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Chow LT, Broker TR, Steinberg BM. The natural history of human papillomavirus infections of the mucosal epithelia. APMIS 2010; 118: 422-449.Human papillomaviruses (HPVs), members of a very large family of small DNA viruses, cause both benign papillomas and malignant tumors. While most research on these viruses over the past 30 years has focused on their oncogenic properties in the genital tract, they also play an important role in diseases of the upper aerodigestive tract. Rapidly accelerating advances in knowledge have increased our understanding of the biology of these viruses and this knowledge, in turn, is being applied to new approaches to prevent, diagnose, and treat HPV-induced diseases. In this introductory article, we provide an overview of the structure and life cycle of the mucosal HPVs and their interactions with their target tissues and cells. Finally, we provide our thoughts about treatments for HPV-induced diseases, present and future. PART I. INTRODUCTION AND OVERVIEWHuman papillomaviruses (HPVs) are most commonly known for their benign and neoplastic diseases of the anogenital tract. These viruses are also the causative agents of laryngeal papillomas and other hyperproliferative epithelial lesions of the airway mucosa, collectively known as recurrent respiratory papillomatosis (RRP; see the article by Larson and Derkay for a detailed description of this disease). HPVs can also infect other sites in the head and neck (H&N) region such as the conjunctiva of the eyes, ear canals, nasal sinuses, and oral cavity, especially the oropharynx and tonsils. Although not as prevalent as genital tract infections, HPV infections and lesions of the airway tract are among the most difficult to investigate, to understand, to prevent, and to bring under therapeutic control.For biomedical research into papillomaviruses and their associated diseases to lead to effective public health measures, both viruses and host responses to infection must be understood in considerable molecular detail. This introductory overview considers many attributes of HPVs including some of the similarities and differences of HPV genotypes, disease manifestations and the natural history of infections as determined from analyses of patient specimens. We also describe the genetic and functional organization of the viral genome, the regulation of viral Ó 2010 The Authors Journal Compilation Ó 2010 APMIS DOI 10.1111/j. 1600-0463.2010.02625.x 422 transcription and RNA processing, the mechanisms of viral DNA replication and long-term maintenance, the properties of the viral proteins, the nature of virus-host interactions in support of viral DNA amplification, and virion morphogenesis. Then we summarize the pathogenic consequences across the spectrum of benign lesions, neoplastic progression, and ultimately cancers, and the clinical management of infections. We necessarily consider in detail the biology of the host tissue for all papillomaviruses -the epithelium.One of the most challenging aspects of HPV research has been that few, if any, ...

Abramson AL. Recurrent respiratory papillomatosis: a complex defect in immune responsiveness to human papillomavirus-6 and -11. APMIS 2010; 118: 455-470. Recurrent respiratory papillomatosis (RRP) is a rare disease of the larynx caused by infection with human papillomaviruses (HPV) -6 or -11, associated with significant morbidity and on occasion mortality. Here we summarize our current understanding of the permissive adaptive and innate responses made by patients with RRP that support chronic HPV infection and prevent immune clearance of these viruses. Furthermore, we provide new evidence of T H 2-like polarization in papillomas and blood of patients with RRP, restricted CD4 and CD8 Vb repertoires, the effect of HPV-11 early protein E6 on T-cell alloreactivity, enriched Langerhans cell presence in papillomas, and evidence that natural killer cells are dysfunctional in RRP. We review the immunogenetic mechanisms that regulate the dysfunctional responses made by patients with RRP in response to HPV infection of the upper airway. In addition, we are identifying T-cell epitopes on HPV-11 early proteins, in the context of human leukocyte antigen (HLA) class II alleles enriched in RRP that should help generate a therapeutic vaccine. Taken together, RRP is a complex, multigene disease manifesting as a tissue and HPV-specific, immune deficiency that prevents effective clearance and ⁄ or control of HPV-6 and -11 infection.