Long-Term Infection With a Particular Human Papillomavirus (HPV) Genotype, HPV Subtype, or HPV Genomic Variant Does not Significantly Influence the Clinical Course of Recurrent Respiratory Papillomatosis

Abstract

Recurrent respiratory papillomatosis (RRP) is caused by human papillomaviruses (HPV) 6 and 11, but the role of their genomic variants in the disease's clinical course is unclear. This study investigated whether long-term persistence of a particular HPV genotype, subtype or genomic variant influences the RRP clinical course. HPV genotyping was performed in paired baseline and follow-up RRP laryngeal tissue specimens of 59 patients. HPV6 and HPV11 genomic variants were determined in paired tissue specimens taken at least 10 years apart in 20 selected patients. HPV was identified in 58/59 patients, most commonly HPV6 (40/58), followed by HPV11 (17/58). The most prevalent HPV genomic variant was HPV11 A2. HPV6 A and HPV6 B1 were most frequent in aggressive RRP. In all patients, identical HPV genomic variants were identified in both paired specimens. RRP results from a long-term infection with the same HPV genomic variant that can be identified decades after disease onset. We report the longest duration of genetically confirmed persistent HPV infection in peer-reviewed literature, during a 44-year interval in a patient with HPB6 B1. This study suggests that infection with a particular HPV genotype, subtype, or genomic variant does not significantly influence the clinical course of RRP.

Keywords: HPV; genomic variant; human papillomaviruses; laryngeal papilloma; persistence; recurrent respiratory papillomatosis.

Figure 1

HPV6 genomic variants maximum likelihood phylogenetic tree. Represented are the HPV6 nucleotide sequences newly generated in this study (n = 12; marked with pink color) and context reference nucleotide sequences (n = 22). HPV6 genomic variant lineage A is colored red, sublineage B1 yellow, B2 bright green, B3 dark green, B4 bright blue, and B5 purple. The tree was rooted at the branch with lineage A. Node sizes are proportional to phylogenetic node UFBoot support (0–100), nodes receiving UFBoot scores > 70 are shown in green.

Figure 2

HPV11 genomic variants maximum likelihood phylogenetic tree. Represented are the HPV11 nucleotide sequences newly generated in this study (n = 8; marked in pink color) and context reference nucleotide sequences (n = 11). HPV11 genomic variant lineage B is colored dark blue, sublineage A1 red, A2 yellow, A3 green and A4 bright blue. The tree was rooted at the branch with lineage B. Node sizes are proportional to phylogenetic node UFBoot support (0–100), nodes receiving UFBoot scores > 70 are shown in green.