Asian Pac J Cancer Prev. 2011; 12(9): 2397-400
Ozgul N, Tuncer M, Abacioglu M, Gultekin M

Background and Purpose: In order to develop cost effective health strategies regarding HPV screening and prevention methods, determining the incidence and prevalence of HPV as well as the diseases it gives rise to such as cervical cancer and genital warts is essential. This study is a first step in determining nationwide annual prevalence of genital warts in Turkey. Patients and Methods: Through the survey sent to gynecologists in each city in Turkey, a record number of data for 4,013,084 patients, out of which 5511 diagnosed with genital warts were collected from 81 cities. The survey was sent in May 2011 and recollected in July 2011. The data belonged to patients consulted in 2010. Patients ranged between women 30-65 years old. The prevalence per city was projected using population per city as presented in Turkish Statistical Institute (TUIK). The treatment types prescribed and conducted for each patient and number of referrals were also collected. Results: The annual prevalence of 154 per 100,000 women aged 30-65 was found as the Turkey average. Given 15-37% recurrence rate estimates based on distribution of treatments provided in Turkey, an annual incidence of 97-131 per 100,000 women is estimated. Wide regional differences were observed across regions, with Aegean Region having the highest and the Southern Eastern regions having the lowest annual prevalence rates in Turkey. Conclusion: The annual prevalence rates and extrapolated incidence rates are comparable to incidences in European countries where intensive research into treatment of HPV and national health strategies are developed. Turkey should deepen its research in this area. This study contributes to these efforts as a first step in determining cost effective national health strategies.

Blood. 2012 Jan 31;
Abdollahpour H, Appaswamy G, Kotlarz D, Diestelhorst J, Beier R, Schäffer AA, Gertz EM, Schambach A, Kreipe HH, Pfeifer D, Engelhardt KR, Rezaei N, Grimbacher B, Lohrmann S, Sherkat R, Klein C

We describe a novel clinical phenotype associating T- and B-cell lymphopenia, intermittent neutropenia, and atrial septal defects in three members of a consanguineous kindred. Their clinical histories included recurrent bacterial infections, viral infections, mucocutaneous candidiasis, cutaneous warts and skin abscesses. Homozygosity mapping and candidate gene sequencing revealed a homozygous premature termination mutation in the gene STK4 (serine threonine kinase 4, formerly having the symbol MST1). STK4 is the human ortholog of Drosophila Hippo, the central constituent of a highly conserved pathway controlling cell growth and apoptosis. STK4-deficient lymphocytes and neutrophils exhibit enhanced loss of mitochondrial membrane potential and increased susceptibility to apoptosis. STK4 deficiency is a novel human primary immunodeficiency syndrome.

Am J Clin Dermatol. 2012 Apr 1; 13(2): 73-96
Dall'oglio F, D'Amico V, Nasca MR, Micali G

Cutaneous warts are common skin lesions caused by human papillomavirus infection. Treatment is aimed at relieving the patient's physical and psychological discomfort and at preventing the spread of infection by autoinoculation. Among the available medical and destructive therapeutic options for cutaneous warts, none is uniformly effective or virucidal. Moreover, in most cases their safety and efficacy has not been assessed in double-blind, controlled clinical trials, so that the reproducibility of many of the listed treatments is difficult to evaluate and a possible placebo effect cannot be ruled out. The aim of this article is to describe the outcome of current therapies for each clinical wart type according to evidence-based medicine studies published in the literature. For each clinical form, the existing treatments are classified as first-, second-, and third-line therapy. First-line therapy includes medical treatments (salicylic acid, silver nitrate, glutaraldehyde) that are useful to treat a single wart or a few and/or small common warts of short duration (less than 1 year). If these treatments have failed or are contraindicated, cryotherapy may be considered as second-line therapy. For recurrent or difficult-to-treat lesions, third-line therapy includes a variety of alternative therapeutic options (topical, intralesional, systemic, and physical destruction) that are generally off-label (not US FDA approved), and whose use is limited by drawbacks or adverse effects. From pooled evidence-based medicine data, it is possible to conclude that significantly higher remission rates may be expected only with cryotherapy and salicylic acid used in combination.

