-
The British Journal of Dermatology Jun 2024The structured expression of several keratins in the skin is associated with differentiation status of the epidermal layers, whereas others are upregulated only during...
BACKGROUND
The structured expression of several keratins in the skin is associated with differentiation status of the epidermal layers, whereas others are upregulated only during wound healing, in skin disorders and in cancers. One of these stress keratins, K17, is correlated with poor prognosis in various cancer types and its loss has been shown to decelerate tumour growth. K17 expression can also be detected in cutaneous squamous cell carcinomas (SCCs), where UV-irradiation and infection with cutaneous human papillomaviruses (HPVs) are important co-factors. It was previously reported that K17 is upregulated in papillomavirus (PV)-induced benign skin lesions in mice and induces an immunological status that is beneficial for tumour growth.
OBJECTIVES
In order to investigate whether K17 upregulation is induced by PVs, we analysed K17 levels in skin tumour specimens of different animal models and humans.
METHODS
Various immunofluorescence stainings were performed to identify K17 expression as well as levels of E-Cadherin, vimentin and CD271. Tissues were further analysed by PCRs, qPCRs and ELISA to control for PV activity. K17knockdown cells were generated and effects on viral life cycle were investigated by infection assays, qPCR and Western blotting.
RESULTS
We could show that K17 is commonly expressed in skin tumours and that its presence is not directly linked to viral oncoprotein expression. Rather, K17 expression seems to be a marker of epithelial differentiation and its absence in tumour tissue is associated with an epithelial-to-mesenchymal transition. We further showed that the absence of K17 in skin tumours increases markers of cancer stem-like cells and negatively affects viral protein synthesis.
CONCLUSIONS
Collectively, our data indicate that K17 expression is a common feature in skin tumourigenesis. While it is not primarily targeted by PV oncoproteins, our in vivo and in vitro data suggest that it is an important regulator of epithelial differentiation and thus may play a role in controlling viral protein synthesis.
PubMed: 38878280
DOI: 10.1093/bjd/ljae255 -
Experimental and Therapeutic Medicine Aug 2024Squamous papilloma is a benign neoplasm that originates from the stratified squamous epithelium of the mucous membrane. Its principal etiological factor is human...
Squamous papilloma is a benign neoplasm that originates from the stratified squamous epithelium of the mucous membrane. Its principal etiological factor is human papillomavirus infection, with a predilection for manifesting within the oral cavity. Squamous papilloma predominantly affects regions on the palate, cheeks, lips and tongue. However, to the best of our knowledge, the occurrence of squamous papilloma within the confines of the mandible remains unreported hitherto. The present report documents a case of squamous papilloma involving the mandible who was managed at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) in January 2023. The patient underwent a series of recurrent jaw inflammations, manifesting with malignant imaging characteristics. Subsequent pathological analysis confirmed a diagnosis of papilloma in the jaw. The present report highlights the pivotal role of prolonged inflammation in the genesis of jaw squamous papilloma, prompting avenues for further investigation, including the potential of inflammation to induce aberrant cell growth, mediate cell interactions, orchestrate cytokine actions and influence stress mediators. In addition, the current study posits a plausible connection between persistent inflammation, compromised epithelial integrity and an increased likelihood of head and neck papilloma, particularly concerning human papillomavirus infection. This article delineates the clinical attributes of the uncommon manifestations of jaw papilloma and delves into the associated mechanisms, thereby contributing to an enhanced comprehension of jaw disorders. This comprehensive insight equips clinicians with a heightened knowledge base for more precise diagnosis and treatment of analogous cases.
PubMed: 38873042
DOI: 10.3892/etm.2024.12590 -
Clinical Gastroenterology and... Jun 2024Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and... (Review)
Review
BACKGROUND AND AIMS
Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.
METHODS
We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach.
RESULTS
Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on six structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with longstanding (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus(SCCA) and anorectal carcinoma. Risk factors for SCCA, notably human papilloma virus (HPV), should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an exam under anesthesia (EUA) with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers.
CONCLUSION
Inflammatory bowel disease (IBD) clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.
PubMed: 38871152
DOI: 10.1016/j.cgh.2024.05.029 -
Photodiagnosis and Photodynamic Therapy Jun 2024Anal condyloma acuminatum (CA) is marked by its thorny treatment and high recurrence rate. Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrates...
