role of MRI, histological examination, and alpha-fetoprotein levels in diagnosis, we highlight the complexities of treatment, which has evolved from radical surgeries to more conservative approaches with adjuvant chemotherapy, aiming to preserve future sexual and reproductive functions. Our findings advocate for individualized treatment plans and stress the importance of accurate diagnosis and the potential need for alternative therapeutic strategies in cases of atypical response to treatment.

Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report

BackgroundThe risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids.Case presentationThis study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge.ConclusionsWhen observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.

Early diagnosis and appropriate management of vaginal leiomyoma in rural areas

HIGHLIGHTS Extrauterine leiomyoma, including vaginal leiomyoma, is an exceedingly rare condition with complex pathogenesis and management Clinical evaluation and high-quality imaging are required to confirm the diagnosis of vaginal tumor. If there are insufficient facilities, referrals must be made. Operative management using vaginal approach was described for treating vaginal leiomyoma. ABSTRACT Objective: To describe the challenges of early diagnosis and appropriate management of vaginal leiomyoma in rural areas. Case Report: A 26-year-old woman, P1A0, was referred from a rural hospital and presented a chief complaint of vaginal mass. The patient was admitted to the tertiary hospital with suspected malignant vaginal tumor and underwent a biopsy, which revealed leiomyoma on pathological examination. Despite conservative treatment, the mass continued to grow, unaffected by the menstrual cycle, causing discomfort. Following a second hospital admission, the patient underwent surgical management of extirpation and vaginal reconstruction. The microscopic finding of the tumor showed myositis cell proliferation with hyperplastic growth, monotonous nuclei, and variable cell shapes, supporting the diagnosis of vaginal leiomyoma. During postoperative monitoring, there was no vaginal bleeding. Thereafter, on the day following surgery, it was found that the right labium major was swollen. This was treated with anticoagulants, topical NSAIDs, and a sitz bath. The patient was discharged from the hospital in good condition and had an uneventful postoperative recovery. Conclusion: Although the incidence of vaginal leiomyoma is uncommon, precise early diagnosis and appropriate management might improve outcomes, particularly in rural areas.

The Validity of Immunohistochemistry in Detecting Microsatellite Instability in Pediatric Solid Neoplasms

Abstract Background: The DNA mismatch repair (MMR) is the biological pathway that plays a key role in maintaining genomic stability during DNA replication and recombination. The value of MMR pathway is under investigation in pediatrics’ solid tumors. Aims: In this research work, we investigated the proteins involved in the oncogenesis of pediatric solid neoplasms and detect these proteins in a representative cohort sample of Saudi pediatric cases under the bioinformatic networking technique. We also described the MLH1, BRAF, p53, proliferating cell nuclear antigen, and PMS2 along with MSH2-MSH6 antibodies to be a diagnostic immunohistochemistry (IHC) panel for identifying MMR mutations. This research will open the new doors for advanced research on proteins involved in the oncogenesis of pediatric solid neoplasms. The hypotheses were tested on a sample of solid malignancies and IHC results were reported. Material and Methods: The study was conducted in different institutions in Saudi Arabia. The inclusion criteria required enrolling biopsies of solid neoplasms or resected solid malignant neoplasms presented to the laboratories in the participating institutions of all pediatric patients (aging from 0 to 14 years). The specimens were examined microscopically utilizing Hematoxylin and Eosin stain as well as the utilization of MMR proteins immunohistochemistry (IHC), and PNCA. Results: The qualitative assessment showed that IHC diagnosis yielded positive results with ≥80% of positive cells (intact) for MMR proteins (MSH2, MSH6, PMS2, and MLH1). The PCNA protein was absent only in vaginal germ cell tumor and metastatic medulloblastoma. Conclusion: In our sample, we have found that there is an intact MMR proteins expression. Also, the IHC technique presents accuracy and ability as a diagnostic technique for identifying the different types of pediatric cancers. The MMR protein panel accompanied with PCNA panels holds additional value, as it helps reduce dependency solely on MMR protein expressions.

Immunity from NK Cell Subsets Is Important for Vaccine-Mediated Protection in HPV+ Cancers.

