Human papilloma viruses (HPV) are a small group of non-enveloped viruses belonging to the Papillomaviridae family with strong similarities to polyoma viruses. The viral particles consist of a genome in the form of a circular double-stranded DNA, encompassing eight open reading frames, as well as a non-enveloped icosahedral capsid. HPV infection is considered the most common sexually transmitted disease in both sexes and is strongly implicated in the pathogenesis of different types of cancer. ‘High-risk’ mucosal HPV types, predominantly types 16, 18, 31, 33 and 35, are associated with most cervical, penile, vulvar, vaginal, anal, oropharyngeal cancers and pre-cancers. Screening for HPV is necessary for the prognosis and for determining treatment strategies for cancer. Novel HPV markers, including proteomic and genomic markers, as well as anti-papillomavirus vaccines are currently available. The aim of this comprehensive review was to thoroughly present the updated information on virus development, cancer occurrence, treatment and prevention strategies, in an attempt to shed further light into the field, including novel research avenues.

Capsaicin is a natural protoalkaloid recognized as the main pungent component in hot peppers ( Capsicum annuum L.). The capsaicin receptor is highly expressed in the unmyelinated type C nerve fibers originating from small diameter sensory neurons in dorsal root ganglia and cranial nerve ganglia correspondents. Capsaicin and related vanilloids have a variety of effects on primary sensory neurons function, from sensory neuron excitation characterized by local burning sensation and neurogenic inflammation, followed by conduction blockage accompanied by reversible ultrastructural changes of peripheral nociceptive endings (desensitization), going as far as irreversible degenerative changes (neurotoxicity). The main role in capsaicin-induced neurogenic inflammation relies on the capsaicin sensitive, small diameter primary sensory neurons, therefore its evaluation could be used as a diagnostic instrument in functional alterations of cutaneous sensory nerve fibers. Moreover, capsaicin-induced desensitization and neurotoxicity explain the analgesic/anti-nociceptive and anti-inflammatory effects of topical capsaicin and its potential use in the management of painful and inflammatory conditions. In this study, we describe the effects of capsaicin on neurogenic inflammation and nociception, as well as its potential diagnostic value and therapeutic impact in various conditions involving impairment of sensory nerve fibers.

In vivo reflectance confocal microscopy (RCM) is a modern, non-invasive imaging technique, which allows for real-time examination of the upper layers of the skin at a resolution similar to that of classic microscopy. In addition, it has the advantage of real-time evaluation of blood flow and dynamic monitoring of cutaneous changes while preserving tissue integrity. The present study reported on the in vivo RCM technique as an objective method for the noninvasive assessment of psoriasis vulgaris that is potentially applicable in clinical studies and in monitoring the evolution of lesions under treatment. In psoriasis lesions, RCM virtual horizontal sections at the level of the dermo-epidermal junction featured numerous and prominent dermal papillae that were not surrounded by bright rings of basal cells. Micromorphological examination of the lesions using this technique revealed that mean values of the section area, the perimeter and the Feret's diameter of the dermal papillae were significantly higher in psoriatic lesions than in normal skin. An increased number of capillary vessels per lesional dermal papilla as compared to healthy skin was observed. Furthermore, micromorphological parameters of dermal capillaries were increased in psoriatic skin. These observations point to the utility of in vivo RCM as a promising technique for the non-invasive diagnosis of psoriasis vulgaris, for monitoring the evolution of lesions at a micromorphological level under various treatments and for gaining a better understanding of the pathophysiological processes that occur in the evolution of this disease.

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Capsaicin is the main pungent in chili peppers, one of the most commonly used spices in the world; its analgesic and anti-inflammatory properties have been proven in various cultures for centuries. It is a lipophilic substance belonging to the class of vanilloids and an agonist of the transient receptor potential vanilloid 1 receptor. Taking into consideration the complex neuro-immune impact of capsaicin and the potential link between inflammation and carcinogenesis, the effect of capsaicin on muco-cutaneous cancer has aroused a growing interest. The aim of this review is to look over the most recent data regarding the connection between capsaicin and muco-cutaneous cancers, with emphasis on melanoma and muco-cutaneous squamous cell carcinoma.

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Non-melanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. In spite of intensive efforts aimed towards awareness campaigns and sun-protective measures, epidemiological data indicate an increase in the incidence of NMSC. This category of skin cancers has many common environmental triggers. Arising primarily on sun-exposed skin, it has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC. Aside from the well-known etiopathogenic factors, studies have indicated that several neuroactive factors are involved in the carcinogenesis of two of the most common types of NMSC, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with the exception of penile SCC, for which a paucity of specific data on their pathogenic role exists. The complex interaction between the peripheral nervous system and target cells in the skin appears to be mediated by locally released neuroendocrine factors, such as catecholamines, substance P, calcitonin gene-related peptide and somatostatin, as well as neurohormones, such as proopiomelanocortin and its derived peptides, α-melanocyte-stimulating hormone and adrenocorticotropin. All these factors have been, at least at some point, a subject of debate regarding their precise role in the pathogenesis of NMSC. There is also a significant body of evidence indicating that psychological stress is a crucial impact factor influencing the course of skin cancers, including SCC and BCC. Numerous studies have suggested that neuroendocrine factor dysregulation, as observed in stress reactions, may be involved in tumorigenesis, accelerating the development and progression, and suppressing the regression of NMSC. Further studies are required in order to elucidate the exact mechanisms through which neuroactive molecules promote or inhibit cutaneous carcinogenesis, as this could lead to the development of more sophisticated and tailored treatment protocols, as well as open new perspectives in skin cancer research.

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies. Therefore, the major goal of cancer treatment is inhibition of tumor cell growth and of metastasis development. In order to choose the best management option for HNSCC patients, we need to identify reliable prognostic factors and to develop new molecular techniques in order to obtain a better understanding of therapy resistance. By acting as neurohormones, neurotransmitters, or neuromodulators, the neuroendocrine factors are able to signal the maintenance of physiological homeostasis or progression to malignant disease. Certain neuropeptides possess strong antitumor properties acting as tumor suppressors and immunomodulators, providing additional benefits for future potential therapeutic strategies. In light of the current understanding, cancer starts as a localized disease that can be effectively treated if discovered on proper time. Unfortunately, more than often cancer cells migrate to the surrounding tissues generating distant metastases, thus making the prognosis and survival in this stage much worse. As cellular migration is mandatory for tumor invasion and metastasis development, searching for alternate controllers of these processes, such as the neuroendocrine factors, it is an active tremendous task.