HIV AND VULVAL DISEASE

1. HIV AND VULVAL DISEASE BRUCE HOWARD SASGO November 2008

2. INTRODUCTION • HIV and AIDS pandemic marked impact on Obstetrics + Gynaecology • Marked effect on : • Spectrum of diseases • Clinical presentation • Clinical course • Approach to management

3. INTRODUCTION • SPECTRUM OF DISEASES CHANGED • HIV related infections leading cause of maternal mortality • Severe puerperal sepsis • PID requiring surgical intervention • TB of the genital tract • Kaposi’s sarcoma vulva

4. INTRODUCTION • CLINICAL PRESENTATION + COURSE • Younger age of presentation • Less obvious clinical signs due to immunosupression • More aggressive disease with rapid progression • Specifically cancers such as Ca cervix , Ca vulva , Germ cell ovarian tumours

5. VULVAL DISEASE • Significant morbidity in women • Physical , psychological , sexual • Diagnosis + treatment difficult • Protracted course with high recurrence rates • Risk of progression to cancer • Long term follow up necessary • Move towards specialised vulval clinics

6. VULVAL CLINIC • GSH Specialised Vulval Clinic • Recent Audit of 218 women over 12 yr’s ( 1987 –1999 ) • Lichen Sclerosus et A 59 ( 27% ) • Vulval warts 33 ( 15% ) • VIN 31 ( 14% ) • VIN + Cancer 25 ( 12% ) • Cancer without VIN 15 ( 7% ) • Other 55 ( 25 % )

7. VULVAL CLINIC • Changing trends in HPV related diseases • Warts , VIN , Ca vulva • Younger women • More widespread lesions • Higher recurrence rates • Large proportion HIV positive • Is the HIV pandemic changing the face of vulval disease ?

8. HPV AND HIV • Both sexually transmitted • Epidemiology same – young sexually active women • HIV is NB risk factor for HPV infection • In HIV + women : • HPV increased 2 – 3 X in cervicovaginal lavage • HPV increased 15 X in anal swabs

9. HPV AND HIV • HIV positive women increased : • Persistent shedding HPV • Number of subtypes HPV • Oncogenic subtypes HPV • Multicentric lesions • SIL lesions of cervix • Intra - epithelial ano – genital lesions • Condylomata accuminata

10. HPV \ HIV interaction • Immune suppression • Viral - viral interactions : • HPV and HIV affect different cells • HPV - squamous epithelial cells • HIV - CD4 T cells, macrophages etc • Is there evidence of molecular interaction ?

11. HPV \ HIV interaction • Clarke et al , J Clin Pathol Feb 2002 • Two pathways of tumourgenesis • Loss of Heterozygosity (LOH ) - loss of tumour suppressor genes • Microsattelite Instability ( MSI ) - inability to repair errors in replication • HIV pos cancers progress thro’ MSI • HIV neg cancers progress thro’ LOH

12. HPV \ HIV interaction • Interaction via viral proteins • HIV proteins ( eg tat , rev ,vpr ) enhancing effect of HPV proteins • Contributing to cell cycle disruption • Combined with decreased cellular and humoral immunity this leads to HPV infection and progression

13. Condylomata Accuminata • Incidence increased in HIV + women • Chiasson et al Obstet Gynecol 1997 • 396 HIV + and 375 HIV neg • Increased in HIV + ( OR 7,3 ) • Increased even when controlled for HPV • More likely to be multi-centric involving vulva , vagina and cervix

14. Condylomata Accuminata • HIV positive patients : • Treatment more difficult due to size and multicentricity • Infection rates post treatment increased • Recurrence rates increased • Increased incidence in pregnancy with rapid increase in size

15. Condylomata Accuminata • Small series at GSH 2005 : • 16 women with large warts requiring surgery ( laser + \ -- excision ) • CD4 < 200 in 7 of 11 tested • 4 recurrences requiring surgery in 1 year • Recurred at 1 , 4 , 5 , 10 months • HIV assoc warts major impact on our gynae lists. • Role of Radiotherapy

16. Vulval Intraepithelial Neoplasia • VIN may mimic many vulval disorders • Significant symptoms ( pruritis 60% ) but asymptomatic in up to 20% • Multicentric or confluent areas • White , red , brown , ulcerated or warty • Treatment : WLE , vulvectomy , laser , medical , conservative • Site , extent , depth of invasion , age , medical status including HIV