Value Health. 2012 Jan; 15(1 Suppl): S29-34
Termrungruanglert W, Havanond P, Khemapech N, Lertmaharit S, Pongpanich S, Khorprasert C, Taneepanichskul S

Approximately 80% of cervical cancer cases occur in developing countries. In Thailand, cervical cancer has been the leading cancer in females, with an incidence of 24.7 cases per 100,000 individuals per year.We constructed a decision model to simulate the lifetime economic impact for women in the context of human papillomavirus (HPV) infection prevention. HPV-related diseases were of interest: cervical cancer, cervical intraepithelial neoplasia, and genital warts. The two strategies used were 1) current practice and 2) prophylactic quadrivalent vaccine against HPV types 6, 11, 16, and 18.We developed a Markov simulation model to evaluate the incremental cost-effectiveness ratio of prophylactic HPV vaccine. Women transition through a model either healthy or developing HPV or its related diseases, or die from cervical cancer or from other causes according to transitional probabilities under the Thai health-care context. Costs from a provider perspective were obtained from King Chulalongkorn Memorial Hospital. Costs and benefits were discounted at 3% annually.Compared with no prophylactic HPV vaccine, the incremental cost-effectiveness ratio was 160,649.50 baht per quality-adjusted life-year. The mortality rate was reduced by 54.8%. The incidence of cervical cancer, cervical intraepithelial neoplasia grade 1, cervical intraepithelial neoplasia grade 2/3, and genital warts was reduced by up to 55.1%.Compared with commonly accepted standard thresholds recommended by the World Health Organization Commission on Macroeconomics and Health, the nationwide coverage of HPV vaccination in girls is likely to be cost-effective in Thailand.

Dev Cell. 2012 Jan 24;
Yue T, Tian A, Jiang J

The Hippo (Hpo) signaling pathway controls tissue growth and organ size in species ranging from Drosophila to mammals and is deregulated in a wide range of human cancers. The core pathway consists of the Hpo/Warts (Wts) kinase cassette that phosphorylates and inactivates the transcriptional coactivator Yorkie (Yki). Here, we report that Echinoid (Ed), an immunoglobulin domain-containing cell adhesion molecule, acts as an upstream regulator of the Hpo pathway. Loss of Ed compromises Yki phosphorylation, resulting in elevated Yki activity that increases Hpo target gene expression and drives tissue overgrowth. Ed physically interacts with and stabilizes the Hpo-binding partner Salvador (Sav) at adherens junctions. Ed/Sav interaction is promoted by cell-cell contact and requires dimerization of Ed cytoplasmic domain. Overexpression of Sav or dimerized Ed cytoplasmic domain suppressed loss-of-Ed phenotypes. We propose that Ed may link cell-cell contact to Hpo signaling through binding and stabilizing Sav, thus modulating the Hpo kinase activity.

J Cutan Aesthet Surg. 2011 Sep; 4(3): 188-91
Soni P, Khandelwal K, Aara N, Ghiya BC, Mehta RD, Bumb RA

Intralesional bleomycin gained increasing popularity in the recent past for treatment of warts particularly in palmo-plantar and periungual regions as other modalities are not very effective. Hence we evaluated the role of intralesional bleomycin in periungual and palmo-plantar warts to know its efficacy in Indian patients.This was a placebo-controlled study.Fifty patients of multiple palmo-plantar and periungual warts were included in this study and categorized in groups A and B of 25 each. Alternate patients were included in groups A and B and treated respectively with intralesional bleomycin (1 mg/mL solution) and normal saline as placebo, fortnightly for maximum up to two injections. Patients were followed up weekly for 1 month, fortnightly up to 12 weeks, and then quarterly for 1 year. If warts persisted after 12 weeks of starting treatment, it was considered a failure. Statistical analysis was done by the chi-square test using M-stat software.Group A and B patients were having 85 warts and 72 warts, respectively. The cure rate in group A and B patients was 96.47% (82/85 warts) and 11.11% (8/72 warts), respectively, after one or two injections within 12 weeks. The difference in the cure rate between two groups was statistically highly significant (<0.0001). In group A patients, a haemorrhagic eschar was formed which gradually healed in 8-12 weeks without atrophy or pigmentation; this phenomenon was not seen in group B. Only moderate pain was observed by most of the patients during injection in both groups.The intralesional injection of bleomycin is highly effective, safe, and non-toxic in periungual and palmo-plantar warts.

