Management of Genital HPV

IFCCP Jeddah Jan 2014James Bentley

Professor Dept. Obstetrics and GynecologyDalhousie University

Halifax, Canada

Introduction

• Genital warts, condyloma acuminata

– one of the most common STIs

• 90% caused by HPV 6 & 11

• Incubation: 1-8 months

• Risk factors: lifetime # of sexual partners

• Prevention:

– Vaccination

– Condoms may help

Management: Condyloma Acuminata

• Inspection, vaginal speculum examination– Bright light source , magnification may help

– Possibility of other STI : offer screening

• Cytology: Women with anogenital warts– 25% have cervical or vaginal acuminate warts

– 50% have flat lesions or CIN

• Acetic Acid: – not recommended unless colposcopy performed

• HPV typing :– Not recommended, usually associated with low risk HP virus

What to biopsyWhen Where

All cervical lesions (colposcopy) Most abnormal area

Uncertain diagnosis

Treatment failure Base and side of lesion

Large, pigmented, ulcerated,papular or macular vulvarlesions

>35y vulvar lesions With adjacent normal tissue

Immunocompromised

Clinical Presentation: Genital warts

• Asymptomatic, subclinical infection which clears spontaneously most common

• Symptoms– Itching, burning, bleeding, vaginal discharge

• Location:– posterior forchette> labia majora> labia minora

• Appearance– Multiple papillomatous growths, less frequent

papules, macules

Von Krogh G, Sex Transm Inf 2000;76:162-8Dunne E, CID 2006;43:624-9

Vulvar papillomatosis

Cervical Condyloma

Cytology

• Koilocytes with nuclear atypia and delayed maturation

Sedlacek T, Clinical Obs and Gyn 1999;42:206-20

Histology

• Koilocytes in superficial Malpigian and granular layers

• Hyperkeratosis, acanthosis, parakeratosis, dyskaryosis

Nebsio C, International J Dermatology 2001;40:373-9

Differential Diagnosis

• Normal anatomy: micropapillomatosis, sebaceous glands

• Benign conditions: seborrheic keratosis, fibroepitheloma, intradermal nevi

• Infection: Molluscum contagiosum, condylomata lata of secondary syphilis, genital herpes

• Intraepithelial neoplasia, malignancy

Papillomatosis

• Papillary projections inner surface of labia minora & introitus

• Single base vs warts fused at base

• 1% of women

Von Krogh G, Sex Transm Inf 2000;76:162-8Salvini C, CMAJ;179:799-800

Treatment Indications genital warts

• Spontaneous resolution 20-30% in 3 months

• Alleviate symptoms

• Psychological distress

• Counseling: treatment does not eliminate presence of virus, infectivity

Treatment: Patient Applied

• Podophilox: CondylineTM, WartecTM

– 0.5% solution of purified podophyllotoxin, a mitotic poison

– Apply BID x 3 days then 4 days off

– Maximum 6 weeks duration & 0.5ml/d & <10cm2/d

• Clearance rate 45-90%, Recurrence 30-60%

• Contraindication– Pregnancy: teratogenic

– Abraded skin, vagina, cervix, anus: neurotoxin

Patient-applied Therapy

• Imiquimod: AldaraTM

– Immune response modifier

– 3 times weekly at HS up to 16 weeks, at least 1 day in between applications, wash in AM

• Clearance 56%, Recurrence 10-50%

– One study found lowest recurrence rate of any treatment

• Contraindication: pregnancy

Edwards L, Arch Derm 1998;134:25-30Canadian Guidelines on STI 2008

Office Treatment

• Cryotherapy: Liquid nitrogen, carbon dioxide (Histofreeze) or nitrous oxide with cryoprobe– After freezing tissue necroses (hypopigmentation)– Apply directly 30-60s ice ball includes lesion and 1-

2mm surrounding tissue– Weekly

• Clearance 60-90%, Recurrence 40%• Safe in pregnancy• Contraindications: not in vagina

