Article
Oncology
Nikki B. Thuijs, Marc van Beurden, Annette H. Bruggink, Renske D. M. Steenbergen, Johannes Berkhof, Maaike C. G. Bleeker
Summary: The study found that the risk of vulvar squamous cell carcinoma (VSCC) is considered lower in high-grade squamous intraepithelial lesion (HSIL) compared to differentiated vulvar intraepithelial neoplasia (dVIN), but more research is needed for confirmation. The incidence of high-grade VIN and cumulative VSCC risk is higher in dVIN compared to HSIL, with independent risk factors including type of VIN, age, and presence of lichen sclerosis. Recognition and early identification of patients with high-risk VIN, particularly dVIN, is crucial.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Oncology
Maria-Eulalia Fernandez-Montoli, Fatima Heydari, Fabrizia Lavecchia, Miquel-Angel Pavon, Esther Guerra, Xavier Matias-Guiu, Maria-Dolores Marti, Sara Tous
Summary: This retrospective study aimed to assess the long-term response to imiquimod in patients with vulvar HSIL and to analyze the role of HPV in the persistence or recurrence of vulvar HSIL after imiquimod treatment. The results showed that imiquimod effectively treated vulvar HSIL, with a higher number of complete and partial responses. Patients who had a partial or no response to imiquimod had a higher risk of recurrence, especially in immunosuppressed patients. The study also found that patients who tested positive for HPV after imiquimod treatment were more likely to experience recurrence.
Article
Oncology
Nikki B. Thuijs, Johannes Berkhof, Mujde Ozer, Sylvia Duin, Annina P. van Splunter, Barbara C. Snoek, Danielle A. M. Heideman, Marc van Beurden, Renske D. M. Steenbergen, Maaike C. G. Bleeker
Summary: The study found that vulvar squamous cell carcinoma is associated with increased DNA methylation, and higher DNA methylation levels in high-grade vulvar intraepithelial neoplasia seem to reflect a higher cancer risk. DNA methylation markers may have high potential in the diagnostic workup of vulvar intraepithelial neoplasia, and longitudinal studies are needed to verify their prognostic value as a clinical tool.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Oncology
Nikki B. Thuijs, Willemijn A. M. Schonck, Linde L. J. Klaver, Guus Fons, Marc van Beurden, Renske D. M. Steenbergen, Maaike C. G. Bleeker
Summary: In this exploratory study, biomarker profiles in patients with multiple high-risk HPV-associated vulvar precursor lesions were compared. While the biomarkers generally showed similar expression between lesions, marked differences were occasionally observed, indicating heterogeneity within multifocal lesions. This study contributes to a better understanding of the potential diagnostic, prognostic, and predictive value of biomarkers in patients with multifocal HSIL.
Article
Pathology
Emily F. Thompson, Richard W. C. Wong, Giorgia Trevisan, Basile Tessier-Cloutier, Noorah Almadani, Julia Chen, Angela Cheng, Anthony Karnezis, Melissa K. McConechy, Amy Lum, Janine Senz, Jessica N. McAlpine, David G. Huntsman, Blake Gilks, Amy Jamieson, Lynn N. Hoang
Summary: Abnormal p53 immunohistochemical staining patterns are found in vulvar squamous cell carcinoma and differentiated vulvar intraepithelial neoplasia. This study evaluated the use of p53 immunohistochemical staining at margins and its impact on local recurrence rates.
Article
Medicine, General & Internal
Mateusz Bujko, Kamil Zalewski, Martyna Szczyrek, Artur Kowalik, Joanna Boresowicz, Angelika Dlugosz, Krzysztof Goryca, Stanislaw Gozdz, Magdalena Kowalewska
Summary: This study investigated the diagnostic value of circulating hsa-miR-431-5p in vulvar precancers and VSCC. Higher levels of miR-431-5p were observed in VSCC patients compared to those with vulvar precancers, and its levels were predictive of survival rates in VSCC patients.
Article
Oncology
Jingjing Xiao, Ziren Chen, Yinping Xiao, Long Sui, Chao Wang, Qing Cong
Summary: This study investigated the depth of vulvar intraepithelial neoplasia (VIN) and its involvement of skin appendages, providing evidence for laser surgery. The results showed that the thickness of VIN lesions was generally less than or equal to 1 mm, but could reach approximately 3 mm when extending onto hairy areas, leading to the destruction of involved skin appendages.