Transbound Emerg Dis. 2012 Jan 25;
da Silva MA, Carvalho CC, Coutinho LC, Reis MC, de Aragão Batista MV, de Castro RS, Dos Anjos FB, de Freitas AC

The diversity of papillomavirus (PV) found in bovine cutaneous warts from Brazilian cattle was evaluated using the PCR technique with the utilization of consensus primers MY09/11 and by PCR using Bovine Papillomavirus (BPV) type-specific primers followed by sequencing. Eleven cutaneous warts from 6 cattle herds were selected. Six warts were positive for the presence of PV. The presence of BPV types 1, 2, 3, 6 and feline sarcoid-associated PV (FeSarPV) in cutaneous wart lesions, as well as the presence of co-infections, was found. To the best of our knowledge, this is the first time that FeSarPV is described co-infecting a cutaneous wart in Brazil. The present study confirms the previous finding of FeSarPV infecting cattle. These results show the necessity of more studies to investigate the diversity of PV in cattle, its diversity and the possibility of co-infection in cattle and other animals.

Rev Bras Ginecol Obstet. 2011 Nov; 33(11): 328-33
Piazzetta RC, Carvalho NS, Andrade RP, Piazzetta G, Piazzetta SR, Carneiro R

to determine the prevalence of Chlamydia and gonorrhea in a sample of women from Curitiba.this was a cross-sectional study with a sample of sexually active non-pregnant women aged between 16 and 23 years-old, with an intact uterus, with up to four sexual partners, without evidence of fever or purulent cervicitis, submitted to pelvic examination and PCR-based urine- testing for Chlamydia and gonorrhea. Exclusion criteria included: vaccination for HPV, vaccination history for the past 21 days, previous abnormal cytology, history of genital warts, splenectomy, immune disorders, and use of immunosuppressive drugs. An interview regarding sociodemographic and obstetric data and gynecological risk behavior for sexual transmitted diseases was applied. For statistical analysis, we used the c2 or Fisher’s exact test to assess the association between variables.the prevalence of Chlamydia and gonorrhea infection in the study group was 10.7 and 1.5%, respectively, and the rate of coinfection was 0.9%. No correlation was found between the age range of the volunteers, the onset of sexual activity, the number of sexual partners and of new sexual partners in the last six months, and the presence of Chlamydia or gonorrhea. In women who had vaginal discharge or ectropion, the prevalence of Chlamydia infection was two times higher than in those without such signs.the results of this study were similar to national studies using PCR in urine samples for the detection of Chlamydia and gonorrhea in samples of non-pregnant women of the same age groups and with the same background. Since the volunteers with more than four sexual partners and those who had purulent endocervicitis were excluded, it is believed that the prevalence of Chlamydia and gonorrhea infection could have been greater in this population.

J Infect Dis. 2012 Jan 19;
Cohen JI, Davila W, Ali MA, Turk SP, Cowen EW, Freeman AF, Wang K

Molluscum contagiosum virus (MCV) is a poxvirus that causes localized papules in healthy persons. We evaluated a woman with severe immunodeficiency and disseminated MCV. During treatment with CMX-001, an antiviral with activity against other poxviruses, MCV DNA was detected in 20% of plasma samples. When the patient was not receiving CMX-001, MCV DNA was detected in 50% of samples. We also noted improvement in warts on her fingers during CMX-001 therapy. Although MCV is caused by direct inoculation of virus into skin in healthy persons, in a severely immunocompromised person MCV DNA was present in blood and may spread by viremia.