A nomogram to predict anal condyloma acuminatum recurrence in HIV-negative patients following photodynamic therapy: A decade-long retrospective clinical study at a single tertiary hospital.
BACKGROUND
Anal condyloma acuminatum (CA) is marked by its thorny treatment and high recurrence rate. Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrates significant efficacy and safety in treating anal CA, it does not completely prevent recurrence. This study aimed to develop and validate a nomogram model in predicting the risk of relapse in HIV-negative patients with anal CA following treatment with ALA-PDT.
METHODS
A retrospective analysis was conducted on patients diagnosed with anal CA who received combined CO laser vaporization and ALA-PDT between January 2013 and May 2023. Patients were divided into recurrence and non-recurrence groups. A nomogram was developed based on factors showing statistical significance in multivariable logistic regression analysis. The discriminative ability and clinical utility of the nomogram were assessed via ROC curves and decision curve analysis, with internal validation performed through bootstrap resampling.
RESULTS
Among the 176 patients included, 33 (18.75 %) experienced recurrence, while 143 did not. Independent predictors for recurrence included HPV types, history of anal intercourse, and the number of CO laser treatments received. Incorporating these predictors, the nomogram demonstrated a superior diagnostic performance (area under the curve = 0.881, 95 % CI: 0.818-0.935) and a significant net benefit in decision curve analysis.
CONCLUSIONS
The nomogram accurately predicts the risk of recurrence in HIV-negative patients with anal CA following ALA-PDT. It offers a valuable tool for guiding preoperative clinical decision-making and establishing personalized treatment strategies to minimize the risk of relapse.
PubMed: 38871015
DOI: 10.1016/j.pdpdt.2024.104245 -
Molecular Carcinogenesis Jun 2024To study mechanisms driving/inhibiting skin carcinogenesis, stage-specific expression of 14-3-3σ (Stratifin) was analyzed in skin carcinogenesis driven by activated...
To study mechanisms driving/inhibiting skin carcinogenesis, stage-specific expression of 14-3-3σ (Stratifin) was analyzed in skin carcinogenesis driven by activated ras/fos expression (HK1.ras/fos) and ablation of PTEN-mediated AKT regulation (K14.creP/Δ5PTEN). Consistent with 14-3-3σ roles in epidermal differentiation, HK1.ras hyperplasia and papillomas displayed elevated 14-3-3σ expression in supra-basal keratinocytes, paralleled by supra-basal p-MDM2 activation and sporadic p-AKT expression. In bi-genic HK1.fos/Δ5PTEN hyperplasia, basal-layer 14-3-3σ expression appeared, and alongside p53/p21, was associated with keratinocyte differentiation and keratoacanthoma etiology. Tri-genic HK1.ras/fos-Δ5PTEN hyperplasia/papillomas initially displayed increased basal-layer 14-3-3σ, suggesting attempts to maintain supra-basal p-MDM2 and protect basal-layer p53. However, HK1.ras/fos-Δ5PTEN papillomas exhibited increasing basal-layer p-MDM2 activation that reduced p53, which coincided with malignant conversion. Despite p53 loss, 14-3-3σ expression persisted in well-differentiated squamous cell carcinomas (wdSCCs) and alongside elevated p21, limited malignant progression via inhibiting p-AKT1 expression; until 14-3-3σ/p21 loss facilitated progression to aggressive SCC exhibiting uniform p-AKT1. Analysis of TPA-promoted HK1.ras-Δ5PTEN mouse skin, demonstrated early loss of 14-3-3σ/p53/p21 in hyperplasia and papillomas, with increased p-MDM2/p-AKT1 that resulted in rapid malignant conversion and progression to poorly differentiated SCC. In 2D/3D cultures, membranous 14-3-3σ expression observed in normal HaCaT and SP1 papilloma keratinocytes was unexpectedly detected in malignant T52 SCC cells cultured in monolayers, but not invasive 3D-cells. Collectively, these data suggest 14-3-3σ/Stratifin exerts suppressive roles in papillomatogenesis via MDM2/p53-dependent mechanisms; while persistent p53-independent expression in early wdSCC may involve p21-mediated AKT1 inhibition to limit malignant progression.
