Recurrent respiratory papillomatosis: a complex defect in immune responsiveness to human papillomavirus‐6 and ‐11

Abstract

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.

Induction of robust cellular immunity against HPV6 and HPV11 in mice by DNA vaccine encoding for E6/E7 antigen

“…25 Increasing studies have revealed the association of the two subtypes with various forms of otolaryngologic diseases, including genital warts, recurrent respiratory papillomatosis, lung carcinoma, tonsillar carcinoma, laryngeal carcinoma and other malignant transformations of otherwise benign neoplasms and dysplasia of the head and neck. [3][4][5]26,27 Such etiological observations have brought HPV6 and HPV11 to greater significance in terms of clinical relevance and scientific research. The findings of this study shed light and future promise in the use of consensus sequence DNA vaccines against HPV6 and HPV11.…”

“…carcinomas of the lung, tonsil and larynx. 4 Though only found in a small percentage of cervical cancer cases, HPV6 and HPV11 have been found in 2.6-5.2% of all cases of low-grade cervical lesions.…”

“…3 Furthermore, various studies have revealed the presence of HPV6 and HPV11 in most incidences of recurrent respiratory papillomatosis. [3][4][5] Moreover, additional studies have found that HPV6 and HPV11 are associated with more aggressive forms of cancer, including Due to the strong relationship between the human papillomavirus (HpV) "high-risk" subtypes and cervical cancers, most HpV-related studies have been focusing on the "high-risk" HpV subtypes 16 and 18. However, it has been suggested that the "low-risk" subtypes of HpV, HpV6 and HpV11, are the major cause of recurrent respiratory papillomatosis and genital warts.…”

Human Papillomavirus in Non-Oropharyngeal Head and Neck Cancers: A Systematic Literature Review

“…The association of HPV6/11 with laryngeal papillomas is well-established [105]. On the other hand, very few studies have examined the rate of HPV detection in other benign laryngeal lesions.…”

Human Papillomavirus and Related Diseases - From Bench to Bedside - A Clinical Perspective

“…Together, these cells form a cycle of inhibitory immunocytes that block the function of the effector helper type I CD4-positive Tcells (TH1-like). As a result, HPV infection is not cleared, and papillomas will recur (Bonagura et al, 2010). A correlation between the severity of laryngeal papillomas and an increase of CD83-positive dendritic cells exists, and this enhancement may be due to an impaired migration of matured DC (Kovalenko et al, 2009).…”