Association Between β-Genus Human Papillomavirus and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals—A Meta-analysis

IMPORTANCE Existing epidemiological evidence remains controversial regarding the association between β-genus human papillomavirus (β-HPV) and cutaneous squamous cell carcinoma (cSCC) in immunocompetent individuals. OBJECTIVE We aimed to clarify this association and evaluate type-specific β-HPV involvement. DATA SOURCES We performed a systematic literature search of MEDLINE and EMBASE for studies in humans through June 18, 2014, with no restriction on publication date or language. The following search terms were used: “human papillomavirus” and “cutaneous squamous cell carcinoma or skin squamous cell carcinoma or cSCC or nonmelanoma skin neoplasms.” STUDY SELECTION Articles were independently assessed by 2 reviewers. We only included case-control or cohort studies, in immunocompetent individuals, that calculated the odds ratio (OR) for cSCC associated with overall and type-specific β-HPV. DATA EXTRACTION AND SYNTHESIS We first assessed the heterogeneity among study-specific ORs using the Q statistic and I 2 statistic. Then, we used the random-effects model to obtain the overall OR and its 95% CI for all studies as well as for each type of HPV. We also tested and corrected for publication bias by 3 funnel plot–based methods. The quality of each study was assessed with the Newcastle Ottawa Scale. MAIN OUTCOMES AND MEASURES Pooled ORs and 95% CIs for overall β-HPV and HPV types 5, 8, 15, 17, 20, 24, 36, and 38 association with skin biopsy proven cSCC. RESULTS Seventy-nine articles were assessed for eligibility; 14 studies met inclusion criteria for the meta-analysis and included 3112 adult immunocompetent study participants with cSCC and 6020 controls. For all detection methods, the overall association between β-HPV and cSCC was significant with an adjusted pooled OR (95% CI) of 1.42 (1.18-1.72). As for the type-specific analysis, types 5, 8, 15, 17, 20, 24, 36, and 38 showed a significant association with adjusted pooled ORs (95% CIs) of 1.4 (1.18-1.66), 1.39 (1.16-1.66), 1.25 (1.04-1.50), 1.34 (1.19-1.52), 1.38 (1.21-1.59), 1.26 (1.09-1.44), 1.23 (1.01-1.50), and 1.37 (1.13-1.67) respectively. Our subgroup analysis in studies using only serology for HPV detection showed a significant association between overall β-HPV and HPV subtypes 5, 8, 17, 20, 24, and 38 with an increased risk of cSCC development. CONCLUSIONS AND RELEVANCE This study serves as added evidence supporting β-HPV as a risk factor for cSCC in healthy individuals. The subgroup analysis highlights this significant association for HPV 5, 8, 17, 20, and 38, which may help to direct future prevention effort

Evaluation, diagnosis and surveillance of renal masses in the setting of VHL disease

This brief report focuses on the evaluation and diagnosis of clinically localized renal masses in children and adults with Von Hippel–Lindau (VHL) disease. Counseling considerations pertinent to the urologists, medical oncologists, and multidisciplinary teams involved in the care of these patients are addressed. As practice patterns regarding the evaluation and management of VHL tumors can vary considerably, this report aims to provide guidance on some of the controversies associated with the diagnostic evaluation and initial management of localized renal masses in VHL patients

Effective combinatorial immunotherapy for penile squamous cell carcinoma

Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Molecular mechanisms and therapies of PSCC are understudied, owing to scarcity of laboratory models. Herein, we describe a genetically engineered mouse model of PSCC, by co-deletion of Smad4 and Apc in the androgen-responsive epithelium of the penis. Mouse PSCC fosters an immunosuppressive microenvironment with myeloid-derived suppressor cells (MDSCs) as a dominant population. Preclinical trials in the model demonstrate synergistic efficacy of immune checkpoint blockade with the MDSC-diminishing drugs cabozantinib or celecoxib. A critical clinical problem of PSCC is chemoresistance to cisplatin, which is induced by Pten deficiency on the backdrop of Smad4/Apc co-deletion. Drug screen studies informed by targeted proteomics identify a few potential therapeutic strategies for PSCC. Our studies have established what we believe to be essential resources for studying PSCC biology and developing therapeutic strategies

