RARE DISEASE
Vaginal carcinoma
Vaginal carcinoma
Vaginal carcinoma
Synonyms: Vaginal malignant epithelial tumor
Synonyms: Vaginal malignant epithelial tumor
Synonyms: Vaginal malignant epithelial tumor
Drug discovery
0
drugs
With orphan designations
Overview
Vaginal carcinoma is a rare gynecologic malignancy, representing 1-2% of female genital tract cancers. Most cases are squamous cell carcinomas linked to HPV, while adenocarcinomas and sarcomas are less common. Presenting symptoms include abnormal bleeding, discharge, or pelvic pain. Diagnosis involves biopsy and imaging (MRI/CT) for staging. Treatment depends on stage and location, combining radiotherapy (primary modality), surgery (early-stage lesions), and chemotherapy. Prognosis correlates with stage, with 5-year survival exceeding 70% for localized disease but declining sharply with advanced/metastatic spread [1][2][5][16].
Burden
Global annual incidence: ~17,500 cases (0.7/100,000), with 5-year survival <50% for regional disease [9][14][19].
Disparities: Black women face 72% higher mortality vs. white women due to late-stage diagnoses [7][9][12].
Treatment toxicity: 30-40% risk of vaginal stenosis, fistula, or sexual dysfunction post-radiation [3][6][13].
Therapies
Radiation: Primary treatment (brachytherapy ± external beam), achieving 80-90% control for stage I [3][6][8].
Surgery: Reserved for small, localized tumors (vaginectomy) or salvage post-radiation [6][13][18].
Chemoradiation: Cisplatin-based regimens for advanced stages or nodal involvement [3][6][8].
Categories: rare gynecological and obstetric diseases, rare neoplastic diseases
Research Papers
470 drug discovery papers about Vaginal carcinoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
470 drug discovery papers about Vaginal carcinoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-05-08 | Genomic Profiling of Primary Vaginal Tumors: Molecular Landscape, Clinical Significance, and Future Directions
Squamous cell carcinoma (SCC) is the most common histological subtype of primary vaginal cancer, a rare gynaecologic disease that accounts for fewer than 2% of female genital tract cancers. Because it is uncommon, therapeutic approaches are frequently generalised from vulvar and cervical malignancies, which restricts individualised treatment plans. Recent advancements in multi-omics and next-generation sequencing (NGS) technologies have made it possible to profile the genomes of primary vaginal tumours, revealing their molecular heterogeneity and finding useful mutations. The genomic landscape of primary vaginal tumours is reviewed in this study, with an emphasis on important genetic changes, molecular markers linked to HPV, and clinically significant pathways. To find recurring mutations, copy number variations, and pathway-level disruptions, a methodical research approach was used by analysing recent genomic publications, cancer genome archives, and clinical sequencing reports. To show the frequency of mutations like TP53, PIK3CA, PTEN, CDKN2A, KRAS, and changes in EGFR and TERT, data were collated. Different molecular characteristics, such as viral-driven oncogenesis vs genomic instability and p53 disruption, are revealed by comparing the profiles of HPV-positive and HPV-negative tumours. Prognostic stratification, immunotherapy biomarkers, and targeted therapeutics are all considered in regard to the clinical consequences of genetic profiling.Challenges such as small cohort sizes, tumor heterogeneity, and limited clinical trial evidence remain barriers to translation. Future perspectives emphasize integrated transcriptomics, liquid biopsy monitoring, and AI-driven precision oncology. Genomic profiling offers a transformative approach for improving diagnosis, prognostic prediction, and biomarker-guided therapy in vaginal cancer.
2026-01-30 | Efficacy and safety of photodynamic therapy for vaginal intraepithelial neoplasia: A systematic review and meta-analysis.
Vaginal Intraepithelial Neoplasia (VaIN) is a precancerous condition that can progress to vaginal cancer if untreated. Photodynamic Therapy (PDT), recognized for its minimally invasive nature and favorable side effect profile, is increasingly employed for VaIN treatment; however, comprehensive evidence synthesis on its efficacy and safety remains limited. This study aims to comprehensively evaluate the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in treating VaIN. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases for studies evaluating PDT efficacy in VaIN. Primary outcomes were complete response (CR) rate and HPV clearance rate; secondary outcomes included recurrence rate and adverse events (AE). Meta-analysis was performed using Stata 18.0. Nine trials (421 patients) were included. Pooled outcomes: 6-month CR:87% (95% CI: 78%-94%), 12-month CR:84% (95% CI:76%-91%); 6-month HPV clearance:61% (95% CI:55%-66%), 12-month:73% (95% CI:67%-78%); 6-month HPV16/18 clearance:71% (95% CI:61%-80%), 12-month:76% (95% CI:63%-88%); 6-month recurrence:4% (95% CI:2%-8%), 12-month:7% (95% CI:0%-24%); AEs: Increased vaginal discharge (20%, 95% CI: 8%-36%), itching (25%, 95% CI: 1%-62%), burning sensation (23%, 95% CI: 1%-57%), abdominal pain (7%, 95% CI: 0%-21%), and mild vaginal bleeding (0%, 95% CI: 0%-3%). No serious AEs. ALA-PDT demonstrates high efficacy and favorable safety in treating VaIN. However, as current evidence primarily stems from single-arm studies, future high-quality multicenter randomized controlled trials are essential to confirm these findings and directly compare ALA-PDT with standard therapies.
2025-12-31 | Clear Cell Carcinoma of the Vagina in an 11-Year-Old Girl: A Case Report on Clinical, Imaging, and Immunophenotypic Features.
Vaginal clear cell carcinoma (CCC) is a rare malignant tumor in the pediatric population and may occur even in the absence of in utero exposure to diethylstilbestrol (DES). We report the case of an 11-year-old girl without DES exposure who presented with persistent foul-smelling vaginal discharge, abdominal pain, and weight loss. Imaging revealed a large vaginal mass with regional lymph node involvement. Histopathology confirmed CCC with Müllerian immunophenotype. The disease was classified as advanced and unresectable, and the patient was treated with concurrent cisplatin-based chemoradiation followed by high-dose-rate interstitial brachytherapy. She achieved significant tumor reduction and remains clinically disease-free to date. This case underscores the diagnostic complexity of pediatric vaginal CCC and supports chemoradiation with brachytherapy as an effective strategy for unresectable disease.