FRONTIERS IN ONCOLOGY
(2023)
Article
Obstetrics & Gynecology
Monica J. Janke, Jennie DeBlanc, Emily K. Kobernik, Stephanie L. Skala, Guadalupe Lorenzatti Hiles, Rebeca Kelly, Kathryn C. Welch
Summary: This study suggests that treating lichen sclerosus with high-potency topical corticosteroids does not increase the risk of high-grade squamous intraepithelial lesion recurrence in patients with comorbid vulvar lichen sclerosus and high-grade squamous intraepithelial lesion.
JOURNAL OF LOWER GENITAL TRACT DISEASE
(2022)
Review
Ophthalmology
Ingvild Ramberg, Michael Moller-Hansen, Peter Bjerre Toft, Mikkel Funding, Steffen Heegaard
Summary: This study aimed to investigate the prevalence of HPV in conjunctival intraepithelial neoplasia and carcinoma, as well as explore the relationship between geographical differences or detection modalities and the development of the disease. The findings showed that HPV infection increases the risk of conjunctival intraepithelial neoplasia and carcinoma, with HPV16, 18, and 33 being the most common genotypes, suggesting that HPV vaccines currently available may prevent most HPV-related diseases.
ACTA OPHTHALMOLOGICA
(2021)
Article
Medicine, Research & Experimental
Xiao Tang, Huina Zhang, Tiannan Wang, Wei Jiang, Terri E. Jones, Yanmei He, Lei Li, Lingling Tong, Cheng Wang, Wei Wang, Kaixuan Yang, Rutie Yin, Chengquan Zhao
Summary: Coinfection with multiple high-risk human papillomavirus (hrHPV) is frequently observed in cervical specimens. The clinical significance of concomitant multiple hrHPV infections is poorly understood, and published results are inconsistent. This study found that multiple hrHPV infections do not carry an increased risk for developing cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma compared to single hrHPV infections.
LABORATORY INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Cornelia Peterson, Rupin N. Parikh, Meleha T. Ahmad, Ashley A. Campbell, Yassine Daoud, Nicholas Mahoney, Sepideh Siadati, Charles G. Eberhart
Summary: In-situ hybridization is a convenient and reliable method for detecting human papillomavirus infection in formalin-fixed paraffin-embedded tissue. This study found that RNA in-situ hybridization is effective in detecting HPV infection in squamous lesions of the conjunctiva and can help distinguish between reactive atypia and true dysplasia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhiwei Liu, Ruibing Su, Anil Ahsan, Chencai Liu, Xiaoqi Liao, Dongping Tian, Min Su
Summary: Squamous esophageal carcinoma is a common pathological type of esophageal carcinoma worldwide, with genomic instability observed during its development. This study suggests that DNA mutations caused by early DNA damage may serve as an indicator for ultra-early screening of esophageal cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Shatavisha Dasgupta, Patricia C. Ewing-Graham, Sigrid M. A. Swagemakers, Thierry P. P. van den Bosch, Peggy N. Atmodimedjo, Michael M. P. J. Verbiest, Marit de Haan, Helena C. van Doorn, Peter J. van der Spek, Senada Koljenovic, Folkert J. van Kemenade
Summary: Vulvar squamous cell carcinoma (VSCC) is the most common form of vulvar malignancy, and a molecular characterization of VSCC is crucial for diagnosis and treatment. Through genome-wide methylation sequencing, this study identified 199 genes with differential methylation in VSCC, most of which are hyper-methylated and involved in transcription regulator activity, suggesting their importance in VSCC development. Further exploration of the prognostic relevance of these genes in larger cohorts is warranted.
Article
Cell Biology
Y. Ariel Liu, Jennifer X. Ji, Noorah Almadani, Richard Crawford, C. Blake Gilks, Mary Kinloch, Lien Hoang
Summary: Strong and uniform p53 staining in basal cells, extending into the parabasal layers, and complete absence of staining (null type) is helpful in distinguishing dVIN from other mimics in the vulva. p53 staining of lesser intensity or quantity, particularly basal overexpression only, overlaps with that in vulvar inflammatory lesions.
Review
Oncology
Feline O. Voss, Nikki B. Thuijs, Ravi F. M. Vermeulen, Erica A. Wilthagen, Marc van Beurden, Maaike C. G. Bleeker
Summary: Patients with differentiated vulvar intraepithelial neoplasia have a high risk of developing vulvar squamous cell carcinoma, with rapid cancer progression. Increased awareness, timely recognition, aggressive treatment, and close follow-up are strongly recommended for HPV-independent vulvar conditions including dVIN.