Office treatment

• Bi- or Trichloracetic acid (50-90% solution in 70% alcohol)

– Caustic, causes necrosis

– Cotton tip applicator weekly

• Clearance 70-80%, Recurrence 36%

• Advantage: cost, pregnancy, cervix, vagina

• Caution do not over apply

– ulceration into dermis; caution on mucosa

Office Treatment:• Podophyllin: preferably avoid this therapy

– Nonstandardized resin extract from Podophyllumplant in tincture of benzoin 10-25% solution

– Weekly application x4, wash off few hours later– Maximum 1-2ml/ application

• Adverse effects– Chemical burns, rare systemic toxicity ( neurological,

hematological)

• Contraindication– Pregnancy, abraded skin, mucosa

Surgery:anaesthesia, colposcopy clinic or operating theatre

CO2 Laser IR light absorbed and tissue vapourizedColposcopic guidanceBest depth control : endpoint underlying papillary dermis visiblePreserve normal anatomyViral particles in smoke plume

Loop Electrosurgical Excision Procedure

LEEP

Difficult to control depthNot in vagina

Electrofulguration More pain and potential scarring

Surgical Excision Skin grafts may be requiredLoss of normal anatomy

Treatment not recommended

• 5 Fluorouracil 5% cream, Efudex• Pyrimidine antimetabolite prevents DNA synthesis

• Topical or vaginal application; frequent ulceration

• Contraindicated in pregnancy

• Interferon intralesional• Proteins with antiviral properties, lengthen cell cycle

and increase lysis

• Flu like symptoms, pain

• Contraindicated in pregnancy

Pregnancy

• Considerations:

– Worsening lesions: relative immunosuppressionwarts proliferate or may have recurrence

– Indication for treatment: symptoms or potential obstruction of birth canal

– Choice of treatment: avoid potentially teratogenicmedical therapy

– Transmission to fetus: is Caesarian section indicated?

Genital HPV Infection in Pregnancy

• Treatment not necessary unless potentially obstructive or symptoms

• TCA most effective in 2nd half of pregnancy

– fewer recurrences, lesions stable at this time

• Laser in 3rd trimester for extensive condylomata

• Spontaneous regression or resolution postpartum

ACOG Practice Bulletin 2005;61:905-918

Recurrent Respiratory PapillomatosisRRP

• Most common benign neoplasm of larynx

• Usual cause HPV 6 & 11• Presents in childhood or

adult: hoarseness• Possible modes of

transmission to infant:– Vertical during labour and

delivery– Vertical in utero ascending

or transplacental– Direct casual contact– Sexual abuse

Kosko J, Int J Ped Otorhinolaryngol 1996;35:31-38

Papillomas

Respiratory Papillomatosis

• Mode of transmission not established

• C/S with intact membranes has been associated with RRP in child

• Treatment of condyloma during pregnancy does not eradicate latent HPV

• Caesarian section for sole indication of prevention of RRP not recommended

Kosko J, Int J Ped Otorhinolaryngol 1996;35:31-38ACOG Practice Bulletin 2005;61:905-918

Immunosuppression & HIV/ AIDS

• Extensive lesions, resistant to therapy, more recurrences

• Imiquimod 1st line therapy

• Laser: ablative, multiple biopsies

• Increased malignant transformation: BIOPSY

– Immunocompetent women 90% warts HPV 6 & 11

– Immunosuppressed up to 50% warts high risk oncogenic HPV www.utdol.com/online/content/topic.do?topicKey=gen_gyne

(accessed Apr 13, 2009)

Summary: Condyloma Acuminata

• Common– Lifetime risk HPV 70%, warts 10%

• Spontaneous resolution:– Placebo controlled trial 20-30% in 3 months

• Biopsy not required in healthy women <35y• Treatment choice

– Patient preference, provider experience, pregnancy– Combination therapy

• Latent virus – Recurrences 30%, transmission to partner