2025-11-30 | Association of Cigarette Smoking and Vaginal Cancer Risk: A Comprehensive Systematic Review and Quantitative Synthesis of Epidemiological Evidence
Introduction Primary invasive vaginal cancer (VC) is a rare malignancy, predominantly presenting as vaginal squamous cell carcinoma (VSCC) (Cancer Center). While persistent infection with high-risk human papillomavirus (HPV) is the principal etiological agent, cigarette smoking is a recognized and critical co-factor that promotes pathogenesis (Brinton et al., 1986; Cancer Center). Dedicated systematic reviews quantifying the association between active smoking and VC, particularly focusing on the crucial interaction with HPV status, are necessary to refine preventative strategies. Methods A systematic search, adhering to PRISMA guidelines for observational studies (PRISMA), was performed across major medical databases to identify case-control and prospective cohort studies investigating the risk of invasive VC or high-grade vaginal intraepithelial neoplasia (VAIN 2/3) associated with active cigarette smoking. Methodological quality and risk of bias were rigorously assessed using the Newcastle-Ottawa Scale (NOS), which is appropriate for non-randomized designs (Newcastle-Ottawa Scale). The analysis integrated adjusted Odds Ratios (ORs) and Relative Risks (RRs) from 15 included studies, prioritizing those that controlled for HPV status and age (Madsen et al., 2012). Ten specific quantitative and qualitative outcome metrics were analyzed, focusing on dose-response, reversibility, and histological specificity. Results The synthesis of 15 observational studies established a strong association between current smoking and increased risk of invasive VC (Pooled OR: 2.10; 95% CI 1.70–2.60). Stratified analysis from the highest-quality studies demonstrated profound effect modification: the elevated risk was restricted entirely to HPV-positive VSCC cases (Adjusted OR: 2.79; 95% CI 1.30–5.99), with negligible risk observed among HPV-negative VSCC cases (Adjusted OR: 1.03; 95% CI 0.36–2.94) (Madsen et al., 2012). A compelling dose-response relationship was confirmed, with heavy smokers experiencing the highest risk elevation (Pooled OR: 2.45) (Brinton et al., 1986). Biological plausibility is supported by the direct detection of the potent tobacco-specific carcinogen, NNK, in the cervical and vaginal fluid of smokers (Hecht et al., 1999). Notably, former smokers showed a substantially attenuated risk (Pooled OR: 1.25), confirming the reversibility of the promotional effect upon cessation (Brinton et al., 1986). Discussion The epidemiological evidence confirms cigarette smoking as a critical, non-initiating co-factor in VSCC pathogenesis. Smoking operates via direct localized delivery of carcinogens (Hecht et al., 1999) and systemic immunosuppression, impairing the host's ability to clear persistent high-risk HPV infection (Daling et al., 1994; Smith et al., 1999). This co-factor role explains the observed dependency on HPV status and the specificity for squamous cell carcinoma (Madsen et al., 2012). Clinical data supports that smoking cessation post-diagnosis significantly improves survival outcomes and treatment efficacy (Cinciripini et al., 2024; Westmaas et al., 2015). Conclusion Cigarette smoking is an established, major modifiable risk factor for vaginal squamous cell carcinoma, acting synergistically with Human Papillomavirus infection. Public health interventions must integrate aggressive smoking cessation programs into prevention and treatment strategies for HPV-related anogenital malignancies to maximize disease control and survival benefits.
2025-11-23 | Effect of vaginal microbial infections on the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy for vaginal intraepithelial neoplasia.
Vaginal intraepithelial neoplasia (VAIN) is a precancerous condition with significant potential for malignant transformation. The 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is considered as a novel approach to treat VAIN. Recent studies have shown that an imbalance in the vaginal microbiota can affect the progression of VAIN. Thus, the effect of imbalanced microbiota on the efficacy of ALA-PDT for treating VAIN needs to be determined. Sixty-five female patients diagnosed with VAIN were recruited. 5-aminolevulinic acid was applied topically to the vaginal wall, followed by 635 nm red light at intervals of 7-14 days. Cytological inspections, high risk human papillomavirus (HR-HPV) genotyping, vaginal colposcopy examinations, histopathology and culture and identification of vaginal microflora were performed before and after treatment. Among the 62 patients, the complete remission rate (CRR) of vaginal wall lesions was 85.5 %, and the HR-HPV clearance rate was 61.3 %. In the balanced vaginal microbiota group, the CRR of vaginal wall lesions reached 97.2 %, with an HR-HPV clearance rate of 75.1 %. In the imbalanced vaginal microbiota group, the CRR of vaginal wall lesions was only 65.5 %, with an HR-HPV clearance rate of 48.3 %. There was a trend of improved clearance of lesions and HR-HPV when the vaginal microbiota was balanced (p= 0.002 and p= 0.038, respectively). During the process of clinical treatment and the 1-year follow-up period, all patients experienced minimal adverse reactions. The findings of this study demonstrate that ALA-PDT is a clinically effective and safe treatment for VAIN, and the vaginal microbiota's status is a key factor affecting the efficacy of ALA-PDT for VAIN.
vaccines
2026-07-06 | Human Papillomavirus Infection in Patients With VaIN and Vaginal Cancer: A Retrospective Cross-Sectional Study.
Vaginal cancer is a rare malignancy, and the research on it is not comprehensive yet. To explore the characteristics of human papillomavirus (HPV) infection in patients with vaginal intraepithelial neoplasia (VaIN) and vaginal cancer. This study included patients who underwent colposcopy and biopsy of suspected sites at the Second Hospital of Shanxi Medical University from January 2014 to December 2023 due to abnormal cytology results and/or positive HPV test. Those diagnosed with benign inflammatory reaction of the vagina (ie, vaginitis), VaIN and vaginal cancer according to histologic results were selected as the study objects. Clinical data such as age, menopause, clinical manifestations and previous screening history were collected. We aimed to analyze the distribution and characteristics of HPV in VaIN and vaginal cancer patients. A total of 5,180 patients were included in this study. Of the total, 2,739 patients had VaIN1, 641 had VaIN2/3, and 251 had vaginal cancer. There were 235 patients with vaginal squamous cell carcinoma (VaSCC) and 16 patients with vaginal adenocarcinoma. A total of 4,548 patients were infected with HPV. The HPV positive rate was 95.5% in VaIN2/3, 86.0% in VaSCC and 43.8% in adenocarcinoma of the vagina. The most common 5 HPV types were HPV16, 52, 58, 53, and 18. The positive rate of HPV18 in the adenocarcinoma of the vagina was the highest. HPV16, 52, 58, 53, and 18 are the predominant genotypes in VaIN and vaginal cancer in Shanxi, China. HPV testing provides additional benefits for the detection of vaginal lesions during cervical cancer screening. Active HPV vaccination may help reduce the burden of these lesions.
2022-09-23 | Vaccination with human alphapapillomavirus-derived L2 multimer protects against human betapapillomavirus challenge, including in epidermodysplasia verruciformis model mice.
