HPV – Spectrum of Clinical Disease
Dr David Rowen. Royal South Hants Hospital
Anal cancer
Cervical cancer
Head and neck cancer Farrah Fawcett 1947 - 2009
Jade Goody 1981-2009 Michael Douglas 1944 - present Dr David Rowen. Royal South Hants Hospital
Dr David Rowen. Royal South Hants Hospital
What is HPV?
Small DNA virus Only infects squamous epithelia Common virus with >125 types identified 30–40 infect the genital area 2 groups – low risk types causing warts HPV 6,11 high risk types causing cancer HPV 16,18
Dr David Rowen. Royal South Hants Hospital
Factors Determining Manifestation of HPV Disease HPV Type Anatomical Site Immune Status
Dr David Rowen. Royal South Hants Hospital
Benign Mucosal HPV-Associated Disease • Condylomata acuminata • Single • Recurrent • Chronic • Oro-pharyngeal /Upper respiratory papillomas • Single episode • Recurrent respiratory papillomatosis (RRP) • Chronic
Dr David Rowen. Royal South Hants Hospital
Neoplastic HPV-Associated Anogenital Disease • Cervical cancer • Anal cancer • Vulval cancer • Penile cancer • Vaginal cancer • Head and Neck Sq.Cell Ca. Dr David Rowen. Royal South Hants Hospital
Statistics For Genital HPV Infection UK 2010 > 95,000 new cases of genital warts diagnosed USA estimated 1-2 million cases of genital warts Current carriage 10-20% of sexually active population Life time carriage 60-80% of sexually active population
Dr David Rowen. Royal South Hants Hospital
Identification of HPV Induced Lesions/Infection Clinical lesion
- Examination
Subclinical lesion - Colposcopy/ Histology/ HPV detection
Latent infection
- Molecular biology techniques
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Natural History of Genital Warts Spontaneous regression in 20-30% at 3 months Progression approximately 50% at 3 months Chronic persistence/recurrence 20%
Dr David Rowen. Royal South Hants Hospital
Persistence of HPV infection on cervical cytology Ho et al
Woodman et al
No of patients
608
1075
Average age
20+3
18+1
FU median duration
36 mth
36 mth
Median duration of HPV infection
8(7-10) mth
14(8-15) mth Dr David Rowen. Royal South Hants Hospital
Immune responses to HPV ď‚— In progressing warts - no inflammation, no cellular infiltrate, the lesions are expressing high levels of protein in the apparent absence of an immune response. In regressing warts - infiltration of lymphocytes and macrophages - CD4 cells dominate: appearances consistent with a delayed type hypersensitivity - DTH - response - synthesis by the wart keratinocytes of bioactive ll-12
Dr David Rowen. Royal South Hants Hospital
Problems for treatment of HPV infection of genitalia Broad range of manifestations of infection Lack of effective immunological response Wart virus not responsive to current antivirals Current therapies are inadequate
Dr David Rowen. Royal South Hants Hospital
Problems for Antiviral Treatment of HPV
Kinase, polymerase and protease enzymes not encoded for by HPV
Dr David Rowen. Royal South Hants Hospital
Overview of clearance and recurrence rates in the published literature with different treatments for external genital warts (1) Clearance rates (%) Treatment
End of treatment
Recurrence rates (%)
Podophyllin
32-79
11-65
Podophyllotoxin
42-88
10-91
TCA
50-81
Imiquimod
50-62
36 13-19
Interferon Intralesional
19-62
0-33
Systemic
7-51
0-23
Topical
6-90
6 Dr David Rowen. Royal South Hants Hospital
Overview of clearance and recurrence rates in the published literature with different treatments for external genital warts (2) Clearance rates (%)
Treatment
End of treatment
Recurrence rates (%)
Cryotherapy
63-88
0-39
89-93
0-29
93-94
24
Laser therapy
27-89
<7-45
LEEP
<90
-
Surgical/scissor excision Electrocautery/ electrotherapy
Dr David Rowen. Royal South Hants Hospital
Factors possibly predicting outcome for treatment of AGW
Number of lesions Volume of lesions Morphology of lesions Anatomical site Immune status Use of treatment protocols Dr David Rowen. Royal South Hants Hospital
Future Treatment Options
New therapies New combinations Vaccines Dr David Rowen. Royal South Hants Hospital
Potential interventions against HPV Block attachment Chemotherapy
Immunomodulation Inhibitors Other receptors Vaccination - preventive - therapeutic Dr David Rowen. Royal South Hants Hospital
5% Imiquimod suppository following surgery for anogenital condyloma 10 male patients treated 3 times weekly 3-4 mth
Follow up 6-18 months
No recurrences
Kaspari, M. Br J of Derm 2002; 147: 757-9 Dr David Rowen. Royal South Hants Hospital
Randomised double blind placebo controlled study of Polyphenon E in treatment of genital warts 272 patients
30 European centres P-E
Complete Clearance
Placebo
61% Male
37%
58% Female *Adjuvant thought to have antiviral activity
Ointment better than cream Dr David Rowen. Royal South Hants Hospital
Urethral warts treated with 5aminolaevulinic acid â&#x20AC;&#x201C; photodynamic therapy 164 intra-urethral condylomata Topical ALA followed by intra-urethral PDT through a cylindrical fibre Complete response 95% Recurrence â&#x20AC;&#x201C; 5% after 6-24 months
Wang XL, Br J Dermatol, 2004:151(4): 880-5 Dr David Rowen. Royal South Hants Hospital
Topical BCG for treatment of anogenital warts 10 consecutive men Weekly application for 6 weeks Further 9 weeks in non responders Total clearance 6 in 1-2 cycles Median follow up 9.2 mths (range 4-12) Partial response 1 Non responders 3 Dr David Rowen. Royal South Hants Hospital
Some questions to ponder: • Will
the vaccines work to protect against HNSCC? • Should we be vaccinating boys? • What happens if we are already infected with HPV? • Future work Dr David Rowen. Royal South Hants Hospital