Background: Human papillomavirus (HPV) has been proposed as a potential pathogenetic organism involved in prostate cancer (PCa), but the association between HPV infection and relevant genomic changes in PCa is poorly understood. Methods: To evaluate the relationship between HPV genotypes and genomic alterations in PCa, HPV capture sequencing of DNA isolated from 59 Han Chinese PCa patients was performed using an Illumina HiSeq2500. Additionally, whole-exome sequencing of DNA from these 59 PCa tissue samples and matched normal tissues was carried out using the BGI DNBSEQ platform. HPV infection status and genotyping were determined, and the genetic disparities between HPV-positive and HPV-negative PCa were evaluated. Results: The presence of the high-risk HPV genome was identified in 16.9% of our cohort, and HPV16 was the most frequent genotype detected. The overall mutational burden in HPV-positive and HPV-negative PCa was similar, with an average of 2.68/Mb versus 2.58/Mb, respectively, in the targeted whole-exome region. HPV-negative tumors showed a mutational spectrum concordant with published PCa analyses with enrichment for mutations in SPOP, FOXA1, and MED12. HPV-positive tumors showed more mutations in KMT2C, KMT2D and ERCC2. Copy number alterations per sample were comparable between the two groups. However, the significantly amplified or deleted regions of the two groups only partially overlapped. We identified amplifications in oncogenes, including FCGR2B and CCND1, and deletions of tumor suppressors, such as CCNC and RB1, only in HPV-negative tumors. HPV-positive tumors showed unique deletions of tumor suppressors such as NTRK1 and JAK1. Conclusions: The genomic mutational landscape of PCa differs based on HPV infection status. This work adds evidence for the direct involvement of HPV in PCa etiology. Different genomic features render HPV-positive PCa a unique subpopulation that might benefit from virus-targeted therapy.

Human papillomavirus (HPV) has been recognized as an important risk factor in penile cancer. This study aimed to investigate the HPV subtypes and integration status in Chinese patients. Samples were collected from 103 penile cancer patients aged 24-90 years between 2013 and 2019. We found that HPV infection rate was 72.8%, with 28.0% integration. The aging patients were more susceptible to HPV (p = 0.009). HPV16 was the most frequent subtype observed (52/75) and exhibited the highest frequency of integration events, with 11 out of 30 single infection cases showing integration positive. The HPV integrations sites in the viral genome were not randomly distributed, the breakpoints were enriched in the E1 gene (p = 0.006) but relatively scarce in L1, E6 and E7. Our research might provide some clues how HPV leads to the progression of penile cancer.

Upper tract urothelial carcinoma (UTUC) is a rare and aggressive malignancy, accounting for only 5–10% of all urothelial carcinomas (UCs). Lung, bone, liver, and distant lymph nodes are common sites of metastasis, while gastrointestinal metastasis is extremely rare. We present a case of a 63-year-old female who developed a descending colon lesion 19 months after left radical nephroureterectomy for high-grade ureteral UC. The diagnosis was established by computed tomography (CT), magnetic resonance imaging (MRI), colonoscopy, and biopsy, which excluded primary colorectal malignancy. First-line therapy consisted of six 21-day cycles of gemcitabine plus cisplatin, followed by two cycles of tislelizumab maintenance immunotherapy. Restaging with contrast-enhanced CT and positron emission tomography/computed tomography (PET/CT) demonstrated disease progression. Despite switching to second-line nab-paclitaxel, the patient rapidly deteriorated from tumor cachexia and ultimately succumbed to septic shock secondary to severe pulmonary infection. This represents the first reported case of descending colon metastasis from primary ureteral UC. It highlights the colon as a potential metastatic site where biopsy is essential for definitive diagnosis. Notably, although the patient initially responded to platinum-based therapy, the subsequent rapid progression underscores the need for vigilant monitoring and timely adjustment of therapeutic strategies in managing such high-risk presentations.