High-risk human papillomaviruses (HPVs) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing in the USA and worldwide. Survival rates for patients with locally advanced disease are poor after standard-of-care chemoradiation treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential. We reported earlier that in a syngeneic immunocompetent preclinical HPV tumor mouse model, intranasal immunization with an HPV peptide therapeutic vaccine containing the combination of aGalCer and CpG-ODN adjuvants (TVAC) promoted clearance of HPV vaginal tumors via induction of a strong cytotoxic T cell response. However, TVAC was insufficient in the clearance of HPV oral tumors. To overcome this deficiency, we tested substituting aGalCer with a clinically relevant adjuvant QS21 (TVQC) and observed sustained, complete regression of over 70% of oral and 80% of vaginal HPV tumors. The TVQC-mediated protection in the oral tumor model correlated with not only strong total and HPV-antigen-specific CD8 T cells, but also natural killer dendritic cells (NKDCs), a novel subset of NK cells expressing the DC marker CD11c. Notably, we observed induction of significantly higher overall innate NK effector responses by TVQC relative to TVAC. Furthermore, in mice treated with TVQC, the frequencies of total and functional CD11c+ NK cell populations were significantly higher than the CD11c- subset, highlighting the importance of the contributions of NKDCs to the vaccine response. These results emphasize the importance of NK-mediated innate immune effector responses in total antitumor immunity to treat HPV+ cancers.

Semi-automatic design concept of 3D-printed individualized template for interstitial brachytherapy of vaginal tumors

We aimed to introduce a novel semi-automatic design approach for fabricating individualized, three-dimensional printed template dedicated to interstitial brachytherapy in vaginal tumor treatment. The central component of this concept involved the development of a cylindrical template with strategically placed tunnels to optimize applicator placement. These tunnels originated from the template's base, meticulously designed to prevent any potential overlap or interference. For precise tumor localization, we employed a method wherein the tumor's mask image was projected onto a spherical surface. Subsequently, we employed the k-means algorithm to segment the terminal points, with each cluster's center serving as the terminal point. To ensure the optimal starting point for the tunnels, we utilized the conjugate gradient method, considering the following factors: inter-starting point distance, angles between tunnels, inter-tunnel distance, and the starting point's position relative to the base of the template (inside or outside). We established a semi-automatic design paradigm for fabricating three-dimensional printed template tailored for vaginal brachytherapy. While our initial findings are promising, further comprehensive investigations are imperative to validate the clinical efficacy of this innovative concept.

Visual diagnosis of internal tumors of dogs and cats in Samarkand

In this article, is provided the importance and effectivity using visual diagnostic methods in the practice of veterinary oncology for the purpose of early diagnosis and treatment of tumors as ultrasound and X-ray and also blood morphological biochemical parameters in 15 dogs with oncological diseases of internal organs in the of canine service dogs and 2 cats belonging to the population of Samarkand region. During the research, 55 service dogs, 110 dogs under the care of the population in the regions of Samarkand and Tashkent and 123 street dogs a total of 288 dogs, as well as the clinic of the “Veterinary Surgery and Obstetrics” Department of the SamSUVM and Specialization of veterinary clinic of the National Cynology Center of Custom service in Tashkent. As a result of clinical and visual diagnosis of 56 heads of population brought to the veterinary clinic, 15 (5.3%) dogs and 2 (3.6%) cats had problems related to tumors located in various internal organs. Tumors identified were uterine and ovarian tumors in 6 (40%) dogs and 2 cats (100%), vaginal tumors in 3 (20%), liver tumors in 2 (13.3%), 1 (6.69%) tumor in stomach, 1 (6.69 %) esophagus, 2 (13.3 %) intestinal tumors were determinated.