Human alphapapillomaviruses (αHPV) infect genital mucosa, and a high-risk subset is a necessary cause of cervical cancer. Licensed L1 virus-like particle (VLP) vaccines offer immunity against the nine most common αHPV associated with cervical cancer and genital warts. However, vaccination with an αHPV L2-based multimer vaccine, α11-88x5, protected mice and rabbits from vaginal and skin challenge with diverse αHPV types. While generally clinically inapparent, human betapapillomaviruses (βHPV) are possibly associated with cutaneous squamous cell carcinoma (CSCC) in epidermodysplasia verruciformis (EV) and immunocompromised patients. Here we show that α11-88x5 vaccination protected wild type and EV model mice against HPV5 challenge. Passive transfer of antiserum conferred protection independently of Fc receptors (FcR) or Gr-1+ phagocytes. Antisera demonstrated robust antibody titers against ten βHPV by L1/L2 VLP ELISA and neutralized and protected against challenge by 3 additional βHPV (HPV49/76/96). Thus, unlike the licensed vaccines, α11-88x5 vaccination elicits broad immunity against αHPV and βHPV.
2018-09-24 | Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial.
Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543. Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0-99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related. The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide. Merck & Co, Inc.
2016-07-27 | 9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV.
Human papillomavirus (HPV) is the causative agent of nearly all cervical cancer cases as well as a substantial proportion of anal, vulvar, vaginal, penile and oropharyngeal cancers, making it responsible for approximately 5% of the global cancer burden. The first-generation HPV vaccines that is, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine were licensed in 2006 and 2007, respectively. A second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage was initiated even before the first vaccines were approved. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70 to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85-95% of HPV-related vulvar, vaginal and anal cancers. Overall, the 9vHPV vaccine addresses a significant unmet medical need, although further health economics and implementation research is needed.
2015-06-05 | Human papillomavirus burden in different cancers in Iran: a systematic assessment.
Certain types of human papillomaviruses (HPVs) are undoubtedly involved in genesis of human malignancies. HPV plays an etiological role in cervical cancer, but also in many vaginal, vulvar, anal and penile cancers, as well as head and neck cancers. In addition, a number of non-malignant diseases such as genital warts and recurrent respiratory papillomatosis are attributable to HPV. Moreover, HPV forms have detected in several other cancers including esophageal squamous cell carcinoma, lung, prostate, ovarian, breast, skin, colorectal and urinary tract cancers, but associations with etiology in these cases is controversial. The aim of this systematic assessment was to estimate the prevalence of HPV infection and HPV types in HPV-associated cancers, HPV-related non-malignant diseases and in cancers that may be associated with HPV in Iran. The present investigation covered 61 studies on a variety of cancers in Iranian populations. HPV prevalence was 77.5 % and 32.4% in cervical cancer and head and neck cancers, respectively. HPV was detected in 23.1%, 22.2%, 10.4%, 30.9%, 14% and 25.2% of esophageal squamous cell, lung, prostate, urinary tract cancers, breast and skin cancers, respectively. HPV16 and 18 were the most frequent HPV types in all cancers. The findings of present study imply that current HPV vaccines for cervical cancer may decrease the burden of other cancers if they are really related to HPV.
antibodies
2026-05-28 | Beyond extrapolation: Immunotherapy outcomes in recurrent vulvovaginal carcinoma.
To evaluate the efficacy, survival outcomes, and toxicity of immune checkpoint inhibitors (ICI) in patients with recurrent vulvar and vaginal carcinomas (VVC). This retrospective cohort study included patients with recurrent VVC treated with ICI at a single tertiary care center between August 2016 and September 2025. Treatment response was assessed using RECIST 1.1 criteria. Objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were evaluated. Survival outcomes were estimated using the Kaplan-Meier method. Twenty-one patients with recurrent VVC received ICI therapy, with a median age of 73.0 years (IQR, 62.4-77.9); 17 were evaluable for response. PD-L1 expression was positive (CPS ≥1) in 85.7% (n = 18). Pembrolizumab was the most administered ICI (76.2%, 16/21), and most patients received ICI monotherapy (66.7%, 14/21). The median number of ICI cycles was 4 (IQR, 2-6). The ORR was 29.4% (n = 5) with a median DOR of 14.0 months (IQR, 4.97-16.0). Median PFS was 3.0 months (95% CI 1.9-3.4) and median OS was 4.6 months (95% CI 3.7-8.5). Median PFS was 3.1 months for patients receiving combination therapy and 2.5 months for those receiving monotherapy (p = 0.50). Immune-related adverse events occurred in 38.1% (n = 8), including grade ≥ 3 events in 19.0% (n = 4). Disease progression was the most common reason for treatment discontinuation (57.1%, n = 12). ICI demonstrated modest activity in recurrent VVC, with durable responses observed in a small subset of patients. Although survival outcomes were limited overall, ICI therapy may provide meaningful benefit for select patients.
2026-01-20 | A Labial Mass Demonstrated With Sonography and MRI Diagnostic Correlation
Vaginal and labial masses are uncommon and can have a wide range of differentials, both benign and malignant. Included in these masses are hemangiomas, papillomas, mucosal polyps, leiomyomas, and carcinomas. A case report is presented of a patient with a history of surgically treated squamous cell carcinoma, of the vaginal wall, who returned years later with a new palpable labial mass. The initial sonogram pertaining to the new palpable lump showed what was believed may be an irregular, hypoechoic structure, with internal vascularity. A second sonogram conducted several weeks later, in the same region, revealed different findings. The same area imaged several weeks earlier, reevaluated with sonography, demonstrated an ovoid-shaped complex fluid collection with an irregular margin. It contained multiple lacy septa and reflections, without evidence of internal arterial or venous flow. The mass was suspected to be a probable hematoma; however, a magnetic resonance imaging examination was conducted a few days later and the results characterized the mass as a seroma.
2026-01-01 | Feasibility study of photoimmunotherapy combination with ASP-1929 for vulvar, vaginal, and cervical cancer
OBJECTIVE: The aim of this study was to evaluate the feasibility of photoimmunotherapy (PIT) using ASP-1929, an anti-epidermal growth factor receptor (EGFR) antibody-dye conjugate, for vulvar, vaginal, and cervical cancers by validating EGFR expression and establishing immunohistochemistry (IHC)-based eligibility criteria for a phase II trial, HICARi study. METHODS: Cetuximab-binding activity was analyzed in gynecologic cancer cell lines (CaSki, HeLa, and Ishikawa) using flow cytometry and compared with positive controls (A431 and BxPC-3) and a low-EGFR control (MCF-7). IHC was performed on cell blocks and clinical specimens of vulvar, vaginal, and cervical cancers (validation cohort, n=27; screening cohort, n=40). RESULTS: CaSki demonstrated comparable or higher EGFR binding than BxPC-3, whereas HeLa and Ishikawa showed weaker binding. IHC staining intensity correlated with flow cytometry findings. Squamous cell carcinomas consistently exhibited moderate-to-strong EGFR expression, whereas non-squamous carcinomas displayed variable expression. EGFR positivity was defined as >30% of tumor cells with at least moderate membranous staining (2+ or 3+). In the validation cohort, EGFR positivity was observed in 71.4% of the vulvar, 80.0% of the vaginal, and 87.5% of the cervical cancers. The screening cohort showed similar rates: 88.9% of vulvar, 100% of vaginal, and 75.0% of cervical cancers. CONCLUSION: We demonstrated correlation between cetuximab-binding and IHC staining intensity, establishing IHC criteria (≥2+) for patient selection. EGFR positivity (71.4%-87.5%) indicates substantial eligibility for ASP-1929 PIT. Therapeutic efficacy will be evaluated in the HICARi study.