Surgical Site Infections Following Spine Surgery: Eliminating the Controversies in the Diagnosis

Surgical site infection (SSI) following spine surgery is a dreaded complication with significant morbidity and economic burden. SSIs following spine surgery can be superficial, characterized by obvious wound drainage, or deep-seated with a healed wound. Staphylococcus aureus remains the principal causal agent. There are certain pre-operative risk factors that increase the risk of SSI, mainly diabetes, smoking, steroids, and peri-operative transfusions. Additionally, intra-operative risk factors include surgical invasiveness, type of fusion, implant use, and traditional instead of minimally invasive approach. A high level of suspicion is crucial to attaining an early definitive diagnosis and initiating appropriate management. The most common presenting symptom is back pain, usually manifesting 2 to 4 weeks and up to 3 months after a spinal procedure. Scheduling a follow-up visit between weeks 2 to 4 after surgery is therefore necessary for early detection. Inflammatory markers are important diagnostic tools, and comparing pre-operative with post-operative levels should be done when suspecting SSIs following spine surgery. Particularly, Serum Amyloid A (SAA) is a novel inflammatory marker that can expedite the diagnosis of SSIs. Magnetic resonance imaging remains the diagnostic modality of choice when suspecting a SSI following spine surgery. While 18F-fluorodeoxyglucose-positron emission tomography is not widely used, it may be useful in challenging cases. Despite their low yield, blood cultures should be collected before initiating antibiotic therapy. Samples from wound drainage should be sent for Gram stain and cultures. When there is a high clinical suspicion of SSI and in the absence of superficial wound drainage, CT guided aspiration of paraspinal collections is warranted. Unless the patient is hemodynamically compromised, antibiotics should be deferred until proper specimens for culture are secured

Complete Response of Primary Penile Tumor With Induction Paclitaxel, Ifosfamide, and Cisplatin (TIP) Chemotherapy

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Complete Response of Primary Penile Tumor With Induction Paclitaxel, Ifosfamide, and Cisplatin (TIP) Chemotherapy

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Adding Cyclooxygenase Inhibitors to Immune Checkpoint Inhibitors Did Not Improve Outcomes in Metastatic Renal Cell Carcinoma

Modulating the cyclooxygenase 2 (COX-2) pathway has improved responses to immune checkpoint inhibitors (ICIs) in certain solid tumors, such as melanoma. Little is known about COX-2 inhibition in response to ICIs in metastatic renal cell carcinoma (mRCC). In this retrospective cohort study, we examined the effect of COX-2 inhibitors on the long-term outcomes of mRCC patients undergoing ICI therapies. Among 211 patients with mRCC, 23 patients were excluded due to loss to follow-up. Among 188 included patients, 120 patients received either an NSAID or aspirin for at least three weeks during ICI therapies. Clear cell histology was present in 96% of cases. The median overall survival (OS) was similar regardless of the COX inhibitor (COXi) (i.e., NSAID or aspirin) use (27 months for COXi vs. 33 months for no-COXi groups; p = 0.73). The no-COXi group showed a trend toward longer median progression-free survival (8 months for COXi vs. 13 months for no-COXi groups; p = 0.13). When looking specifically at NSAID use in a multivariate analysis, NSAID use was associated with a higher risk of progression (HR = 1.52 [95% CI, 1.04–2.22]) and death (HR = 1.60 [95% CI, 1.02–2.52]). In summary, COXis did not improve disease control or survival among patients with mRCC who were undergoing ICI therapies. Instead, the concurrent use of NSAIDs was associated with worse outcomes. Larger studies are needed to validate our observation