Development and clinical implementation of simple needle attachment post placement interstitial template (SNAPP-IT) enabling a shorter, more direct needle path while preserving tumor visualization

Purpose: Historical gynecologic interstitial brachytherapy templates block direct tumor visualization during needle placement, presenting an opportunity for clinical innovation to develop a novel interstitial template allowing direct tumor visualization during needle insertion. Methods: We designed and implemented a novel interstitial template, Simple Needle Attachment Post Placement Interstitial Template (SNAPP-IT), that allowed direct visualization of the target vaginal tumor during interstitial needle placement while maintaining the ability to individually secure needles to the template, allow a vaginal cylinder, suture holes for securing to the perineum, MRI compatibility and sterilizable for repeat use. Procedure outcomes including procedure time, needle path lengths, and plan dosimetry were prospectively captured in a patient database. Results: Forty gynecologic interstitial brachytherapy cases were recorded (20 SNAPP-IT, 20 traditional templates). Needle insertion depth was reduced using the SNAPP-IT in comparison with traditional interstitial templates (11.8cm vs 3.6cm, p<0.0001). The average CTV volume was 25.6 cc for SNAPP-IT and 20.7 cc for traditional; both methods averaged a similar number of needles (15.8, 15.6). Dosimetric constraints were similarly met in both treatment groups. Procedures performed using the SNAPP-IT were shorter compared with those performed with traditional interstitial devices (83.4 minutes vs 100.7 minutes) and there were no post-operative infections in the SNAPP-IT group. Conclusion: Implementation of a novel gynecologic interstitial brachytherapy template (SNAPP-IT) reduced procedure times, allowed direct tumor visualization, and decreased needle insertion depth. SNAPP-IT provides a useful alternative approach for vaginal interstitial brachytherapy, may increase brachytherapist efficiency with complex procedures and potentially expands access to interstitial brachytherapy.

Medical Imaging of Women Diseases and Abnormalities Annulling the Marriage and its Treatment and the Impact on Shagging Annulment

This study has addressed the women’s demerits and abnormalities that Fuqaha’ mentioned in their books, which are: vaginal agenesia, intra vaginal tumour, rectovaginal fistula, vesicovaginal fistula, halitosis, bad breath, and metrorrhagia. It is indicated in the medical description, and the possibility and duration of treatment are varied; some of them are easy to cure and do not last long. Some are difficult to cure and may last a long time. Some conditions fall in between these two categories. This should be taken into consideration during the judiciary proceedings; the judge does not independently annulment without medical experience guiding and postpones treatment, if possible, considering the controls decided by the Fuqaha’ to address these demerits.

Malignant neoplasms of the vagina: A 30-year review from the Republic of Belarus

ObjectiveTo perform a retrospective review of patients diagnosed with vaginal malignant neoplasms (VMN) in the Republic of Belarus. MethodsThe Belarusian Cancer Registry was reviewed for patients diagnosed with VMN from 1990 to 2019. The data collected included age at diagnosis, demographic information, histology, stage, treatment modalities, and outcomes. Data were compared across decades (1990–1999, 2000–2009, and 2010–2019). ResultsA total of 868 patients were diagnosed with VMN in Belarus between 1990 and 2019. The estimated age-standardized incidence rate of VMN per 100,000 female population increased from 0.1 in 1999 to 0.4 in 2019 (p < 0.05). The mortality rate for this period was 0.0–0.2 per 100,000 female population. Of all newly diagnosed cases of VMN, 70.9% (n = 615) lived in urban centers and 29.1% (n = 253) lived in rural areas. The most common histological type was squamous cell carcinoma, accounting for 78.4% of cases. The median age at diagnosis was 63.4 years (range, 15.0–87.0 years). When compared across the three decades, the number of stage I cases increased slightly more than twofold (from 19.1% to 38.5% for 1990–1999 to 2010–2019). Furthermore, the number of stage III cases decreased from 30.3% to 13.0% from 1990 to 1999 to 2010–2019. There were no significant changes in the number of patients diagnosed with stage II or IV disease over time. The overall 5-year survival rate for the entire group was 68.7 ± 5.1%, with no statistically significant difference between women living in urban centers vs. rural areas (67.8 ± 5.1% vs. 65.8 ± 10.4%; p = 0.99). However, there was a 26.2% increase in the 5-year survival rate for the entire group over the study period. This increase was higher for women living in rural areas (+61.7%) than for those in urban centers (+51.3%); p > 0.05. Furthermore, a comparison of 5-year adjusted survival rates between 2000 and 2015 showed increased survival for stages I, II, and III, with the most significant increase noted for stage III disease (2.4-fold increase). ConclusionsThis retrospective study found that the survival rates of women with VMN in Belarus have improved over the past 30 years. This is likely due to improvements in early detection as well as improved approaches to treatment, particularly for those living in rural areas. Additional study is needed to further understand and improve the outcomes of women diagnosed with VMN in Belarus.