PubMed: 38869281
DOI: 10.1002/mc.23771 -
Cureus May 2024Objectives To evaluate the relationship between the presence of human papillomavirus (HPV) genotypes in oral rinse samples and periodontitis. Materials and methods This...
Objectives To evaluate the relationship between the presence of human papillomavirus (HPV) genotypes in oral rinse samples and periodontitis. Materials and methods This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted in 2013-2014. The primary outcome was the periodontal status, categorized as either no periodontitis or mild periodontitis (combined) versus moderate to severe periodontitis (combined). The primary variable of interest was the presence of different HPV types in oral rinse specimens. Several confounders were selected based on previous evidence that demonstrated a potential association between HPV infectivity and periodontal disease. Results The final sample included 3103 participants. HPV genotypes 6, 35, 39, 55, 59, 71, 72, and 73 showed a statistically significant association with at least one of the periodontal statuses (p-value < 0.05). The presence of any HPV genotype was highly significantly associated with periodontal status, with a p-value of <0.001. Multivariable logistic regression analysis revealed statistically significant associations of HPV 6 and HPV 16 with periodontitis, adjusted for age, gender, diabetes, smoking, race, federal poverty level, last dental visit, and education level. Conclusion Our study highlights a potential link between periodontitis and specific HPV genotypes, such as HPV 6 and HPV 16, in oral rinse specimens. This suggests a complex interplay between periodontal disease and oral HPV infections, underscoring the need for further research to address public health concerns and inform preventive and treatment strategies. Clinical relevance Identifying a link between periodontitis and specific HPV genotypes, such as HPV 6 and HPV 16, in oral rinse samples could prompt early screening and tailored treatment approaches. This underscores the importance of oral health promotion and targeted interventions to address both conditions and improve overall patient outcomes.
PubMed: 38868258
DOI: 10.7759/cureus.60190 -
Acta Neuropathologica Communications Jun 2024Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to...
Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC. Multiomics analysis included whole-genome sequencing, whole-transcriptome sequencing, and methylation sequencing. Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP. Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP. Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination. Furthermore, methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC. Finally, the differential expression of AK1, regulated by both genomic and epigenomic factors, emerged as a potential contributing factor to the histological difference of CPP against CPC. Our results suggest pronounced genomic and epigenomic disparities between CPP and CPC, providing insights into the pathogenesis of CPT at the molecular level.
Topics: Humans; Choroid Plexus Neoplasms; Female; Male; Papilloma, Choroid Plexus; Child; Child, Preschool; Carcinoma; DNA Methylation; Infant; Adolescent; Multiomics
PubMed: 38867333
DOI: 10.1186/s40478-024-01814-y -
International Journal of Surgical... Jun 2024Bronchial papillomas are benign tumors, which can be divided into different subtypes based on the cellular features. So far, no bronchial papilloma with basaloid cell...
Bronchial papillomas are benign tumors, which can be divided into different subtypes based on the cellular features. So far, no bronchial papilloma with basaloid cell features has been reported. We report a bronchial basaloid papillary tumor in a 67-year-old woman. Tumor recurrence and malignant transformation were observed after a long-term follow-up. The clinical, histological, immunohistochemical, and genetic features were reappraised. The primary tumor was characterized by papillary growth pattern and basaloid neoplastic cells, only a small amount of neoplastic cells showed mature characteristics. The tumor originated from respiratory epithelium and had a low proliferation index by Ki-67. Keratin (KRT) 5/6 and KRT7 showed patchy or partial positivity. Myoepithelial markers were negative. P63 was diffusely positive, but it was negative in the small amount of tumor cells with mature characteristics. The common genetic alterations (, , V600E, , and ) of lung cancers were not detected. However, tumor recurrence was observed in the mediastinum and esophagus 12 years after surgery. The recurrent tumor had a morphology overlapping with that of the primary tumor; however, it displayed significantly malignant characteristics. The recurrent tumor was not related to high-risk HPV. A high variant allele frequency was observed in tumor suppressor gene , , oncogene , and , which were all missense mutations. Considering the bland features of the primary tumor and the fact of tumor recurrence and undisputed malignant transformation, the basaloid papillary tumor was considered a tumor with uncertain malignant potential.