Review
Oncology
Jan M. Van Rees, Lissa Wullaert, Alexander A. J. Grueter, Yassmina Derraze, Pieter J. Tanis, Henk M. W. Verheul, John W. M. Martens, Saskia M. Wilting, Geraldine Vink, Jeroen L. A. Van Vugt, Nick Beije, Cornelis Verhoef
Summary: This systematic review and meta-analyses demonstrate a strong association between ctDNA and recurrent disease in non-metastatic rectal cancer. ctDNA analysis can stratify patients into high and low risk groups for recurrence, especially when detected after neoadjuvant treatment and surgery. Future research should focus on the feasibility of ctDNA-guided treatment and follow-up strategies in rectal cancer.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Feline O. Voss, Nikki B. Thuijs, Sylvia Duin, Mujde Ozer, Marc van Beurden, Johannes Berkhof, Renske D. M. Steenbergen, Maaike C. G. Bleeker
Summary: This study aimed to validate the accuracy of previously identified DNA methylation markers for detection of high-grade vulvar intraepithelial neoplasia (VIN). The best-performing individual marker was found to be SST, detecting 80% of high-grade VIN cases, with excellent detection of HPV-independent VIN, known to have the highest cancer risk. Selection of a marker panel including ZNF582, SST, and miR124-2 also yielded high accuracy for detection of high-grade VIN.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Khrystany T. Isebia, Bianca Mostert, Teoman Deger, Jaco Kraan, Vanja de Weerd, Esther Oomen-de Hoop, Paul Hamberg, Brigitte C. M. Haberkorn, Helgi H. Helgason, Ronald de Wit, Ron H. J. Mathijssen, Martijn P. Lolkema, Saskia M. Wilting, Job van Riet, John W. M. Martens
Summary: In this study, the researchers found that the abnormal aneuploidy score of cell-free tumor DNA (ctDNA) in the blood can predict the survival of metastatic castration-resistant prostate cancer (mCRPC) patients, making it a potential biomarker.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Manouk K. Bos, Sarah R. Verhoeff, Sjoukje F. Oosting, Willemien C. van der Houven van Oordt, Ruben G. Boers, Joachim B. Boers, Joost Gribnau, John W. M. Martens, Stefan Sleijfer, Carla M. L. van Herpen, Saskia M. Wilting
Summary: For patients with intermediate risk renal cell carcinoma, some have a slow disease progression. Delaying treatment for metastatic disease by entering a watchful waiting period is a safe option for these patients. However, it is currently difficult to identify patients with indolent disease or those with rapidly progressive disease. This study investigates the use of cell-free DNA (cfDNA) as a blood-based biomarker to identify patients with rapid disease progression.
Article
Oncology
Elisabeth M. Jongbloed, Hedwig M. Blommestein, Hannah M. van Schoubroeck, John W. M. Martens, Saskia M. Wilting, Carin A. Uyl-de Groot, Agnes Jager
Summary: The addition of two years of abemaciclib treatment to high-risk ER+, HER2-early breast cancer patients has been approved by the FDA. Using detection of minimal residual disease (MRD) through patient-informed circulating tumor DNA assays, the addition of abemaciclib treatment shows cost-effectiveness for high-risk patients. However, adding abemaciclib to all high-risk patients is not cost-effective, while MRD-guided treatment is more cost-effective compared to standard treatment.
BREAST CANCER-TARGETS AND THERAPY
(2023)
Article
Cell Biology
Nikki B. Thuijs, Marc van Beurden, Sylvia Duin, Danielle A. M. Heideman, Johannes Berkhof, Renske D. M. Steenbergen, Maaike C. G. Bleeker
Summary: This study comprehensively classified and assessed a large series of vulvar lesions, finding that 88.4% of high-grade VIN were associated with HPV and 10.9% were HPV independent. Immunohistochemistry testing for p16INK4a and p53 is important for distinguishing between the two types, which have different cancer risks.
Article
Multidisciplinary Sciences
Elisabeth M. Jongbloed, Maurice P. H. M. Jansen, Vanja de Weerd, Jean A. Helmijr, Corine M. Beaufort, Marcel J. T. Reinders, Ronald van Marion, Wilfred F. J. van IJcken, Gabe S. Sonke, Inge R. Konings, Agnes Jager, John W. M. Martens, Saskia M. Wilting, Stavros Makrodimitris
Summary: Next generation sequencing of cfDNA is a promising method for treatment monitoring and therapy selection in MBC. However, distinguishing tumor-specific variants from sequencing artefacts and germline variation is challenging. To address this, a machine learning model was built to remove false positive variant calls and select tumor-derived variants.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Siyu Fu, Teoman Deger, Ruben G. Boers, Joachim B. Boers, Michael Doukas, Joost Gribnau, Saskia M. Wilting, Jose D. Debes, Andre Boonstra
Summary: In this study, aberrant hypermethylation changes in HOXA1, CLEC11A, AK055957, and TSPYL5 were identified in non-cirrhotic HCC tissues compared to cirrhosis, hepatitis, and benign lesions, providing potential detectable biomarkers for these unusual HCC cases.