Comparison of the diagnostic value of [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer: a prospective study.

To compare the diagnostic value of [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer patients. Patients pathologically diagnosed with cervical cancer and with a T stage ≤ T2a2 were prospectively enrolled. All patients underwent whole-body [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT within 2weeks, and surgical treatment was performed within 10days after PET. Twenty-five patients were enrolled. Twenty patients underwent radical hysterectomy, among which all of them underwent pelvic lymphadenectomy, and 10 patients underwent para-aortic lymphadenectomy. Three patients received merely laparoscopic lymphadenectomy without hysterectomy. Two patients with both [18F]FDG and [68Ga]Ga-FAPI-04 lymph node high metabolism were staged as FIGO IIIC1r, and concurrent chemoradiation therapy (CCRT) was performed. [18F]FDG and [68Ga]Ga-FAPI-04 had equivalent detection ability on primary tumors, with a positive detection rate of 96.0%. The accuracy of T staging using [18F]FDG and [68Ga]Ga-FAPI-04 was relatively 50% and 55.0%. Elevated and underrated staging was due to misdiagnosis of either vaginal infiltration or tumor size. In terms of lymph node metastasis detection, the specificity of [68Ga]Ga-FAPI-04 was 100% (95% CI, 84.6% ~ 100.0%), which was significantly higher than [18F]FDG (59.1% (95% CI, 36.4% ~ 79.3%)) (p = 0.004). [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT demonstrated an equivalent detection ability on cervical cancer primary tumors. However, [68Ga]Ga-FAPI-04 PET/MR's diagnostic value in lymph node metastasis was significantly higher than [18F]FDG PET/CT. [68Ga]Ga-FAPI-04 PET/MR has the potential for more accurate treatment planning, thus clarifying fertility preservation indications for early-stage young patients.

Evaluating dose distributions of high dose rate 60Co brachytherapy in an asymmetric tumor: A comparison of different designs of vaginal cylindrical applicators

The aim of this study is to evaluate organ-at-risk (OAR) doses obtained from different designs of intracavitary cylinder applicators during high-dose-rate (HDR) brachytherapy of an asymmetric vaginal tumor. Dose distributions around five cylinder applicators were obtained using the Geant4 toolkit. Three of these applicators are commercially available: single-channel, multi-channel, and shielded. Additionally, two proposed sub-configurations were evaluated: (I) a combination of the multichannel applicator with a central shield and (II) a dynamically modulated cylinder (DMC). The dose distributions of the proposed applicators were compared to those of the single-channel cylinder applicator. The results showed that using a cylindrical applicator with a higher degree of freedom in plan optimization can improve OAR, sparing up to 60% for the rectum and 20% for the bladder. In conclusion, this work suggests using a new design of a cylindrical applicator to enhance the therapeutic ratio of brachytherapy for asymmetric and irregularly shaped vaginal tumors.

Outcome and late effects of patients treated for childhood vaginal malignant germ cell tumors.

Vaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2years old and raise the question of the optimal local treatment. We included children treated for vaginal MGCT according to the French TGM-95/2013 regimen. Patients were classified as standard risk (SR: localized disease and alpha-fetoprotein (AFP)<10,000ng/mL) or high risk (HiR: metastatic and/or AFP>10,000ng/mL) and were treated, respectively, with three to five VBP (vinblastine-bleomycin-cisplatin) or four to six VIP (etoposide-ifosfamide-cisplatin), followed by conservative surgery and/or brachytherapy in case of post-chemotherapy residuum. Fourteen patients were included (median age=12months), of which six (43%) were classified as HiR. AFP levels were normalized after first-line chemotherapy in all cases but one. A vaginal post-chemotherapy residuum (median size=8mm, range: 1-24mm) was observed in 13/14 patients, treated by complete resection in seven of 13 (viable cells in three of seven), incomplete resection in four of 13 (viable cells in two of four), with adjuvant brachytherapy in two of 13, and exclusive brachytherapy in two of 13 (viable cells in one of six). Among the six patients with viable disease, four patients received adjuvant chemotherapy. One patient (SR) experienced immediate postoperative relapse despite presenting no viable residual cells and was treated with four VIP cycles and brachytherapy. At last follow-up (median=4.6years, range: 0.5-16), all patients were alive in complete remission. Five patients suffered from vaginal sequelae with synechiae and/or stenosis (of whom four had undergone brachytherapy). Childhood vaginal MGCTs show a highly favorable prognosis with risk-adapted chemotherapy and local treatment of post-chemotherapy residuum (preferably by conservative surgery with partial vaginectomy). Brachytherapy could be an alternative when conservative surgery is not deemed possible or in cases of incomplete resection with residual viable cells.

Defining the Transcriptional Landscapes of the Tumor Microenvironment of Cervical and Vaginal Cancers at Single-Cell Resolution

Malignancies found within vaginal tissue are often diagnosed as cancers of the cervix, vulva, or urethra and are clinically treated with similar modalities. However, the rarity of vaginal cancer may be an artifice of categorization; current treatment paradigms do not take into account tissue-specific mutations and differences in mechanistic pathways intracellularly. Understanding the shared and distinctly different transcriptional profiles of vaginal and cervical tumors at a single-cell resolution will provide insights in vaginal tumor biology and will open avenues for future clinical interventions. Biopsies of tumor and adjacent normal tissue from 9 patients (3 adenocarcinomas (ADC), 3 squamous cell carcinomas (SCC) from the cervix, and 3 vaginal SCC) were collected and analyzed by single-cell RNA sequencing (scRNA-seq) to compare the tumor, immune, and stromal features of cervical and vaginal cancers. Collectively, over 50,000 cells were analyzed by scRNA-seq in this study. We performed dimensionality reduction and clustering analysis of the single-cell transcriptomes to identify the major cell types composing the vaginal and cervical tumor tissues. Compared to Cervical SCC, Vaginal SCC tissues showed reduced fractions of macrophages (-2.7 log2-fold; padj < 0.02) and T cells (-3.7 log2-fold; padj < 0.02) by differential cell proportion analysis (RAISIN). Likewise, the vaginal SCC epithelial cell compartments showed downregulation of inflammatory pathways including TNF signaling via NFKB (NES = -5.7, padj = 5.0 × 10-19), IL2 STAT5 signaling (NES = -4.5, padj = 1.6 × 10-12), and interferon gamma response (NES = -4.3, padj = 9.4 × 10-12), among the Hallmark pathway collection. On the other hand, vaginal SCC epithelial cells showed significant upregulation of oxidative phosphorylation (NES = 4.8, padj = 1.7 × 10-17), p53 pathway (NES = 4.2, padj = 1.8 × 10-13), mTORC1 signaling (NES = 4.2, padj = 1.9 × 10-13), and estrogen early and late response (NES = 4.0, padj < 7.5 × 10-12) compared to cervical SCC. These results highlight distinct differences in the cell type composition and cancer epithelial pathways in vaginal vs. cervical SCC. Among upregulated pathways in vaginal SCC, ER and mTORC1 pathway activation may represent targets for therapeutic intervention worthy of further investigation.

A phase I study of the Wee1 kinase inhibitor adavosertib (AZD1775) in combination with chemoradiation in cervical, upper vaginal, and uterine cancers

ObjectiveWee1 kinase is a crucial regulator of the G2/M checkpoint which prevents entry of damaged DNA into mitosis. Adavosertib (AZD1775), a selective inhibitor of Wee1, induces G2 escape and increases...

ESTRO/ESGO/SIOPe Guidelines for the management of patients with vaginal cancer

Primary vaginal malignancies are rare, comprising only 2% of all female genital tract malignancies in adults and 4.5% in children. As part of its mission to improve the quality of...