2025-05-28 | Phase 2 dose expansion of START-001: A phase 1/2 study of invikafusp alfa (STAR0602), a first-in-class, selective T cell receptor (TCR)-targeting, bifunctional antibody-fusion molecule, as monotherapy in patients with antigen-rich tumors resistant to anti-PD(L)-1.
TPS2687 Background: Many patients do not respond to anti-PD(L)-1-based therapies and most responders eventually develop resistance. Thus, the development of effective therapies for anti-PD(L)-1 resistance is a significant unmet medical need. Invikafusp, a selective, dual T cell agonist targeting Vβ6/Vβ10 T cells, is being evaluated in START-001: a multicenter Phase 1/2 monotherapy trial in patients with anti-PD(L)1-resistant, antigen-rich (TMB-H, MSI-H/dMMR, or virally associated) solid tumors. The completed Phase 1 dose escalation of intravenous invikafusp, Q2W, per 3+3 design, identified a recommended Phase 2 dose (RP2D) of 0.08 mg/kg, and demonstrated clinically meaningful single-agent anti-tumor activity in patients with anti-PD(L)-1 resistant tumors, including confirmed partial responses in TMB-H, microsatellite stable, colorectal cancer (CRC) patients with one durable response lasting ~12 months. It promoted potent and selective expansion of mainly CD8+ Vβ6/ Vβ10 T cells with a novel central memory T cell phenotype, and led to ctDNA decrease and expansion of antigen-specific T cells. Based on these results, the US FDA granted Fast Track Designation for invikafusp in TMB-H CRC. Methods: Study design: Using an optimal Simon’s 2 stage design, Phase 2 of START-001 is a dose expansion at the RP2D, to further investigate the safety and anti-tumor activity of invikafusp in 9 cohorts of patients who have the following solid tumors: 1) tissue-agnostic, TMB-H; 2) tissue-agnostic, dMMR/MSI-H; 3) CRC (both Ras wild-type and mutant) TMB-H and/or MSI-H/dMMR); 4) virally associated tumors such as Merkel cell carcinoma, cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers, or EBV-related solid tumors; 5) metastatic triple-negative breast cancer; 6) platinum-resistant epithelial ovarian cancer; 7) metastatic castration-resistant prostate cancer; 8) primary stage IV or recurrent non-small cell lung cancer; and 9) immunogenic tumors (e.g., cSCC, melanoma and RCC). Major Eligibility criteria: ≤ 3 lines of prior cancer therapies [anti-PD(L)-1s allowed] for advanced or metastatic disease; intolerance to standard therapies including anti-PD(L)-1s allowed; no liver metastases or adequately treated liver metastases either locally (e.g., by surgery, radiofrequency ablation, or chemoembolization) or systemically and stable for 3 months. Primary objective: to further evaluate anti-tumor activity of invikafusp as monotherapy in each of the above-described 9 cohorts of patients with anti-PD(L)-1-resistant, unresectable, locally advanced, or metastatic solid tumors. Primary endpoint: overall response rate (ORR) per iRECIST. The enrollment to the first three cohorts has begun. Clinical trial information: NCT05592626 .
2025-04-26 | Advances and Challenges in the Treatment of HPV-Associated Lower Genital Tract Cancers by Immune Checkpoint Blockers: Insights from Basic and Clinical Science.
Human papillomavirus (HPV)-related lower genital cancers, including cervical cancer, anal squamous cell carcinoma (SCC), vaginal cancer, vulvar cancer, and penile cancer, pose a significant health burden, with approximately 45,000 new cases diagnosed annually. Current effective treatment modalities include chemoradiotherapy, systemic chemotherapy, and immune checkpoint inhibitors (ICIs). The tumor microenvironment in HPV-related cancers is characterized by immune evasion mechanisms, including the modulation of immune checkpoints such as PD-L1/PD-1. HPV oncoproteins E5, E6, and E7 play crucial roles in this process, altering the expression of immune inhibitory molecules and the recruitment of immune cells. ICIs, such as programmed cell death protein 1 (PD-1) inhibitors, have shown efficacy in enhancing the immune response against HPV-associated tumors by blocking proteins that allow cancer cells to evade immune surveillance. Recent studies have demonstrated that HPV-positive tumors exhibit a more favorable response to ICI-based therapies compared to HPV-negative tumors. The integration of ICIs into treatment regimens for HPV-related cancers has been supported by several clinical trials. The inclusion of ICIs in the treatment approach for HPV-related lower genital cancers presents a promising opportunity for improving patient outcomes. Ongoing research and clinical trials are advancing our understanding of the immune microenvironment and the therapeutic potential of immunotherapy for these cancers.
oligonucleotides
2025-07-28 | DNA methylation testing for vulvar cancer risk stratification in patients with high-grade vulvar intraepithelial neoplasia: a population-based cohort study.
High-grade vulvar intraepithelial neoplasia (VIN) is the precursor of vulvar cancer. The main variants are human papillomavirus (HPV)-associated high-grade squamous intraepithelial lesion (HSIL) and HPV-independent VIN, often clinically referred to as differentiated VIN (dVIN) and associated with vulvar dermatoses, usually lichen sclerosus. Surgical treatment of high-grade VIN often leads to genital deformity, impaired sexual function and reduced quality of life. To optimize clinical management, accurate biomarkers providing information on the cancer risk of high-grade VIN are needed. To investigate the prognostic value of a three-gene methylation marker panel and other potential risk factors for the risk of progression to cancer in patients with HSIL and dVIN. From a population-based cohort of patients diagnosed with high-grade VIN, patients with a histopathologically confirmed diagnosis of HSIL (n = 578) and dVIN (n = 46) were selected. All lesions were tested by a three-gene methylation panel including the genes ZNF582, SST and miR124-2. The vulvar cancer risk and the prognostic value of methylation status, age, HPV genotype, wild-type vs. mutant p53 immunohistochemistry status and presence of lichen sclerosus were estimated by Kaplan-Meier and Cox regression, respectively. Vulvar cancer developed in 26 of 578 patients with HSIL (4.5%) and in 21 of 46 with dVIN (46%) within 5 years. In HSIL, positive methylation status was identified as the only prognostic factor for vulvar cancer development [hazard ratio (HR) 4.87, 95% confidence interval (CI) 1.20-21.45]. The prognostic value of methylation remained present when selecting patients who did not receive radical surgical excision as their primary treatment. In this group, the 5-year cancer risk was 7.7% in methylation-positive HSIL and 1.4% in methylation-negative HSIL (P = 0.008). In dVIN, mutant p53 status was the sole prognostic risk factor for progression to cancer (HR 7.67, 95% CI 1.78-33.08). Despite wide CIs, the three-gene methylation test serves as a promising prognostic tool for cancer risk stratification in patients with vulvar HSIL. Patients with methylation-negative HSIL carry a low cancer risk, allowing for more conservative management strategies. This approach may help avoid overtreatment, reducing morbidity and improving quality of life.
