Background
The role of HPV in cutaneous squamous cell carcinoma (cuSCC) is not well defined, with past studies showing conflicting results.
Objective
We sought to determine if there is a significant association between HPV and cuSCC and whether cuSCC from immunosuppressed patients are more likely to carry HPV than cuSCC from immunocompetent patients.
Methods
We performed a systematic review and abstracted data from articles that included: skin samples by biopsy, HPV detection by PCR, and a minimum of 10 cases and 10 controls. Pooled effect size and 95% confidence intervals were calculated using random effects meta-analysis using the inverse variance method.
Results
cuSCC were more likely to carry HPV than normal skin (pooled ES 3.43, 95% CI 1.97–5.98, p<0.0001) in all patients. An increase in HPV prevalence was found in tumors from immunosuppressed patients compared to immunocompetent patients (pooled ES 3.01, 95%CI 2.00–4.52, p<0.0001).
Limitations
The greatest limitation is the heterogeneity of the studies included. The association of higher HPV prevalence in SCC compared to normal skin does not imply causality.
Conclusion
These results contribute to evidence that HPV is associated with cuSCC. Higher HPV burden in tumors from immunosuppressed patients compared to immunocompetent patients may have therapeutic implications.
Background
The role of human papillomavirus (HPV) in the induction and maintenance of cervical, anogenital, and some oropharyngeal carcinomas is well recognized. However, its role in cutaneous squamous cell carcinoma (SCC) remains to be elucidated. HPV is thought to act as a possible co-carcinogen in the development of SCC.
Objective
To review the literature assessing the correlation and possible causation of HPV and cutaneous SCC in the immunocompetent and immunocompromised populations.
Methods
We reviewed HPV sampling and detection methods, epidemiologic studies examining HPV carriage in immunocompetent and immunosuppressed individuals, and evidence asserting an association between HPV and cutaneous SCC.
Results
Although an abundant body of evidence points toward a link between HPV and cutaneous SCC, many studies indicate otherwise. Recent studies have focused on viral activity in addition to DNA presence.
Conclusion
The possibility exists that HPV may play a role in the induction but not maintenance of cutaneous SCC.
The fungal pathogens Fusarium solani and Fusarium oxysporum cause severe corneal disease in the United States and worldwide and were the causative organisms in a recent outbreak of contact lens-associated keratitis. To characterize innate immunity in Fusarium keratitis, we developed a murine model in which conidia are injected into the corneal stroma. Immunocompetent C57BL/6 mice rapidly developed severe corneal opacification associated with neutrophil infiltration and clearance of Fusarium hyphae. In contrast, neutrophil infiltration was delayed in MyD88−/− mice, resulting in uncontrolled growth of Fusarium hyphae in the corneal stroma and anterior chamber, and eventually resulting in corneal perforation. Corneal opacification scores in TLR2−/−, TLR4−/−, and TLR2/4−/− mice were similar to those of C57BL/6 mice; however, TLR4−/− and TLR2/4−/− mice had impaired antifungal responses. The phenotype of infected IL-1R1−/− mice was similar to that of MyD88−/− mice, with uncontrolled fungal growth resulting in corneal perforation. IL-1R1−/− mice also produced significantly less CXCL1/KC in the corneal stroma compared with C57BL/6 mice consistent with delayed neutrophil recruitment to the corneal stroma. Together, these findings indicate that IL-1R1 and MyD88 regulate CXC chemokine production and neutrophil recruitment to the cornea, and that TLR4 has an important role in controlling growth and replication of these pathogenic fungi.
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