Human Papillomavirus Infections

• Introduction.
• Mucosal HPV infection.
  • Oral warts.
• Skin warts.

Introduction

• Human Papillomavirus (HPV) is a small DNA virus that only infects humans.
• Spread is via direct contact:
  • New lesions are probably more infective than older, established lesions.
• The HPV genome exhibits considerable variation that has allowed description of closely-related HPV types:
  • At least 75, and probably over 100 HPV types occur.
  • Individual HPV types are designated by a number. For example, HPV16.
  • Identification of different HPV types has given considerable insight into disease pathogenesis.
• HPV was named because of an association with small epithelial proliferations:
  • 'Papilla' = nipple (Latin).
  • 'Oma' = tumour (Greek).
• HPV cannot be efficiently propagated in cell culture:
  • Little is understood about HPV biology, although it appears to be complex.
  • This lack of insight has limited the development of new therapies for management of HPV diseases.
• It is known that HPV infects stratified squamous epithelium and that:
  • Some HPV types predominantly infect mucosa (at least 30 different HPV types infect mucosa).
  • Other HPV types primarily infect skin (at least 35 different HPV types infect skin).
• Asymptomatic HPV infection is common:
  • For example, in one study of sexually-active men and women (aged 15-49 years old):
    • 75% had evidence of prior or current genital HPV infection.
• Under poorly defined circumstances, HPVs cause disease including:
  • Focal epithelial proliferation which manifests clinically as 'warts'.
  • Carcinoma.
    • The links between HPV and cervical carcinoma have been extensively investigated.
      • Cervical carcinoma mostly affects young women and globally is the third most common cancer in women.
      • Most cervical cancer is associated with infection of a small group of HPV types (e.g. HPV16).
    • Despite intensive investigation, no link between HPV infection and oral carcinoma has been established.
• Development of vaccines against HPV infection have been driven by the belief that effective vaccination could dramatically reduce the incidence of cervical carcinoma.
  • Several vaccines against HPV have entered clinical trials.
  • It is currently unknown whether any of these will go on to be used in mass immunisation programmes.
• HPV infections are of direct relevance to the practice of dentistry as:
  • Appropriate Cross Infection practices will prevent unnecessary spread of HPV infections in the dental surgery.
    • This relates to skin and mucosal warts.
  • A patient may present with oral mucosal warts, or warts may be noticed as a coincidental finding during other dental treatment.
    • Oral mucosal warts may arise as a consequence of sexual transmission (oro-genital transmission).
  • The presence of one sexually-transmitted disease (STD) is associated with a high risk of the presence of other STDs including HIV:
    • Oral mucosal warts can be an early sign of HIV infection, and other oral stigmata of HIV Infection should be actively looked for.
    • In contrast to other oral manifestations of AIDS, warts do not regress in response to drugs used to treat AIDS (HAART) and often increase in number and severity.

Mucosal HPV Infection

• Mucosal HPV infection is common and mostly asymptomatic.
• Spread is via direct contact, and this is a key determinant of which mucosal sites are involved. These may include
  • Oral, genital, anal, nasal, ocular or other mucosae.
• Clinically obvious lesions manifest as exophytic, or less frequently flat lesions that are commonly referred to as 'warts'.
  • The term 'condyloma acunimatum' may be encountered:
    • This primarily refers to exophytic, fronded genital warts, but is occasionally used to describe oral warts that have been acquired due to sexual transmission.
      • 'Condyloma' = anogenital.
      • 'Acunimatum' = exophytic.

Oral Warts

• Oral mucosal warts can occur at any site, but particularly involve the:
  • Hard or soft palate, or uvula.
• Lesions are generally small (<5mm) and may be:
  • Asymptomatic.
  • Associated with minimal symptoms such as awareness of a small, painless lesion.
    • Secondary trauma may cause minor discomfort.
• Typically there are only one or a few discrete oral warts present at any point in time.
• Lesions may have several different appearances:
  • Exophytic warts with hyperkeratosed fronds.
  • Dome-shaped sessile papules that may be the colour of normal mucosa or be white due to hyperkeratosis.
  • Flat-topped sessile papules that are only slightly raised above the surface and are generally the colour of normal mucosa.
    • If these are multiple, consideration should be given to a possible diagnosis of Focal Epithelial Hyperplasia (Heck's Disease).
      • This is rare in the U.K., but does occur.
      • It is common in some populations (e.g. Eskimo & Venezualan Indians).
      • Caused by HPV13 & HPV32 in susceptible individuals.
• Reference has already been made as to the relevance of oral warts to the practice of dentistry.
  • Not all oral warts arise as a consequence of oro-genital sex, but this possibility has to be considered.
• The clinical diagnosis of an oral wart can be confirmed by excision biopsy and histopathology.
  • Once the diagnosis has been confrmed, other warts or recurrent warts may be removed or destroyed by several different means including:
    • Excision.
    • Cryotherapy (freezing with a probe cooled by liquid nitrogen).
    • Laser vaporisation.
  • Once the diagnosis has been confirmed, not all patients will want such intervention.
• Recurrence of oral warts may occur or new warts develop elsewhere in the mouth:
  • Some patients undergo multiple courses of treatment for oral warts.
• Oral warts may spontaneously regress with time, although this cannot be predicted with certainty in individual patients.

A. An exophytic wart with a smooth surface. B. By contrast, this wart has long, hyperkeratosed fronds. C. Oral warts can be florid as in this patient where a large number of discrete warts involve soft palate. D. An exophytic wart involving the red part of the upper lip.

Skin Warts

• More common than mucosal warts and may involve any part of the skin including:
  • The fingers of members of the dental team.
  • Facial skin.
• Skin warts have different clinical appearances and associations with different HPV types.
  • Exophytic warts with hyperkeratosed fronds.
  • Sessile papules that may be dome-shaped or relatively flat.
  • Keratotic warts that form a thick keratinised crust.
  • Deep warts including verrucas.
• A range of non-surgical and surgical treatments are available.
• Coverage of a wart (e.g. a waterproof plaster on a dentists finger) will prevent the transmission of skin warts in the dental practice.

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