papilloma viruses: from tip to tail tim palmer
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Papilloma viruses:from tip to tail
Tim Palmer
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Taxonomic level
Criteria Number
Genera
Less than 60% nucleotide (nt) identity in entire L1 ORF
18 genera (alpha to sigma)2 additional new genera, yet unnamed (containing TtPV2 and RaPV1 respectively)
Species Between 60% and 70% nt identity in L1
From 1 species (in most genera) up to 15 species (in genus alpha)
Genotypes Between 71 and 89 % nt identity in L1
Currently 120 papillomavirus genotypes completely genomically characterized and available in Genbank (98 human: HPV; 32 non-human)
Subtypes Between 90 and 98 % identity in L1
Very rare
Variants More than 98 % identity in L1
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• Lineage C more persistent than A or B
• A and B more commonly associated with CIN3
• Lineage B - higher association with CIN3 (2.7 OR)
HPV 31
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Non-human papilloma viruses
• Bovine (6 types)• Equine• Canine• Feline• Rabbit (2 types)• Mouse• Hamster• Deer• Reindeer
• European elk• Sheep• Porpoise• Monkey (Rhesus
and chimpanzees)
• Parrots• Chaffinch• Tortoise• Manatees
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• Squamous epithelia – keratinising and non-keratinising o Cutaneous
o Genital
o Aero-digestive tract
• Papillomas
• Fibropapillomas
• ‘Sarcoids’
• Malignant transformation
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Illustration from Tableau Encylopedique and Methodique 1789
Cottontail rabbit with cutaneous papillomatosis – Shope papilloma virus (Museum Nat Hist, Kansas)
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• Evolved at the same time as reptiles
• DNA virus
• Protein coat (capsid)• Early and late genes
• E6 and E7 necessary for transformation (immortalisation)
• L1 and L2 form capsule
• L1 most conserved part of genome
• L1 capsid protein used for vaccines
Papilloma viruses
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HPV genome
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Human disease
• Cutaneous wartso Ano-genital warts
o Verruca vulgaris, plana, plantaris etc
o Epidermodysplasia verruciformis
• Mucosal wartso Cervical
o Oral
o Anal
o Laryngeal
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HPV immunisation in Scotland• September 2008
• Cervarix® immunisation starts at age 12-13 yr
• Catch-up cohorts up to age 18 (dob 1990)
• September 2010• First immunised women start screening
• September 2013• Three full years of data available from four year
cohorts of catch-up programme
• September 2015• First ‘HPV-naïve’ women start screening
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Data available for analysis
Year of birth
Total in year of birth
Number with smears Total with
smearsFull 1 or 2
dosesNone
1990 40259 3307 934 20319 24560
1991 39362 12982 2247 7017 22246
1992 37908 12853 1373 1300 15056
1993 30944 2889 360 772 4021
Total 148473 32031 4914 29408 66353
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Immunised women more likely to be screened - p <0.0001 for all cohorts
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Any immunisation associated with less HG dykaryosis – p <0.0001
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Immunisation associated with less low grade dyskaryosis – p <0.0001
Significant difference between cohorts in percent low grade dyskaryosis
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Full immunisation only associated with less borderline changes – p <0.0001
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Full immunisation only associated with less HG CIN in all cohorts – p<0.0001 Partial immunisation associated with less HG CIN in 1990 only – p<0.0001
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Full immunisation associated with less LG CIN in all cohorts – p<0.0001 Partial immunisation associated with less LG CIN in 1991-3 only – p<0.0001
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Oro-pharyngeal cancer• Explosion in last 15 years
• Tonsil, base of tongue, basaloid
• HPV 16 almost exclusively
• ? Pre-invasive phase
• >= 50% HPV driven
• non-smoker, non drinker, male > female, young > old, I >V
• Better prognosis, stage for stage
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Anal squamous carcinoma
• Used to be uncommon
• HPV driven in many cases
• HIV +ve: almost all are HPV+
• Anal canal may be reservoir for HPV in male and female
• Pre-invasive disease
• Screening
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