PubMed: 38863435
DOI: 10.1177/10668969241256104 -
Current Oncology Reports Jun 2024Squamous cell carcinoma of the anus (SCCA) is an HPV-associated malignancy that has limited treatment options. Immunotherapy has expanded these options and here we... (Review)
Review
PURPOSE OF REVIEW
Squamous cell carcinoma of the anus (SCCA) is an HPV-associated malignancy that has limited treatment options. Immunotherapy has expanded these options and here we review current and emerging immunotherapeutic approaches.
RECENT FINDINGS
Multiple studies of single-agent anti-PD1/PD-L1 immunotherapy have demonstrated a modest response rate of approximately 10% to 15%. While a minority of patients (~5%) with SCCA experience durable complete responses, most advanced SCCAs are resistant to anti-PD1/PD-L1 monotherapy. Given the need for more broadly effective immunotherapies, novel strategies, such as adaptive cell therapies and therapeutic vaccination, are being explored. To reduce the recurrence risk of localized high-risk SCCA, strategies combining immunotherapy with chemoradiation are also being investigated. While a small subset of patients with SCCA have prolonged responses to PD1-directed immunotherapy, the majority do not derive clinical benefit, and new immunotherapeutic strategies are needed. Better understanding of the immune microenvironment and predictive biomarkers could accelerate therapeutic advances.
PubMed: 38861124
DOI: 10.1007/s11912-024-01564-z -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Jun 2024To explore the methods of resection, dura and skull base repair and reconstruction of cranionasal communication tumor. Data of 31 patients with cranionasal communication...
To explore the methods of resection, dura and skull base repair and reconstruction of cranionasal communication tumor. Data of 31 patients with cranionasal communication tumor who underwent dura and skull base reconstruction after tumor resection from 2018 to 2022 were collected. Follow-up lasted for 3 to 41 months. A total of 31 patients were enrolled, including 20 males and 11 females. The ages ranged from 19 to 74 years, with a median age of 57 years old. There were 17 benign lesions(one case of hemangioma, one case of Rathke cyst, one case of squamous papilloma, one case of craniopharyngioma, two cases of meningocele, two cases of varus papilloma, two cases of meningioma of grade Ⅰ, three cases of schwannoma, four cases of pituitary tumor) and 14 malignant lesions(one case of osteosarcoma, one case of poorly differentiated carcinoma, two cases of varus papilloma malignancy, two cases of olfactory neuroblastoma, two cases of adenocarcinoma, two cases of adenoid cystic carcinoma, four cases of squamous cell carcinoma) . Sixteen cases underwent nasal endoscopy combined with craniofacial incision and 15 cases underwent nasal endoscopy surgery alone. Complete resection of the mass and dura and skull base reconstruction were performed in all 31 patients, and free graft repair was performed in 8 cases(fascia lata in 5 cases and nasal mucosa in 3 cases). Twenty-three cases were repaired with pedicled flaps(septal mucosal flap alone in 11 cases, septal mucosal flap combined with free graft in 6 cases, and cap aponeurosis combined with free graft in 6 cases). Eight out of 31 patients underwent skull base bone repair. Postoperative cerebral hemorrhage occurred in 1 case, cerebrospinal fluid leakage in 1 case, intracranial infection in 2 cases. All patients were successfully treated without severe sequelae. Cerebrospinal fluid leakage and intracranial infection occurred in one patient after radiotherapy, who recovered after conservative treatment. All 17 patients with benign lesions survived. Thirteen out of 14 patients with malignant lesions received radiotherapy after surgery, nine survived without recurrence, five cases recurred, of which 2 survived with tumor, one underwent reoperation and 2 died. Cranionasal communication tumors are high-risk diseases of anterior and middle skull base, and various surgical repair methods could be selected after complete resection of the tumor. Successful reconstruction and multidisciplinary cooperation are crucial for treatment outcome.
Topics: Humans; Male; Middle Aged; Female; Adult; Plastic Surgery Procedures; Aged; Skull Base; Young Adult; Dura Mater; Skull Base Neoplasms
PubMed: 38858114
DOI: 10.13201/j.issn.2096-7993.2024.06.008