Key content
 Human papillomavirus (HPV) is associated with neoplastic disease at sites other than the cervix.
 Cancer caused by HPV may behave differently to other cancers at the same site.
 The presence of HPV alone is not sufficient to demonstrate a causal association.
 HPV vaccination has the potential to impact on disease burden beyond cervical cancer.
Learning objectives
 To understand the spectrum of disease caused by HPV.
 To review the management of HPV-associated disease in pregnancy.
 To be aware that future research into HPV-related disease may alter management.
Ethical issues
 What advice should women be given regarding their sexual partners?
 Should boys be offered HPV vaccination?
Keywords: genital warts / human papillomavirus / intraepithelial neoplasia / vaccination / vulval cancer

The recent Nobel Prize winner in Physiology or Medicine,
Harald zur Hausen, first hypothesised a role for human
papillomavirus (HPV) in the development of cervical
cancer.1 Since the 1970s HPV has been proposed as a
causative factor in a variety of benign and malignant diseases.
HPV is a non-enveloped double-stranded DNA virus that
infects the epithelial basal layer. The majority of HPV
infections occur without symptoms and are cleared by the
host over 8–12 months. However, infection may persist,
resulting in intraepithelial neoplasia and, over time,
progression to invasive carcinoma.
One hundred and twenty different types of HPV affecting
humans have now been described.2 HPV has been identified
in various benign and malignant lesions within anogenital
sites, the aerodigestive tract, skin and conjunctiva.3 There
are extensive data in the literature regarding HPV and
cervical disease. Walboomers et al.4 reported that the
worldwide prevalence of HPV in cervical carcinomas is
99.7%. The burden of HPV in non-cervical disease has been
increasingly recognised and this review will summarise the
evidence available.

Diseases commonly associated with individual HPV types
HPV type Disease
1, 2 Verruca vulgaris
1, 2 & 4 Plantar warts
3, 10 Flat cutaneous warts
5, 8 Carcinogenesis in epidermodysplasia verruciformis
6, 11 Anogenital warts, respiratory papillomatosis
16, 18 Anogenital neoplasia, oropharyngeal cancers

Management of genital warts in pregnancy
 Warts often grow in size and number or may appear for the first
time during pregnancy.
 The aims of treatment are symptom relief and minimising the
number of lesions present at delivery.
 Treatment options include laser, diathermy, surgical excision and
trichloroacetic acid.
 Most topical treatments should be avoided because of possible
teratogenic effects.
 Only in severe cases should caesarean delivery be considered.
 There is an extremely small risk of their child developing recurrent
respiratory papillomatosis.

Establishing causal links between HPV and cancer
Certain criteria must be met to confirm a causative link between HPV and
a cancer. The basis for this are Koch postulates published in 189053 (for
bacterial disease). These postulates can be adapted for HPVand cancer:54
1. Is HPV infection found in affected patients?
2. Are viral genes found in cancer cells?
3. Can the cancer be linked to the presence of an active viral gene
product, for example, an oncogene?
4. Does prevention of the infection stop the cancer, for example, by

Should we vaccinate boys?
Arguments for:
 Herd immunity obtained by vaccinating only women is likely to be
insufficient to eradicate the targeted HPV types.
 Increased protection from non-cervical HPV disease, particularly in
men who have sex with men risk groups.
 Reduced disease burden on the NHS, particularly if a quadrivalent
vaccine is used.
Arguments against:
 Increased costs of extending the vaccination programme to prevent
relatively few non-cervical malignancies.
 Targeted screening instead of widespread vaccination may be more
appropriate for high-risk groups.

HPV causes disease in many non-cervical sites, the full extent
of which has not been fully established. Our traditional
anatomical approach to the management of cancers may be
replaced by a system related to disease aetiology that will
allow improved management strategies.
The management of HPV-associated disease in pregnancy
necessitates a modified approach. The treatment as well as
the counselling given should be individualised to the patient.