HPV Rollout Training

1
HPV Rollout Training

• Session 1
• HPV Molecular biology epidemiology

2
HPV Infection

• Sexually transmitted
• Transmitted via skin to skin contact
• Most HPV infection is transient

3
HPV Clearance

• Approximately 70 of new infections clear
  within one year, 91 within 2 years
• Most clear in first 6 months

4
Persistent Infection

• Persists in some women
• Persistent infection lead to an increased risk of
  CIN and cervical cancer

5
Cell Proliferation

• Governed by the Cell Cycle where DNA is
  replicated and distributed equally to the
  daughter cells.
• Processes of
• DNA Synthesis (S Phase)
• Mitosis (M Phase)Two phases are separated by
  a series of gaps (G) during which RNA and protein
  are made and the cell re-organises itself.

6
The Cell Cycle
Mitosis
DNA Synthesis
7
Normal cells

• Normal cells are constrained from excessive cell
  growth by the control processes of
  differentiation and programmed cell death
  (Apoptosis)

8
Tumour Supressor Genes

• P53 and pRb are both involved in controlling cell
  replication
• Usually if cells are damaged, checkpoints are in
  place to slow down or stop the process
• Oncogenic viruses like HPV can hijack the
  cellular machinery to promote viral replication
  by interfering with TS genes

9
HPV DNA

• HPV DNA carries oncogenes that specify proteins
  which inactivate tumour suppressors which allows
  the infected cells to keep proliferating

10
Natural history of Cervical Cancer
Epithelial cell
HPV DNA
E7
E6
Integrated DNA
p53
pRb
11
Molecular targets of early HPV proteins
Early 6 binds TS p53
Early 7 binds TS pRb
12
High Risk (HR) HPV

• Present in almost all cervical cancer
• More likely to be present in higher grades of CIN
• Unlikely that HPV alone is responsible for
  development of cervical cancer
• Co-factors

13
High-risk HPV types that cause cervical cancer in
Europe
HPV type Percentage of cervical cancer cases caused by HPV type Cumulative percentage
16 58.1 58.1
18 15.7 73.8
33 4.4 78.2
31 4.0 82.2
45 2.9 85.1
35 1.6 86.7
58 1.2 87.9
56 1.0 88.9
52 0.6 89.5
39 0.2 89.7
51 0.2 89.9
68 0.3 90.2
59 0.1 90.3
Other 1.4 91.7
No type identified 8.3 100
Adapted from Smith JS et al., 2007 Int J Cancer.
121(3)621-32.
14
HPV Testing

• Various methods systems available, not all
  approved so far
• Generally detect presence of 14 HR types of HPV
• Hybridisation of target DNA signal
  amplification (Quiagen, Hologic)
• Amplification of target DNA by PCR with type 16
  18 genotyping (Abbott, Roche)
• Transcription mediated amplification detection
  of E6/E7 mRNA (GenProbe)