Human papillomavirus (HPV) infections of cutaneous and genital mucosae are very common but the majority of individuals clear the infection without overt clinical disease. Those who develop lesions, also in most cases, mount an effective cell-mediated immune response and the lesions regress. The increased prevalence of HPV infections in individuals with a range of immunodeficiencies, including immunosuppression as a consequence of HIV infection, demonstrates the central importance of the CD4 T cell population in the control of established HPV infections. Failure to induce an effective immune response is related to inefficient activation of innate immunity and ineffective priming of the adaptive immune response; this defective immune response facilitates viral persistence, a key feature of high-risk HPV infection. This milieu becomes operationally HPV antigen tolerant, and the host's defences become irrevocably compromised. HPV antigen-specific effector cells are poorly recruited to the infected focus, and their activity is downregulated; neoplastic HPV-containing cervical keratinocytes expressing high levels of E6 and E7 oncoproteins are not killed in this immunosuppressive, tolerant milieu, and progression to high-grade disease and cancer can result. Highly efficacious prophylactic HPV L1 virus-like particle (VLP) vaccines circumvent viral epithelial evasion strategies since they are delivered by intramuscular injection. The stromal dendritic cells of the muscle that encounter the highly immunogenic repeat structure of the VLP then migrate with their cargo to the lymph node, initiating an immune cascade that results in a robust T cell-dependent B cell response, which generates high levels of L1-specific serum neutralizing antibodies and immune memory.

Host Responses to Infection with Human Papillomavirus

Background
Controversy exists regarding the pathogenesis of inverted papilloma as it relates to the involvement of human papillomavirus (HPV). The purpose of this report is to describe the prevalence of HPV in nondysplastic, “early inverted papilloma” and to summarize HPV detection rates in the general population and in other HPV related neoplasia.

Methods
This case series report characterizes consecutive inverted papilloma patients from January 2005 to August 2012 with regard to smoking history, dysplasia, and HPV detection rates. Presence or absence of low/high risk HPV was determined by standardized in situ hybridization DNA probes. Medline literature review was performed to determine the prevalence of HPV in inverted papilloma without moderate or severe dysplasia.

Results
Thirty-six consecutive patients were identified with an average age of 63.6 (range, 40–84) years; gender: 23 men, 13 women. More than half (55%) were active or former smokers (14% active and 41% former). High/low risk HPV was present in 1 in 36 (2.7%) patients and 1 in 36 (2.7%) had mild dysplasia. In the literature review: (1) HPV was detected in 16.4% of inverted papilloma without dysplasia; (2) oral cavity HPV detection was 4.2% to 11.4% in the normal population; and (3) HPV was normally detected in 85% to 95% of HPV-related neoplasia.

Conclusion
Given histological features of inverted papilloma and comparatively low detection rates of HPV in inverted papilloma without dysplasia (2.7%), as well as the summary of the world literature, HPV is not related to the initial pathogenesis of inverted papilloma or inverted papilloma's tendency to persist or recur. It is postulated that since inverted papilloma is more an inflammatory polyp, it is susceptible to secondary HPV infection because of its metaplasia. Tobacco and other causes of respiratory epithelium remodeling are more plausible explanations for the initial tissue transformation to inverted papilloma.

Evidence that human papillomavirus causes inverted papilloma is sparse.

Background: Head and neck squamous cell carcinomas (HNSCC) are a major health issue in many parts of the world. Recently, attention has focused on the human papilloma virus (HPV) as a potential causative agent for HNSCC. This study aimed to survey HPV occurrence in HNSCCs as part of a comprehensive molecular epidemiology approach. Methods: In this retrospective study, patients were recruited from hospitals affiliated to the Iran University of Medical Sciences, Tehran, Iran. Formalin-fixed paraffin-embedded (FFPE) blocks were subjected to DNA isolation by QIAamp® DNA FFPE Tissue Kit and nested PCR, HPV-16 specific conventional PCR, and extra INNO-LiPA HPV genotyping assays were subsequently performed. PCR products were purified with a High Pure PCR Product Purification Kit and sequenced with an ABI 3730 XL sequencer. CLC Main Workbench 5 and MEGA5 bioinformatics software was used to analyze the raw data and to create the phylogenetic tree. SPSS v.20 was applied for statistical analysis. Results: A total of 156 FFPE blocks were collected from 2011 to 2017. Total mean age (y) of participants was 60.5 ± 12.6; 77.6 % (121/156) being men and 22.4% (35/156) e women. Overall, 5/156 (3.2%) patients (3 females and 2 males) were found to be HPV positive using the three methods. HPV genotyping revealed HPV types 16, 2, 27, and 43 in these malignancies. Tumor location and lymph node involvement indicated significant differences between the sexes. Conclusion: Although high risk HPV genotypes have been associated with HNSCCs, our findings indicate a potential of low risk HPV types to also contribute to such malignancies.

