Spectrumof HPV Disease.pdf

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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

Dr David Rowen. Royal South Hants Hospital


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 – photodynamic therapy 164 intra-urethral condylomata Topical ALA followed by intra-urethral PDT through a cylindrical fibre Complete response 95% Recurrence – 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


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