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Head and neck (HN) carcinomas (mostly represented by squamous cell carcinomas [SCC]) still have a poor prognosis, which could be dramatically improved with immunotherapy. Tumor's microenvironment changes, caused by many endogenous or exogenous events, can correlate with prognosis and therapeutic response. Here, we review recent data regarding HNSCC, nasopharyngeal carcinomas (NPC) and salivary gland malignant tumors, all three being potential target of immunotherapies. About half of HNSCC exhibit PD-L1 expression, this expression being upregulated in HPV-positive tumors. In recent clinical trials, a better therapeutic response to anti-PD-1 has been obtained in patients with higher PD-L1 expression. Food and Drug Administration (FDA) approved the use of these therapeutics without the screening of patients regarding PD-L1 status. Activation status, density and localisation of TIL as well as PD-L2, γ-interferon, inflammatory cytokines, epithelial-mesenchymal transition phenotype and mutational burden may all be potential therapeutic response markers. In Epstein-Barr Virus (EBV)-induced nasopharyngeal non-keratinizing cancer, PD-L1 is over-expressed compared to EBV negative-tumors. A 22 % response rate has been observed under anti-PD-1 treatment, among PD-L1-positive HNSCC patients. There is little data regarding microenvironment of salivary gland cancer. PD-L1 shows great heterogeneity in localisation, when expressed. A 11 % response rate has been obtained under anti-PD-1 treatment among PD-L1-positive NPC patients. A better understanding of immune checkpoint regulation processes needs to be achieved to allow patients with HN carcinomas to benefit from these promising immunotherapies., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Condyloma, also known as venereal warts, are caused by human papillomavirus (HPV). Conventional wart therapies destroy infected keratinocytes rather than directly inhibiting viral infection or replication. No available drug therapy effectively eliminates HPV. Treatments are often disappointing for the patient, the family and the physician due to the duration of the disease and the frequency of recurrences in spite of treatment.

Immunomodulators have been used for some time in various medical specialities, but have only recently been used in gynaecology. The first drug in this therapeutic class, Immiquimod (Aldara), has been shown to be effective in treating lesions induced by Human Papillomavirus (HPV) such as genital warts or cervical and vulvar dysplasia, by stimulating the immune system of an infected individual. Thanks to its ease of use and its few side effects, Imiquimod would appear to be, in the future, the treatment of choice for these types of viral infections, alone or in association with therapeutic vaccines or physical abative therapies as a prevention of relapses. This review aims at summarizing and clarifying the mechanism of action of the different immunomodulators, their indications and their effectiveness in gynecologic practice.

Purpose: Human Papillomaviruses (HPV) are epitheliotropic for stratified malpighian epithelia such as those of the cervix. Among them, oncogenic viruses are detectable in 99.7% of cervical cancers. A great priority is to develop a vaccine either against primary infection (preventive vaccine) allowing protection against HPV infection or therapeutic vaccine in order to kill previously infected or transformed keratinocytes., Current Knowledge and Key Points: Preventive vaccines against HPV contain virus like particles (VLP) 16 and 18 and induce a high titer of blood anti-VLP antibodies. They were recently tested in humans and have shown true efficiency for the prevention of cervical cancer. The therapeutic vaccines are therefore currently being developed in order to increase anti-HPV natural CD4+ and CD8+ T-cell immunity in women infected during their sexual activity., Future Prospects: The perspective of the prophylactic vaccines is to decrease both genital HPV infection and cervical cancer. The impact of preventive vaccine must be carefully analyzed in order to prevent collateral side effects. The therapeutic vaccines have also a future in women already infected by HPV and might have an efficiency similar to surgery in the treatment of cervical intraepithelial neoplasia.

Introduction: High risk human papillomaviruses (HPV) have emerged as risk factors for anal carcinoma particularly in HIV-infected patients who demonstrate a high rate of anal HPV infection. Considering the relationship between the presence of anal infection and the development of neoplastic lesions, we wished to assess the capacity of imiquimod to eradicate latent HPV infection in HIV-infected patients., Patients and Methods: We conducted a prospective, randomized, double-blind and vehicle controlled study. Two consecutive anal swabs were taken at 2 month intervals and only patients with two consecutive tests positive for the detection of HPV-DNA (Hybrid Capture II) were included. Patients with persistent latent HPV infection were divided into 2 groups who applied imiquimod versus vehicle during 6 weeks. HPV-DNA presence was then investigated 2 and 4 months following the onset of treatment., Results: Among the 80 HIV-infected patients, 26 (32.5 p. 100) had 2 positive consecutive assays, and 19 patients were included in the study. After randomization, 9 patients received imiquimod and 10 vehicle. There was no significant difference between treatment groups according to the following criteria: gender, route of HIV transmission, CDC stage, prior medical history of sexually transmitted diseases or anogenital warts. 33.3 p. 100 (3/9) of patients treated with imiquimod were negative at M2, whereas 100 p. 100 (10/10) vehicle treated-patients remained positive (p=0.08). Similar results were observed at the M4 visit., Discussion: Our study confirmed the increased prevalence of latent HPV-DNA infection in HIV-infected patients. In spite of the low number of treated patients, we did not observe a statistically significant decrease in HPV-DNA in anal swabs from imiquimod-treated patients as compared to placebo-treated patients.