2021-11-23 | Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma
Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.
small molecules
2026-05-08 | Genomic Profiling of Primary Vaginal Tumors: Molecular Landscape, Clinical Significance, and Future Directions
Squamous cell carcinoma (SCC) is the most common histological subtype of primary vaginal cancer, a rare gynaecologic disease that accounts for fewer than 2% of female genital tract cancers. Because it is uncommon, therapeutic approaches are frequently generalised from vulvar and cervical malignancies, which restricts individualised treatment plans. Recent advancements in multi-omics and next-generation sequencing (NGS) technologies have made it possible to profile the genomes of primary vaginal tumours, revealing their molecular heterogeneity and finding useful mutations. The genomic landscape of primary vaginal tumours is reviewed in this study, with an emphasis on important genetic changes, molecular markers linked to HPV, and clinically significant pathways. To find recurring mutations, copy number variations, and pathway-level disruptions, a methodical research approach was used by analysing recent genomic publications, cancer genome archives, and clinical sequencing reports. To show the frequency of mutations like TP53, PIK3CA, PTEN, CDKN2A, KRAS, and changes in EGFR and TERT, data were collated. Different molecular characteristics, such as viral-driven oncogenesis vs genomic instability and p53 disruption, are revealed by comparing the profiles of HPV-positive and HPV-negative tumours. Prognostic stratification, immunotherapy biomarkers, and targeted therapeutics are all considered in regard to the clinical consequences of genetic profiling.Challenges such as small cohort sizes, tumor heterogeneity, and limited clinical trial evidence remain barriers to translation. Future perspectives emphasize integrated transcriptomics, liquid biopsy monitoring, and AI-driven precision oncology. Genomic profiling offers a transformative approach for improving diagnosis, prognostic prediction, and biomarker-guided therapy in vaginal cancer.
2026-01-30 | Efficacy and safety of photodynamic therapy for vaginal intraepithelial neoplasia: A systematic review and meta-analysis.
Vaginal Intraepithelial Neoplasia (VaIN) is a precancerous condition that can progress to vaginal cancer if untreated. Photodynamic Therapy (PDT), recognized for its minimally invasive nature and favorable side effect profile, is increasingly employed for VaIN treatment; however, comprehensive evidence synthesis on its efficacy and safety remains limited. This study aims to comprehensively evaluate the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in treating VaIN. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases for studies evaluating PDT efficacy in VaIN. Primary outcomes were complete response (CR) rate and HPV clearance rate; secondary outcomes included recurrence rate and adverse events (AE). Meta-analysis was performed using Stata 18.0. Nine trials (421 patients) were included. Pooled outcomes: 6-month CR:87% (95% CI: 78%-94%), 12-month CR:84% (95% CI:76%-91%); 6-month HPV clearance:61% (95% CI:55%-66%), 12-month:73% (95% CI:67%-78%); 6-month HPV16/18 clearance:71% (95% CI:61%-80%), 12-month:76% (95% CI:63%-88%); 6-month recurrence:4% (95% CI:2%-8%), 12-month:7% (95% CI:0%-24%); AEs: Increased vaginal discharge (20%, 95% CI: 8%-36%), itching (25%, 95% CI: 1%-62%), burning sensation (23%, 95% CI: 1%-57%), abdominal pain (7%, 95% CI: 0%-21%), and mild vaginal bleeding (0%, 95% CI: 0%-3%). No serious AEs. ALA-PDT demonstrates high efficacy and favorable safety in treating VaIN. However, as current evidence primarily stems from single-arm studies, future high-quality multicenter randomized controlled trials are essential to confirm these findings and directly compare ALA-PDT with standard therapies.
2025-12-31 | Clear Cell Carcinoma of the Vagina in an 11-Year-Old Girl: A Case Report on Clinical, Imaging, and Immunophenotypic Features.
Vaginal clear cell carcinoma (CCC) is a rare malignant tumor in the pediatric population and may occur even in the absence of in utero exposure to diethylstilbestrol (DES). We report the case of an 11-year-old girl without DES exposure who presented with persistent foul-smelling vaginal discharge, abdominal pain, and weight loss. Imaging revealed a large vaginal mass with regional lymph node involvement. Histopathology confirmed CCC with Müllerian immunophenotype. The disease was classified as advanced and unresectable, and the patient was treated with concurrent cisplatin-based chemoradiation followed by high-dose-rate interstitial brachytherapy. She achieved significant tumor reduction and remains clinically disease-free to date. This case underscores the diagnostic complexity of pediatric vaginal CCC and supports chemoradiation with brachytherapy as an effective strategy for unresectable disease.