Article
Oncology
Ellis L. Eikenboom, Saskia M. Wilting, Teoman Deger, Malgorzata I. Srebniak, Monique Van Veghel-Plandsoen, Ruben G. Boers, Joachim B. Boers, Wilfred F. J. van IJcken, Joost H. Gribnau, Peggy Atmodimedjo, Hendrikus J. Dubbink, John W. M. Martens, Manon C. W. Spaander, Anja Wagner
Summary: We assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood test. The results showed that cfDNA methylation profiles could discriminate all microsatellite instable advanced neoplasia, making it a particularly promising tool for Lynch syndrome surveillance. Larger studies are needed to validate these findings.
Article
Oncology
Lindsay Angus, Marcel Smid, Saskia M. Wilting, Manouk K. Bos, Neeltje Steeghs, Inge R. H. M. Konings, Vivianne C. G. Tjan-Heijnen, Johanna M. G. H. van Riel, Agnes J. van de Wouw, Edwin Cuppen, Martijn P. Lolkema, Agnes Jager, Stefan Sleijfer, John W. M. Martens
Summary: This study investigated the mutated genes and mutation patterns, as well as the expression levels of relevant genes, in 101 breast cancer metastatic lesions with ER-positive tumors. The analyses revealed two distinct patient groups, one showing ongoing, active ER and its associated signal route, and the other showing lower ER expression levels. The study highlights the importance of combining mutation and expression analyses to identify patients who may still benefit from anti-hormonal treatment targeting ER.
Review
Cell Biology
Lissa Wullaert, Jan M. van Rees, John W. M. Martens, Henk M. W. Verheul, Dirk J. Grunhagen, Saskia M. Wilting, Cornelis Verhoef
Summary: This study provides an overview and meta-analysis of the current literature on the value of ctDNA in patients with colorectal liver metastases. The results show a strong association between detectable ctDNA after surgery or completion of adjuvant therapy and oncological outcomes. However, there is no association between detectable ctDNA before surgery and oncological outcomes.
Article
Oncology
Noortje Verschoor, Vanja de Weerd, Mai N. Van, Jaco Kraan, Marcel Smid, Joan B. Heijns, Jan C. Drooger, Johanna M. Zuetenhorst, Annemieke van der Padt-pruijsten, Agnes Jager, Stefan Sleijfer, John W. M. Martens, Saskia M. Wilting
Summary: This study demonstrates that mFAST-SeqS can serve as a strong prognostic marker for MBC patients. It is an affordable and easily implementable method for assessing ctDNA levels, offering an alternative tool for prognosis. The aneuploidy score obtained using mFAST-SeqS is significantly correlated with CTC count and is a significant prognostic marker for both PFS and OS in MBC patients.
Article
Oncology
Laure Nicolai, Refika Yigit, Maaike C. G. Bleeker, Joost Bart, Jacobus van der Velden, Constantijne H. Mom
Summary: For patients with stage IA cervical cancer with a diameter >7 mm, we recommend considering a pelvic lymph node assessment in case of DOI >3 mm and/or presence of LVSI.
JOURNAL OF GYNECOLOGIC ONCOLOGY
(2023)
Article
Oncology
D. M. Mens, J. M. van Rees, S. M. Wilting, C. Verhoef
Summary: Chemoradiation therapy (CRT) is the standard of care for treating rectal cancer, but it can cause damage to the surrounding healthy tissue and not all patients benefit from it. This study aims to develop a diagnostic innovation using DNA methylation to predict the effectiveness of CRT for rectal cancer patients.
Article
Oncology
Noortje Verschoor, Marcel Smid, Agnes Jager, Stefan Sleijfer, Saskia M. Wilting, John W. M. Martens
Summary: In this study, the researchers investigated the characteristics and therapy resistance of HER2-positive breast cancer through integrating genomics and transcriptomics data. They found that the genomic profiles of primary and metastatic HER2-positive breast cancers were similar, and certain genomic features were predictive of progression-free survival on post-biopsy anti-HER2 treatment. Additionally, a HER2-driven expression profile grouped different types of HER2-positive tumors and indicated the possibility of transformation to ER independence. Integrated genomic and transcriptomic analyses may play a key role in establishing therapeutic options.
BREAST CANCER RESEARCH
(2023)