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hpv

human papilloma virus (HPV)

Introduction:

  • over 150 types but 15 are high risk types for inducing neoplasia / cancer / tumours in humans (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), 3 as probable high-risk (26, 53, and 66) and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108).
  • types 1-4 & 7:
    • found almost exclusively in skin warts in adolescents & adults
    • types 1-3 may cause anogenital warts in children
  • ano-genital types mainly include types, 6, 11, 16, 18 and 31
  • transmission:
    • direct skin-to-skin contact spreads HPV most efficiently
  • blood tests do not reliably diagnose HPV infection, past or present
  • HPV infection often resolves spontaneously via immune clearance but may remain latent for many years before becoming clinical during episodes of immunocompromise
  • once one HPV infection has resolved, a person is immune to infection by the same HPV type but may be susceptible to other types
  • genital HPV infection may trigger cancers such as cervical cancer, breast cancer, oropharyngeal cancer and increases the risk of sexually acquired HIV / AIDS
  • HIM study published in 2011 which studied sequential HPV DNA status of 1159 unvaccinated adult males in Florida with median follow up of 27.5 months showed:1)
    • HPV prevalence rates were 6% HPV16, 2% HPV18, 7% HPV6, 1%HPV11 with overall HPV prevalence ~50%
    • 6% of the men acquired a new HPV16 infection per year and median time to clearance was 12 months and faster in older men prsumably due to pre-existing antibodies
    • risk for having oncogenic HPV strain was 2.5x higher in those with many sexual partners or those who had anal sex with 3 or more other men, than monogamous men. Clearance was also lower in these at risk men.
    • “extrapolation from the HIM data strongly suggests that the natural history of HPV is different in men and women, with high infection and low disease rates in men and low infection and high disease rates in women.”

oropharyngeal HPV and cancer

  • ~7% of the adult population have oral HPV 2)
    • 10% of men and ~4% of women have it
  • 1% of the adult population have oral HPV type 16 which is associated with over 90% of oropharyngeal squamous cell carcinomas
  • it appears oral HPV infection is predominantly sexually transmitted
  • current smoking and intensity of smoking were independently associated with oral HPV infection, particularly among women
  • peak ages for oral HPV infection were 30–34 years and 60–64 years. This bimodal age pattern was particularly striking among men.
  • the number of HPV-positive oropharyngeal cancers diagnosed each year will surpass that of invasive cervical cancers by the year 2020
  • HPV-positive oropharyngeal tumours were increasing in incidence, now exceeding the number of these tumours caused by tobacco and alcohol abuse

ano-genital HPV:

  • see also Aust & NZ HPV guidelines 2002
  • over 30 types can infect genital area
  • HPV is highly infectious, if one member of a stable relationship has genital HPV infection, the other will be either infected or immune

clinical presentations:

  • genital warts:
    • smooth papular warts tend to occur on fully keratinised skin
    • condylomata acuminata occur most commonly on moist surfaces
    • flat-topped papular external genital warts can occur on either surface
  • cervical intraepithelial neoplasia (CIN):
    • wart virus/dysplasia on Pap smear
    • post-coital or inter-menstrual PV bleeding
  • vulvar intraepithelial neoplasia (VIN)
    • papular pruritic lesion that may be unifocal or multifocal
    • may be white, red, pigmented, usually papular but sometimes warty
  • penile intraepithelial neoplasia (PIN)
    • erythroplasia of Queyrat - Bowen's disease of glans penis
  • anal intraepithelial neoplasia (AIN)
    • Bowen's disease

differential diagnosis

  • psoriasis, seborrheic dermatitis, balanitis circinata assoc. with Reiter's syndrome
  • normal anatomy - pearly penile papules, vestibular papillae, sebaceous glands, Tyson's glands
  • acquired papules - molluscum contagiousum, lichen nitidus, skin tags, melanocytic naevi, condylomata lata

prevalence:

  • most genital infections are subclinical
  • USA women aged 15-49yrs in 1994, estimated prevalence of genital HPV infection:
    • 25% not previously infected
    • 60% past infection, not presently active
    • 10% subclinical wart virus
    • 4% wart virus in Pap smears
    • 1% visible warts
  • the prevalence of cervicovaginal HPV was 42% in women aged 14–59 years in one study, and anal HPV prevalence ranged from 42% to 57% among homosexual men3)

transmission:

  • direct skin-to-skin contact spreads HPV most efficiently
  • virus is NOT transmitted via blood or body fluids (eg. semen)
  • target cells are the mucous membranes & adjacent genital skin
  • studies among people with HPV infection show that 70% of their partners are also infected
  • transmission is common as:
    • subclinical infections are common & asymptomatic
    • warty lesions often go unnoticed, particularly in areas not easily inspected for presence of warts
    • sexual contact is most common form of transmission, but other forms include:
    • vertical transmission (unlikely mode if warts 1st appear after age 3yrs, and must also consider sexual abuse)
    • auto-inoculation from own hands
    • hetero-inoculation from hands of others (eg. caregivers of children)
    • transmission to mouth during oral sex but mouth is less hospital for genital strains than genital area
    • fomite transmission unclear - ? toilets, spas
  • if warts do not recur in the year following treatment, risk of HPV transmission is low

latency period for appearance of warts:

  • extremely variable, often warts appear after 3-6months but may be many months or even decades
  • thus development of genital warts during a long-term relationship DOES NOT NECESSARILY IMPLY INFIDELITY

prevention of ano-genital HPV infection:

  • condom usage:
    • condoms provide a physical barrier that protect the most common sites of infection but cannot prevent all genital skin-to-skin contact.
    • no evidence that condoms prevent transmission, however, condom use is recommended esp. with new sexual partners
    • regular condom use increases the cure rate of clinical & subclinical lesions, and as visible lesions are thought to be more easily transmitted than subclinical infection, it would be appropriate to advise condom use until warts are resolved.
    • why condoms may not prevent HPV infection
  • male circumcision
    • the male foreskin appears to be the main receptor site for various std's such as HIV / AIDS and hpv.
    • it is thought that the risk of female hpv infection is lower when ALL their partners had been circumcised as infants
    • however, in men with low-risk sexual behaviour and monogamous female partners, circumcision makes no difference to the risk of cervical cancer
HPV vaccine:
  • Gardasil:
    • quadrivalent HPV vaccine containing virus-like particles derived from the major capsid (L1) protein of HPV types 6,11,16 & 18.
    • introduced in Australia in 2006 & on PBS in 2007.
    • IM injection mainly for males & females aged 9-15yrs and women 16-26yrs.
  • Cervarix:
    • only covers a couple of HPV strains - types 16 and 18

HPV types associated with anogenital infection:

  • types 1-3:
    • usually cause skin warts but in children may cause ano-genital warts
  • types 6 & 11:
    • cause visible ano-genital warts as well as warts on conjunctivae, nasal, oral & laryngeal
    • intra-anal warts mainly due to receptive anal intercourse & are distinct from peri-anal warts which occur in both sexes even without anal sex
    • have low oncogenic potential & rarely associated with SCC of genital tract
  • types 16 & 18 (also 31,35,39 &41-45)
    • causes anogenital intraepithelial neoplasia & squamous cell carcinoma:
      • 70% of cervical cancers are caused by types 16 & 18
      • vulval (VIN)
      • penile (PIN/erthyroplasia of Queyrat)
      • anal (AIN/Bowen's disease) - ~90% of all anal squamous cell carcinomas are caused by infection with HPV.
      • it is thought that ~ half of all breast cancers may be associated with HPV infection, while 70% of prostate cancer samples are associated with HPV

diagnosis:

  • Pap smear for CIN
  • external warts:
    • clinical examination is sufficient to diagnose most external genital warts, if in doubt or lesions are large & confluent, or not responding to Rx, then biopsy
    • small lesions may require bright light & magnification
    • 3-5% acetic acid solutions may demonstrate subclinical lesions or flat-topped lesions via the “acetowhite test”:
      • as other lesions also become white, has low PPV & thus should NOT be used routinely to screen patients for genital wart virus infection but may show areas to biopsy or treat with diathermy
  • detection & typing of HPV has no proven benefit in Dx or Mx of external genital warts

treatment:

  • CIN:
    • colposcopy referral for ?diathermy/cone biopsy
  • external genital warts:
    • aim is to eliminate warts that cause physical or psychological symptoms
    • whilst warts are often asymptomatic, they may be painful, friable or pruritic
    • warts may be socially stigmatising or aesthetically upsetting
    • treatment can result in a clinically wart-free state but the underlying viral infection may or may not persist
    • elimination of external visible warts may not decrease infectivity since the warts may not represent the total viral burden
    • internal sites and clinically normal skin may act as reservoirs
    • if left untreated, warts may:
      • resolve spontaneously (20% do so within 6 months)
      • remain unchanged
      • increase in size or number
      • rarely progress to cancer
    • Rx options:
      • home therapy for obvious lesions:
        • imiquimod cream:
          • immune enhancer, 37-85% became wart-free after Rx and 13-19% had recurrences
          • once daily on 3 days per week onto clean, dry lesion, prior to sleep but after sex as may weaken condoms
          • wash off next morning or after 6-10hrs
          • Rx continues until resolution or max. 16weeks
          • local erythema, swelling or superficial ulceration may occur
          • less effective in circumcised men due to keratinisation of skin
          • esp. good for difficult to treat areas with carpet warts eg. female introitus, perianal area
          • not for pregnant or lactating as no data yet
        • podophyllotoxin:
          • antimitotic & causes localised tissue necrosis
          • localised epidermal pallor due to oedema occurs within 48hrs
          • 0.5% solution ⇒ 45-82% clearance within 4-6wks & 0-35% have recurrences
          • must avoid healthy skin by use of Vaseline or zinc ointment to protect it
          • bd for 2-3 consecutive days each week til resolution or max. 5 consecutive weeks
          • not for pregnant or lactating or internal use
      • cryotherapy:
        • effective for both dry & moist warts and internal as well as external
        • often considered Rx of choice in pregnancy
        • can premed with Emla cream to help reduce pain
        • 60-97% remain wart-free 3-6wks after Rx, 20-79% have recurrence
      • curettage or scissor/scalpel excisions:
        • most are exophytic & thus only need to excise down to upper dermis with haemostasis via electrosurgical unit or silver nitrate sticks
        • recurrence rates 1-35% at 1yr
      • electrocautery/diathermy:
        • requires local anaesthesia & has higher incidence of scarring
        • 22% recurrence rate
      • laser Rx:
        • expensive
      • podophyllin resin:
        • 10-25% suspension usually compounded by hospital pharmacies, but now little used
      • trichloroacetic acid:
        • caustic agent with very low viscosity which may allow it to run onto normal tissue
      • therapeutic HPV vaccines:
        • so far limited evidence of efficacy & none available yet

recurrent respiratory papillomatosis (RRP)

  • this uncommon, but potentially lethal condition has now been practically eradicated from Australia since the introduction of HPV vaccination in school children

References:

  • Aust & NZ HPV guidelines 2002
hpv.txt · Last modified: 2017/11/18 06:45 by 127.0.0.1

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