2025-11-30 | Association of Cigarette Smoking and Vaginal Cancer Risk: A Comprehensive Systematic Review and Quantitative Synthesis of Epidemiological Evidence
Introduction Primary invasive vaginal cancer (VC) is a rare malignancy, predominantly presenting as vaginal squamous cell carcinoma (VSCC) (Cancer Center). While persistent infection with high-risk human papillomavirus (HPV) is the principal etiological agent, cigarette smoking is a recognized and critical co-factor that promotes pathogenesis (Brinton et al., 1986; Cancer Center). Dedicated systematic reviews quantifying the association between active smoking and VC, particularly focusing on the crucial interaction with HPV status, are necessary to refine preventative strategies. Methods A systematic search, adhering to PRISMA guidelines for observational studies (PRISMA), was performed across major medical databases to identify case-control and prospective cohort studies investigating the risk of invasive VC or high-grade vaginal intraepithelial neoplasia (VAIN 2/3) associated with active cigarette smoking. Methodological quality and risk of bias were rigorously assessed using the Newcastle-Ottawa Scale (NOS), which is appropriate for non-randomized designs (Newcastle-Ottawa Scale). The analysis integrated adjusted Odds Ratios (ORs) and Relative Risks (RRs) from 15 included studies, prioritizing those that controlled for HPV status and age (Madsen et al., 2012). Ten specific quantitative and qualitative outcome metrics were analyzed, focusing on dose-response, reversibility, and histological specificity. Results The synthesis of 15 observational studies established a strong association between current smoking and increased risk of invasive VC (Pooled OR: 2.10; 95% CI 1.70–2.60). Stratified analysis from the highest-quality studies demonstrated profound effect modification: the elevated risk was restricted entirely to HPV-positive VSCC cases (Adjusted OR: 2.79; 95% CI 1.30–5.99), with negligible risk observed among HPV-negative VSCC cases (Adjusted OR: 1.03; 95% CI 0.36–2.94) (Madsen et al., 2012). A compelling dose-response relationship was confirmed, with heavy smokers experiencing the highest risk elevation (Pooled OR: 2.45) (Brinton et al., 1986). Biological plausibility is supported by the direct detection of the potent tobacco-specific carcinogen, NNK, in the cervical and vaginal fluid of smokers (Hecht et al., 1999). Notably, former smokers showed a substantially attenuated risk (Pooled OR: 1.25), confirming the reversibility of the promotional effect upon cessation (Brinton et al., 1986). Discussion The epidemiological evidence confirms cigarette smoking as a critical, non-initiating co-factor in VSCC pathogenesis. Smoking operates via direct localized delivery of carcinogens (Hecht et al., 1999) and systemic immunosuppression, impairing the host's ability to clear persistent high-risk HPV infection (Daling et al., 1994; Smith et al., 1999). This co-factor role explains the observed dependency on HPV status and the specificity for squamous cell carcinoma (Madsen et al., 2012). Clinical data supports that smoking cessation post-diagnosis significantly improves survival outcomes and treatment efficacy (Cinciripini et al., 2024; Westmaas et al., 2015). Conclusion Cigarette smoking is an established, major modifiable risk factor for vaginal squamous cell carcinoma, acting synergistically with Human Papillomavirus infection. Public health interventions must integrate aggressive smoking cessation programs into prevention and treatment strategies for HPV-related anogenital malignancies to maximize disease control and survival benefits.
2025-11-23 | Effect of vaginal microbial infections on the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy for vaginal intraepithelial neoplasia.
Vaginal intraepithelial neoplasia (VAIN) is a precancerous condition with significant potential for malignant transformation. The 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is considered as a novel approach to treat VAIN. Recent studies have shown that an imbalance in the vaginal microbiota can affect the progression of VAIN. Thus, the effect of imbalanced microbiota on the efficacy of ALA-PDT for treating VAIN needs to be determined. Sixty-five female patients diagnosed with VAIN were recruited. 5-aminolevulinic acid was applied topically to the vaginal wall, followed by 635 nm red light at intervals of 7-14 days. Cytological inspections, high risk human papillomavirus (HR-HPV) genotyping, vaginal colposcopy examinations, histopathology and culture and identification of vaginal microflora were performed before and after treatment. Among the 62 patients, the complete remission rate (CRR) of vaginal wall lesions was 85.5 %, and the HR-HPV clearance rate was 61.3 %. In the balanced vaginal microbiota group, the CRR of vaginal wall lesions reached 97.2 %, with an HR-HPV clearance rate of 75.1 %. In the imbalanced vaginal microbiota group, the CRR of vaginal wall lesions was only 65.5 %, with an HR-HPV clearance rate of 48.3 %. There was a trend of improved clearance of lesions and HR-HPV when the vaginal microbiota was balanced (p= 0.002 and p= 0.038, respectively). During the process of clinical treatment and the 1-year follow-up period, all patients experienced minimal adverse reactions. The findings of this study demonstrate that ALA-PDT is a clinically effective and safe treatment for VAIN, and the vaginal microbiota's status is a key factor affecting the efficacy of ALA-PDT for VAIN.
vaccines
2026-07-06 | Human Papillomavirus Infection in Patients With VaIN and Vaginal Cancer: A Retrospective Cross-Sectional Study.
Vaginal cancer is a rare malignancy, and the research on it is not comprehensive yet. To explore the characteristics of human papillomavirus (HPV) infection in patients with vaginal intraepithelial neoplasia (VaIN) and vaginal cancer. This study included patients who underwent colposcopy and biopsy of suspected sites at the Second Hospital of Shanxi Medical University from January 2014 to December 2023 due to abnormal cytology results and/or positive HPV test. Those diagnosed with benign inflammatory reaction of the vagina (ie, vaginitis), VaIN and vaginal cancer according to histologic results were selected as the study objects. Clinical data such as age, menopause, clinical manifestations and previous screening history were collected. We aimed to analyze the distribution and characteristics of HPV in VaIN and vaginal cancer patients. A total of 5,180 patients were included in this study. Of the total, 2,739 patients had VaIN1, 641 had VaIN2/3, and 251 had vaginal cancer. There were 235 patients with vaginal squamous cell carcinoma (VaSCC) and 16 patients with vaginal adenocarcinoma. A total of 4,548 patients were infected with HPV. The HPV positive rate was 95.5% in VaIN2/3, 86.0% in VaSCC and 43.8% in adenocarcinoma of the vagina. The most common 5 HPV types were HPV16, 52, 58, 53, and 18. The positive rate of HPV18 in the adenocarcinoma of the vagina was the highest. HPV16, 52, 58, 53, and 18 are the predominant genotypes in VaIN and vaginal cancer in Shanxi, China. HPV testing provides additional benefits for the detection of vaginal lesions during cervical cancer screening. Active HPV vaccination may help reduce the burden of these lesions.
2022-09-23 | Vaccination with human alphapapillomavirus-derived L2 multimer protects against human betapapillomavirus challenge, including in epidermodysplasia verruciformis model mice.
Human alphapapillomaviruses (αHPV) infect genital mucosa, and a high-risk subset is a necessary cause of cervical cancer. Licensed L1 virus-like particle (VLP) vaccines offer immunity against the nine most common αHPV associated with cervical cancer and genital warts. However, vaccination with an αHPV L2-based multimer vaccine, α11-88x5, protected mice and rabbits from vaginal and skin challenge with diverse αHPV types. While generally clinically inapparent, human betapapillomaviruses (βHPV) are possibly associated with cutaneous squamous cell carcinoma (CSCC) in epidermodysplasia verruciformis (EV) and immunocompromised patients. Here we show that α11-88x5 vaccination protected wild type and EV model mice against HPV5 challenge. Passive transfer of antiserum conferred protection independently of Fc receptors (FcR) or Gr-1+ phagocytes. Antisera demonstrated robust antibody titers against ten βHPV by L1/L2 VLP ELISA and neutralized and protected against challenge by 3 additional βHPV (HPV49/76/96). Thus, unlike the licensed vaccines, α11-88x5 vaccination elicits broad immunity against αHPV and βHPV.
2018-09-24 | Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial.
Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543. Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0-99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related. The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide. Merck & Co, Inc.
2016-07-27 | 9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV.
Human papillomavirus (HPV) is the causative agent of nearly all cervical cancer cases as well as a substantial proportion of anal, vulvar, vaginal, penile and oropharyngeal cancers, making it responsible for approximately 5% of the global cancer burden. The first-generation HPV vaccines that is, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine were licensed in 2006 and 2007, respectively. A second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage was initiated even before the first vaccines were approved. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70 to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85-95% of HPV-related vulvar, vaginal and anal cancers. Overall, the 9vHPV vaccine addresses a significant unmet medical need, although further health economics and implementation research is needed.
2015-06-05 | Human papillomavirus burden in different cancers in Iran: a systematic assessment.
Certain types of human papillomaviruses (HPVs) are undoubtedly involved in genesis of human malignancies. HPV plays an etiological role in cervical cancer, but also in many vaginal, vulvar, anal and penile cancers, as well as head and neck cancers. In addition, a number of non-malignant diseases such as genital warts and recurrent respiratory papillomatosis are attributable to HPV. Moreover, HPV forms have detected in several other cancers including esophageal squamous cell carcinoma, lung, prostate, ovarian, breast, skin, colorectal and urinary tract cancers, but associations with etiology in these cases is controversial. The aim of this systematic assessment was to estimate the prevalence of HPV infection and HPV types in HPV-associated cancers, HPV-related non-malignant diseases and in cancers that may be associated with HPV in Iran. The present investigation covered 61 studies on a variety of cancers in Iranian populations. HPV prevalence was 77.5 % and 32.4% in cervical cancer and head and neck cancers, respectively. HPV was detected in 23.1%, 22.2%, 10.4%, 30.9%, 14% and 25.2% of esophageal squamous cell, lung, prostate, urinary tract cancers, breast and skin cancers, respectively. HPV16 and 18 were the most frequent HPV types in all cancers. The findings of present study imply that current HPV vaccines for cervical cancer may decrease the burden of other cancers if they are really related to HPV.
antibodies
2026-05-28 | Beyond extrapolation: Immunotherapy outcomes in recurrent vulvovaginal carcinoma.
To evaluate the efficacy, survival outcomes, and toxicity of immune checkpoint inhibitors (ICI) in patients with recurrent vulvar and vaginal carcinomas (VVC). This retrospective cohort study included patients with recurrent VVC treated with ICI at a single tertiary care center between August 2016 and September 2025. Treatment response was assessed using RECIST 1.1 criteria. Objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were evaluated. Survival outcomes were estimated using the Kaplan-Meier method. Twenty-one patients with recurrent VVC received ICI therapy, with a median age of 73.0 years (IQR, 62.4-77.9); 17 were evaluable for response. PD-L1 expression was positive (CPS ≥1) in 85.7% (n = 18). Pembrolizumab was the most administered ICI (76.2%, 16/21), and most patients received ICI monotherapy (66.7%, 14/21). The median number of ICI cycles was 4 (IQR, 2-6). The ORR was 29.4% (n = 5) with a median DOR of 14.0 months (IQR, 4.97-16.0). Median PFS was 3.0 months (95% CI 1.9-3.4) and median OS was 4.6 months (95% CI 3.7-8.5). Median PFS was 3.1 months for patients receiving combination therapy and 2.5 months for those receiving monotherapy (p = 0.50). Immune-related adverse events occurred in 38.1% (n = 8), including grade ≥ 3 events in 19.0% (n = 4). Disease progression was the most common reason for treatment discontinuation (57.1%, n = 12). ICI demonstrated modest activity in recurrent VVC, with durable responses observed in a small subset of patients. Although survival outcomes were limited overall, ICI therapy may provide meaningful benefit for select patients.
2026-01-20 | A Labial Mass Demonstrated With Sonography and MRI Diagnostic Correlation
Vaginal and labial masses are uncommon and can have a wide range of differentials, both benign and malignant. Included in these masses are hemangiomas, papillomas, mucosal polyps, leiomyomas, and carcinomas. A case report is presented of a patient with a history of surgically treated squamous cell carcinoma, of the vaginal wall, who returned years later with a new palpable labial mass. The initial sonogram pertaining to the new palpable lump showed what was believed may be an irregular, hypoechoic structure, with internal vascularity. A second sonogram conducted several weeks later, in the same region, revealed different findings. The same area imaged several weeks earlier, reevaluated with sonography, demonstrated an ovoid-shaped complex fluid collection with an irregular margin. It contained multiple lacy septa and reflections, without evidence of internal arterial or venous flow. The mass was suspected to be a probable hematoma; however, a magnetic resonance imaging examination was conducted a few days later and the results characterized the mass as a seroma.
2026-01-01 | Feasibility study of photoimmunotherapy combination with ASP-1929 for vulvar, vaginal, and cervical cancer
OBJECTIVE: The aim of this study was to evaluate the feasibility of photoimmunotherapy (PIT) using ASP-1929, an anti-epidermal growth factor receptor (EGFR) antibody-dye conjugate, for vulvar, vaginal, and cervical cancers by validating EGFR expression and establishing immunohistochemistry (IHC)-based eligibility criteria for a phase II trial, HICARi study. METHODS: Cetuximab-binding activity was analyzed in gynecologic cancer cell lines (CaSki, HeLa, and Ishikawa) using flow cytometry and compared with positive controls (A431 and BxPC-3) and a low-EGFR control (MCF-7). IHC was performed on cell blocks and clinical specimens of vulvar, vaginal, and cervical cancers (validation cohort, n=27; screening cohort, n=40). RESULTS: CaSki demonstrated comparable or higher EGFR binding than BxPC-3, whereas HeLa and Ishikawa showed weaker binding. IHC staining intensity correlated with flow cytometry findings. Squamous cell carcinomas consistently exhibited moderate-to-strong EGFR expression, whereas non-squamous carcinomas displayed variable expression. EGFR positivity was defined as >30% of tumor cells with at least moderate membranous staining (2+ or 3+). In the validation cohort, EGFR positivity was observed in 71.4% of the vulvar, 80.0% of the vaginal, and 87.5% of the cervical cancers. The screening cohort showed similar rates: 88.9% of vulvar, 100% of vaginal, and 75.0% of cervical cancers. CONCLUSION: We demonstrated correlation between cetuximab-binding and IHC staining intensity, establishing IHC criteria (≥2+) for patient selection. EGFR positivity (71.4%-87.5%) indicates substantial eligibility for ASP-1929 PIT. Therapeutic efficacy will be evaluated in the HICARi study.
2025-05-28 | Phase 2 dose expansion of START-001: A phase 1/2 study of invikafusp alfa (STAR0602), a first-in-class, selective T cell receptor (TCR)-targeting, bifunctional antibody-fusion molecule, as monotherapy in patients with antigen-rich tumors resistant to anti-PD(L)-1.
