Papilloma viruses: from tip to tail Tim Palmer.

Papilloma viruses:from tip to tail

Tim Palmer

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

• 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

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

• Squamous epithelia – keratinising and non-keratinising o Cutaneous

o Genital

o Aero-digestive tract

• Papillomas

• Fibropapillomas

• ‘Sarcoids’

• Malignant transformation

Illustration from Tableau Encylopedique and Methodique 1789

Cottontail rabbit with cutaneous papillomatosis – Shope papilloma virus (Museum Nat Hist, Kansas)

• 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

HPV genome

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

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

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

Immunised women more likely to be screened - p <0.0001 for all cohorts

Any immunisation associated with less HG dykaryosis – p <0.0001

Immunisation associated with less low grade dyskaryosis – p <0.0001

Significant difference between cohorts in percent low grade dyskaryosis

Full immunisation only associated with less borderline changes – p <0.0001

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

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

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

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