Cell Oncol (Dordr). 2012 Jan 20;
Ganguly N

BACKGROUND: Human papillomavirus (HPV) is a non-enveloped, double-stranded DNA virus. HPV infection occurs through sexual route, and the virus infects mucosal and cutaneous epithelial cells. Inside the cell, the viral DNA replicates extrachromosomally. HPV is the major cause of cervical cancer worldwide. HPVs infecting mucosal epithelial cells are sub-grouped into low-risk or high-risk by virtue of them causing benign warts or cancer, respectively. The early oncoproteins of HPV, namely E4, E5, E6 and E7, are known to contribute to tumorigenesis. The roles and functions of HPV E6 and E7 have been thoroughly studied over the years. However, limited studies have been done on E5 regarding its intracellular functions. CONCLUSIONS: This review attempts to discuss the positive role of HPV16 E5 in the form of therapeutic target for cervical cancer, as well as its role in modulation of several intracellular signalling pathways leading to transformed phenotype of the host cell.

Sex Transm Infect. 2012 Jan 17;
Johnson AM, Mercer CH, Beddows S, de Silva N, Desai S, Howell-Jones R, Carder C, Sonnenberg P, Fenton KA, Lowndes C, Soldan K

ObjectivesPersistent infection with high-risk sexually transmitted human papillomaviruses (HR-HPVs) can lead to development of cervical and other cancers, while low-risk types (low-risk HPV) may cause genital warts. We explored the epidemiology of different HPV types in men and women and their association with demographic and behavioural variables.MethodsWe analysed data collected for the British National Survey of Sexual Attitudes and Lifestyles, a cross-sectional survey undertaken in 1999-2001. Half of all sexually experienced male and female respondents aged 18-44 years were invited to provide a urine sample. We tested 3123 stored urine samples using an in-house Luminex-based HPV genotyping system.ResultsHPV DNA was detected in 29.0% (95% CI 26.7% to 31.3%) of samples from women and 17.4% (95% CI 15.1% to 19.8%) from men. Any of 13 HR-HPV types was detected in 15.9% (95% CI 14.1% to 17.8%) of women and 9.6% (95% CI 8.0% to 11.6%) of men. HPV types 16/18 were found in 5.5% (95% CI 4.5% to 6.8%) of women and 3.0% (95% CI 2.1% to 4.3%) of men; and types 6/11 in 4.7% (95% CI 1.8% to 5.9%) of women and 2.2% (95% CI 1.5% to 3.1%) of men. In multivariate analysis, HR-HPV was associated with new partner numbers, in women with younger age, single status and partner concurrency, and in men with number of partners without using condom(s) and age at first intercourse.ConclusionsHPV DNA was detectable in urine of a high proportion of the sexually active British population. In both genders, HR-HPV was strongly associated with risky sexual behaviour. The minority of HPV infections were of vaccine types. It is important to monitor HPV prevalence and type distribution following the introduction of vaccination of girls.

Biochem Soc Trans. 2012 Feb 1; 40(1): 124-8
Hergovich A

The Hippo signal transduction cascade controls cell growth, proliferation and death, all of which are frequently deregulated in tumour cells. Since initial studies in Drosophila melanogaster were instrumental in defining Hippo signalling, the machinery was named after the central Ste20-like kinase Hippo. Moreover, given that loss of Hippo signalling components Hippo, Warts, and Mats resulted in uncontrolled tissue overgrowth, Hippo signalling was defined as a tumour-suppressor cascade. Significantly, all of the core factors of Hippo signalling have mammalian orthologues that functionally compensate for loss of their counterparts in Drosophila. Furthermore, studies in Drosophila and mammalian cell systems showed that Hippo signalling represents a kinase cascade that is tightly regulated by PPIs (protein-protein interactions). Several Hippo signalling molecules contain SARAH (Salvador/RASSF1A/Hippo) domains that mediate specific PPIs, thereby influencing the activities of MST1/2 (mammalian Ste20-like serine/threonine kinase 1/2) kinases, the human Hippo orthologues. Moreover, WW domains are present in several Hippo factors, and these domains also serve as interaction surfaces for regulatory PPIs in Hippo signalling. Finally, the kinase activities of LATS1/2 (large tumour-suppressor kinase 1/2), the human counterparts of Warts, are controlled by binding to hMOB1 (human Mps one binder protein 1), the human Mats. Therefore Hippo signalling is regulated by PPIs on several levels. In the present paper, I review the current understanding of how these regulatory PPIs are regulated and contribute to the functionality of Hippo signalling.