17. VIN and HPV • VIN commonly preceded by warts • VIN assoc. with SIL in 20 – 50 % • Histological changes assoc. with HPV (50 – 90 %) • 78% ( Herod et al – BJOG 1996 ) • 59% ( Shafi et al – BJOG 1989 ) • 73% ( Herod et al – BJOG 1997 ) • 65% ( GSH vulval audit – 2000 )

18. VIN and HPV • HPV changes in VIN are increasing • Herod et al ( BJOG 1996 ) • Last 5 years of audit ( ending 1992 ) • 85% of VIN had assoc. HPV changes • Median age VIN dropping : • Previously 45 , now 36 - 40 • Increase in HPV mirrors increase in VIN

19. VIN and HIV • VIN is increased in HIV + women • Probably as a result of increased HPV infection • Little was known of the natural history of vulval lesions in HIV + women • This information is important for guidelines for clinical care of these women

20. VIN and HIV • Conley et al , Lancet ( Jan 2002 ) • Prospective cohort 925 women over 7yrs • HIV + and HIV - groups • Natural history of VIN and warts • Incident findings : 6% vs 1% • Every 6 months : • Visual inspection • Cervicovaginal lavage for HPV • Colposcopy + \ - biopsy

21. VIN and HIV • Results : • Vulvovaginal lesions: 33 (9%) vs 2 (1%) RR 16,3 ( 12.9 – 20.5 ) • 28 were warts and 5 were VIN • Time to lesion : 25 mnths vs 44 mnths • Presence of HPV and low CD4 counts - significantly assoc with development of lesions

22. VIN medical management • Medical treatment may be indicated • very widespread lesions where surgery may be mutilating • Severely medically or immuno - compromised women ( HIV ) • Recurrent rates are high ( HIV ) • Many modalities used : 5-FU , Interferon , photo – dynamic therapy

23. VIN - Imiquimod • Imiquimod ( Aldara ) is an immune response modifier • Induces tissue production of Interferon and Tumour necrosis factor • Used extensively for warts • Proposed in treatment of various CA’s +VIN • Case study at GSH vulval clinic over 10 wks

24. VIN and Vulval Cancer • VIN pre-malignant role not as clear as HSIL • Most authors :5 to 10% progress to invasion • GSH audit showed 3 out of 31 ( 10% ) • Mean age VIN 40 and vulval ca 70 • Jones et al , Obstets gynecol 1994 • 7 of 8 untreated VIN while only 4 of 105 treated VIN progressed to invasion

25. Vulval Cancer • Second peak under 50 ( Jones et al 1997 ) • 77% women younger 50 were HPV + • 13% women older 50 were HPV + • Probable pathogenesis: • Younger women increased HPV • Leads to increased VIN • Increased vulval ca younger women

26. Dermatological Manefestations • Vulva is skin • Manifest with any skin lesion associated with HIV • Xeroderma • Seborrhoeic Dermatitis • Papular Pruritic Eruption • Molluscum Cotagiosum • Dermatophytosis – Tinea Corpuris/cruris • Herpes Simplex/Zoster • Syphilis/Gonorrhoea/Chlamydia/Chancroid

27. Kaposi’s Sarcoma • 15 – 25% patients with AIDS • Skin ( including vulva ) , lymph nodes , less frequently visceral organs • DD : Squamous Ca , Bacillary angiomatosis • Treatment : • HAART , Radiotherapy ,Chemotherapy if disseminated , Cryotherapy • Excision if single lesion or severely immunocompromised

28. CONCLUSION • Vulval disease has important physical , psychological and sexual implications • HIV having major impact on vulval disease • HIV increases : • incidence of HPV infection • Multicentric lesions • Number oncogenic subtypes • Persistent shedding HPV

29. CONCLUSION • HPV increases : • Condylomata accuminata • Incidence of VIN • Number of younger women with VIN • VIN increases : • Vulval cancer incidence • Younger age of onset of Ca

30. CONCLUSION • HIV is changing the face of vulval disease • Highlights the need for regular gynae and vulval examinations in HIV pos women • The increased incidence and complex nature of vulval disease justifies the establishment of specialised vulval clinics