http://journal.waocp.org/article_49939_4fbf428503d47234e8fcdbd40036d8b7.pdf

Human Papillomavirus Investigation in Head and Neck Squamous Cell Carcinoma: Initial Report from the Low Risk HPV Types Associations

Background: Assessment of human papillomavirus (HPV) type-specific viral load (VL) is a valid tool for determining the etiology of HPV-related skin tumors, especially when more than one HPV type is detected within one lesion. Methods: The causative HPV type was determined in 185 fresh-frozen tissue specimens of histologically confirmed common warts (CWs) collected from 121 immunocompetent patients. All tissues were tested using the type-specific quantitative real-time polymerase chain reactions (PCR) for the most common wart-associated Alpha-PV (HPV2/27/57) and Mu-PV types (HPV1/63/204). The presence of 23 additional low-risk HPVs was evaluated using a conventional wide-spectrum PCR. Results: HPV DNA was detected in 176/185 (95.1%) CWs and multiple HPV types in 71/185 (38.4%) lesions. Using the VL approach and a robust cutoff of one viral copy/cell established in this study, HPV2/27/57 were determined as causative agents in 41/53 (77.3%) and 53/71 (74.7%) CWs with single and multiple HPVs, respectively. Conclusions: CWs are mostly etiologically associated with HPV2/27/57 and only rarely with HPV1. In the majority of CWs containing multiple HPVs, a single HPV type was present in high concentration, indicating etiological association. No significant differences in VLs of lesion-causing HPV types in CWs containing single or multiple HPVs were found.

/pdf/determination-of-causative-human-papillomavirus-type-in-2aekwvnsrl.pdf

Determination of Causative Human Papillomavirus Type in Tissue Specimens of Common Warts Based on Estimated Viral Loads.

Summary

Background There have been no studies on the prevalence of types of human papillomavirus (HPV) in cutaneous warts that focus on warts in toe webs (WTW). There is no documented association between HPV 7 and WTW.



Objectives  To explore the clinical and histopathological features of WTW, and the distribution of HPV genotypes in patients with WTW.



Methods  The study group consisted of 20 patients with WTW; 31 patients with typical verruca vulgaris (VV) were enrolled as the disease control group, and 53 patients with tinea pedis and 48 healthy volunteers were enrolled as the disease-negative control group. Tissue specimens were analysed for clinical and histological features and distribution of HPV genotypes. Polymerase chain reaction (PCR)-based direct sequencing, TA cloning and type-specific PCR (TS-PCR) were performed in the WTW and VV groups. Interdigital scale specimens from patients with tinea pedis and from healthy volunteers were analysed for HPV DNA by nested PCR and TS-PCR (HPV 7).



Results  All the patients with WTW were male and nearly all were immunocompetent; their mean age was 41 ± 10 years. The lesions presented mainly as soft, friable and vegetating clusters. HPV 7 was the predominant genotype in WTW with a frequency of 80% (16/20). Fourteen specimens were taken for histopathological examination. The most frequent histological results (seven out of 14) revealed characteristics of HPV 7 infections such as heavily stained cells containing medium-sized keratohyaline granules and a pronounced hyperkeratosis with parakeratosis. TA cloning showed that the sequence shared 90% or more homology with the HPV genotype in direct sequencing. No HPV 7 DNA was found in the scales taken from toe webs without warts.



Conclusions  This is the first study evaluating the prevalence of HPV types in WTW and the first report of the association between HPV 7 and specific subgroups of patients with warts.

Association of human papillomavirus 7 with warts in toe webs.

Molecular epidemiological study on prevalence of human papillomaviruses in patients with common warts in Beijing area.

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Molecular epidemiological study on prevalence of human papillomaviruses in patients with common warts in Beijing area.