(MCRC Clinical) An integrated digital pathology and functional tissue study of risk stratification in penile squamous cell carcinoma

About the project

About the Project Penile squamous cell carcinoma (PSCC) is a rare malignancy in which surgery is the main treatment modality. However, patients suffer substantial physical, psychological and sexual morbidity. There is a need for reproducible biomarkers that can identify patients at sufficiently low risk of inguinal nodal disease to consider less morbid, penile-preservation management strategies, including loco-regional radiotherapy for cure. PSCCs harbour two distinct clinicopathological entities as defined by the WHO 2022 guidelines: HPV-associated (and therefore p16 immunohistochemistry positive) and HPV-independent1 with p16 positivity predicting more favourable outcomes 2,3. However p16-HPV status and the partially subjective clinical pathology features (i.e. lesion grade & depth, lymphovascular and perineural invasions) do not capture tumour microenvironment (TME; immune, stromal cells and hypoxic sub-regions) heterogeneity nor uniformly predict inguinal metastases 4,5,6. This project will develop a reproducible digital and spatial pathology model for PSCC inguinal nodal metastasis to generate the evidence and framework for future prospective multidisciplinary and biomarker-driven preservation treatments Central hypothesis Quantitative PSCC features of tumour–stroma organisation (tumour budding, pattern of invasion); immune-cell distribution (Tumour Infiltrating Lymphocytes; TILs), coupled with spatial transcriptomics, provides a signature for low risk of inguinal nodal involvement and excellent radioresponse. Primary aim To develop a clinically calibrated digital pathology-based risk stratification for predicting inguinal nodal metastasis and potential cure with radiotherapy in PSCC. Additional/Secondary aims Define spatial and molecular features associated with pathology-derived low and high-risk nodal states Compare risk-state features between matched primary/inguinal lymph-node tumours Establish ex vivo models (organoids) of primary for experimental therapeutics Research questions Can quantitative digital and spatial pathology improve prediction of inguinal nodal metastasis? Are their pathology-defined low/high risk states for inguinal lymph-node metastasis? Can patient-derived tissue primary and metastatic models be propagated in vitro and in vivo to provide for the testing of radiotherapy response. Eligibility You must be a post-registration clinician and therefore must hold an MBChB degree or equivalent medical degree and ideally have a specialist post in a related subject, to apply for our Clinical Research Training Fellowships. It is generally expected that CRTFs will return to a training programme in the UK upon completion of their research degree. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English language) before contacting potential supervisors to express an interest in their project. Eligibility information can be found on the University's Country Specific information page. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply Apply directly via this link: https://tinyurl.com/577zjazd or on the online application portal, select MCRC PhD Programme as the programme of study. You may only apply for one project within this scheme. Please ensure that your application includes all required supporting documents: Curriculum Vitae (CV) Supporting Statement Academic Certificates and Transcripts Incomplete or late applications will not be considered. Further details are available on our website: CRUK Manchester Centre PhD Training Scheme | Biology, Medicine and Health | University of Manchester Application Timeline Applications open: Monday, 5 October 2026 Application deadline: Monday, 23 November 2026 Interview date: Week commencing 11 January 2027 Start date: September 2027 Equality, diversity and inclusion are central to the University’s activities. The full statement can be found here: https://www.bmh.manchester.ac.uk/study/research/getting-started/equality-diversity-inclusion/”

Research areas