TPS2687 Background: Many patients do not respond to anti-PD(L)-1-based therapies and most responders eventually develop resistance. Thus, the development of effective therapies for anti-PD(L)-1 resistance is a significant unmet medical need. Invikafusp, a selective, dual T cell agonist targeting Vβ6/Vβ10 T cells, is being evaluated in START-001: a multicenter Phase 1/2 monotherapy trial in patients with anti-PD(L)1-resistant, antigen-rich (TMB-H, MSI-H/dMMR, or virally associated) solid tumors. The completed Phase 1 dose escalation of intravenous invikafusp, Q2W, per 3+3 design, identified a recommended Phase 2 dose (RP2D) of 0.08 mg/kg, and demonstrated clinically meaningful single-agent anti-tumor activity in patients with anti-PD(L)-1 resistant tumors, including confirmed partial responses in TMB-H, microsatellite stable, colorectal cancer (CRC) patients with one durable response lasting ~12 months. It promoted potent and selective expansion of mainly CD8+ Vβ6/ Vβ10 T cells with a novel central memory T cell phenotype, and led to ctDNA decrease and expansion of antigen-specific T cells. Based on these results, the US FDA granted Fast Track Designation for invikafusp in TMB-H CRC. Methods: Study design: Using an optimal Simon’s 2 stage design, Phase 2 of START-001 is a dose expansion at the RP2D, to further investigate the safety and anti-tumor activity of invikafusp in 9 cohorts of patients who have the following solid tumors: 1) tissue-agnostic, TMB-H; 2) tissue-agnostic, dMMR/MSI-H; 3) CRC (both Ras wild-type and mutant) TMB-H and/or MSI-H/dMMR); 4) virally associated tumors such as Merkel cell carcinoma, cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers, or EBV-related solid tumors; 5) metastatic triple-negative breast cancer; 6) platinum-resistant epithelial ovarian cancer; 7) metastatic castration-resistant prostate cancer; 8) primary stage IV or recurrent non-small cell lung cancer; and 9) immunogenic tumors (e.g., cSCC, melanoma and RCC). Major Eligibility criteria: ≤ 3 lines of prior cancer therapies [anti-PD(L)-1s allowed] for advanced or metastatic disease; intolerance to standard therapies including anti-PD(L)-1s allowed; no liver metastases or adequately treated liver metastases either locally (e.g., by surgery, radiofrequency ablation, or chemoembolization) or systemically and stable for 3 months. Primary objective: to further evaluate anti-tumor activity of invikafusp as monotherapy in each of the above-described 9 cohorts of patients with anti-PD(L)-1-resistant, unresectable, locally advanced, or metastatic solid tumors. Primary endpoint: overall response rate (ORR) per iRECIST. The enrollment to the first three cohorts has begun. Clinical trial information: NCT05592626 .
2025-04-26 | Advances and Challenges in the Treatment of HPV-Associated Lower Genital Tract Cancers by Immune Checkpoint Blockers: Insights from Basic and Clinical Science.
Human papillomavirus (HPV)-related lower genital cancers, including cervical cancer, anal squamous cell carcinoma (SCC), vaginal cancer, vulvar cancer, and penile cancer, pose a significant health burden, with approximately 45,000 new cases diagnosed annually. Current effective treatment modalities include chemoradiotherapy, systemic chemotherapy, and immune checkpoint inhibitors (ICIs). The tumor microenvironment in HPV-related cancers is characterized by immune evasion mechanisms, including the modulation of immune checkpoints such as PD-L1/PD-1. HPV oncoproteins E5, E6, and E7 play crucial roles in this process, altering the expression of immune inhibitory molecules and the recruitment of immune cells. ICIs, such as programmed cell death protein 1 (PD-1) inhibitors, have shown efficacy in enhancing the immune response against HPV-associated tumors by blocking proteins that allow cancer cells to evade immune surveillance. Recent studies have demonstrated that HPV-positive tumors exhibit a more favorable response to ICI-based therapies compared to HPV-negative tumors. The integration of ICIs into treatment regimens for HPV-related cancers has been supported by several clinical trials. The inclusion of ICIs in the treatment approach for HPV-related lower genital cancers presents a promising opportunity for improving patient outcomes. Ongoing research and clinical trials are advancing our understanding of the immune microenvironment and the therapeutic potential of immunotherapy for these cancers.
oligonucleotides
2025-07-28 | DNA methylation testing for vulvar cancer risk stratification in patients with high-grade vulvar intraepithelial neoplasia: a population-based cohort study.
High-grade vulvar intraepithelial neoplasia (VIN) is the precursor of vulvar cancer. The main variants are human papillomavirus (HPV)-associated high-grade squamous intraepithelial lesion (HSIL) and HPV-independent VIN, often clinically referred to as differentiated VIN (dVIN) and associated with vulvar dermatoses, usually lichen sclerosus. Surgical treatment of high-grade VIN often leads to genital deformity, impaired sexual function and reduced quality of life. To optimize clinical management, accurate biomarkers providing information on the cancer risk of high-grade VIN are needed. To investigate the prognostic value of a three-gene methylation marker panel and other potential risk factors for the risk of progression to cancer in patients with HSIL and dVIN. From a population-based cohort of patients diagnosed with high-grade VIN, patients with a histopathologically confirmed diagnosis of HSIL (n = 578) and dVIN (n = 46) were selected. All lesions were tested by a three-gene methylation panel including the genes ZNF582, SST and miR124-2. The vulvar cancer risk and the prognostic value of methylation status, age, HPV genotype, wild-type vs. mutant p53 immunohistochemistry status and presence of lichen sclerosus were estimated by Kaplan-Meier and Cox regression, respectively. Vulvar cancer developed in 26 of 578 patients with HSIL (4.5%) and in 21 of 46 with dVIN (46%) within 5 years. In HSIL, positive methylation status was identified as the only prognostic factor for vulvar cancer development [hazard ratio (HR) 4.87, 95% confidence interval (CI) 1.20-21.45]. The prognostic value of methylation remained present when selecting patients who did not receive radical surgical excision as their primary treatment. In this group, the 5-year cancer risk was 7.7% in methylation-positive HSIL and 1.4% in methylation-negative HSIL (P = 0.008). In dVIN, mutant p53 status was the sole prognostic risk factor for progression to cancer (HR 7.67, 95% CI 1.78-33.08). Despite wide CIs, the three-gene methylation test serves as a promising prognostic tool for cancer risk stratification in patients with vulvar HSIL. Patients with methylation-negative HSIL carry a low cancer risk, allowing for more conservative management strategies. This approach may help avoid overtreatment, reducing morbidity and improving quality of life.
2021-11-23 | Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma
Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.
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