Introduction: Cidofovir (Vistide) is an antiviral marketed for the treatment of cytomegalovirus retinitis. Clinical efficacy has been reported with its broad antiviral spectrum that includes poxvirus, human papilloma virus and Herpes simplex. In immunodepressed patients, these infectious dermatoses are often recurrent and resistant. In an open study, we assessed the efficacy and clinical tolerance of cidofovir gel at 1 p. 100., Patients and Methods: Twelve HIV-infected adults were included. Cidofovir gel at 1 p. 100 was applied directly on the lesions, once a day, for two weeks on the molluscum and condylomas, four weeks on the warts and one week on the chronic herpes., Results: Four patients presented with warts and 3 of them with verruca plana. In 2 of the verruca plana patients, regression was complete although relapse was observed. Two failures were noted. Local application of the gel was not tolerated by one patient suffering from condylomas of the penis. Four patients presented with molluscum contagiosum. Two complete regressions with strong local reaction and two partial regressions were observed. The latter two patients exhibited severe immunodepression, one of them subsequently received infusions of cidofovir. Two women suffering from vulvar and perianal herpes resistant to acyclovir were treated for one week with cidofovir gel at 1 p. 100: no response was obtained. One of the patients stopped treatment because of local intolerance. A third, less immunodepressed, woman responded partially., Comments: In HIV-positive patients, cidofovir in topical form appears to be indicated in extensive and confluent molluscum contagiosum. However, the effect occurs at the cost of local inflammation. The results are disappointing in papillomavirus lesions and in chronic acyclovir-resistant herpes ulcerations, efficacy is debatable.

Laryngeal papillomatosis, due to type 6 and 11 papova-virus A, causes devastating lesions leading to difficult clinical situations (severe dysphonia, or laryngeal dyspnea). Recurrence requires repeated endoscopy with CO2 laser treatment to keep the airways free and prevent the lesions spreading. In patients presenting aggressive papillomatosis, such repeated intervention causes irreversible lesions which have a very negative impact on the vocal prognosis. In this context, developing a form of minimally invasive surgery would help avoid vocal sequelae as far as possible. Thus, anti-viral agents can be injected directly into the lesion per-operatively so as best to preserve the healthy mucosa and muscles, thereby managing the lesions with precision and less iatrogenic impact than with CO2 laser. Twenty six patients since 1998 have undergone Cidofovir endoscopy. Total remission was achieved in eight of them (31%), after between two and eight interventions. Twenty seven (65%) showed clinically significant partial remission. Such positive results were obtained in both adults and children. Associated lesion excision was required in cases of obstructive or persistent papilloma. Intralesion Cidofovir injection thus seems to have proved highly effective in the clinical management of laryngeal papillomatosis. Combined Cidovir injection and surgical excision remains necessary in case of large or persistent papillomas. These results have lead us to indicate this procedure as primary treatment for laryngeal papillomatosis in adults and children.

Choice of antimicrobial agents and length of therapy of infections of the female genital tract and chemotherapy are presented with particular mention to their side effects. Clinical approach and antibiotic regimens of pelvic inflammatory diseases are discussed.

A 70-year-old woman treated for sarcoidosis complained of progressive cognitive impairment and gait disability. Magnetic resonance imaging of the brain revealed a nonenhancing lesion in T1-weighted imaging in the left parieto-occipital region and sarcoidosis of the central nervous system was evoked. However, she rapidly deteriorated with posterior and cerebellar extension of the lesions, suggesting of progressive multifocal leukoencephalopathy (PML). DNA of the JC virus (JCV) was detected in the cerebrospinal fluid (CSF) by a polymerase chain reaction. Despite antiviral therapy, she died nine months after the first neurological signs. This case illustrates the possible association between sarcoidosis and PML, and underlines the interest to detect the presence of JCV in the CSF when the diagnosis of neurosarcoidosis appeared uncertain.

NEW AGENTS: Among new treatments used for infectious dermatology diseases, new agents for genital herpes, valaciclovir and famciclovir, have greatly simplified therapeutic schemes. Cidofovir has also been shown to be effective against aciclovir-resistant cutaneous and mucosal herpetic lesions and for the treatment of molluscum contagiosum. NEW ADMINISTRATION ROUTES: For genital papillomavirus infections, trials using systemic or intralesional administered interferon have not provided conclusive evidence but imiquimode appears to be quite promising. Itaconazole and fluconazole are effective for onchomycoses. NEW POSSIBILITIES: Ivermectine is effective against scabies, but must be reserved for particularly severe forms. Finally, the emergence of Neisseria gonorrhoeae strains resistant to fluoroquinolones is disquieting.

A complex immuno-chemical treatment (immuno-stimulation, blockage of virus replication, interferon induction) was applied to 23 patients with warts and vegetations with various localisations. Results confirmed the treatment efficiency.

A complex immuno-chemical treatment (immuno-stimulation, blockage of virus replication, interferon induction) was applied to 23 patients with warts and vegetations with various localisations. Results confirmed the treatment efficiency.