Human papillomavirus (HPV), particularly serotypes 16,18 & 33 is by far the most important factor in the development of cervical cancer. Other risk factors include:

• smoking
• human immunodeficiency virus
• early first intercourse, many sexual partners
• high parity
• lower socioeconomic status
• combined oral contraceptive pill*

*the strength of this association is sometimes debated but a large study published in the Lancet (2007 Nov 10;370(9599):1609-21) confirmed the link

Mechanism of HPV causing cervical cancer

• HPV 16 & 18 produces the oncogenes E6 and E7 genes respectively
• E6 inhibits the p53 tumour suppressor gene
• E7 inhibits RB suppressor gene

Features
- persistent biliary colic symptoms
- associated with anorexia, jaundice and weight loss
- a palpable mass in the right upper quadrant (Courvoisier sign),
- periumbilical lymphadenopathy (Sister Mary Joseph nodes) and left supraclavicular adenopathy (Virchow node) may be seen

The cervical cancer screening programme has undergone a significant evolution in recent years. For many years the smears were examined for signs of dyskaryosis which may indicate cervical intraepithelial neoplasia - management was based solely on the degree of dyskaryosis. The introduction of HPV testing allowed patients with mild dyskaryosis to be further risk-stratified, i.e. as HPV is such a strong risk factor patients who were HPV negative could be treated as having normal results.

The NHS has now moved to an HPV first system, i.e. a sample is tested for high-risk strains of human papillomavirus (hrHPV) first and cytological examination is only performed if this is positive.

Management of results

Negative hrHPV

• return to normal recall, unless
  • the test of cure (TOC) pathway: individuals who have been treated for CIN1, CIN2, or CIN3 should be invited 6 months after treatment for a test of cure repeat cervical sample in the community
  • the untreated CIN1 pathway
  • follow-up for incompletely excised cervical glandular intraepithelial neoplasia (CGIN) / stratified mucin producing intraepithelial lesion (SMILE) or cervical cancer
  • follow-up for borderline changes in endocervical cells

Positive hrHPV

• samples are examined cytologically
• if the cytology is abnormal → colposcopy
  • this includes the following results:
  • borderline changes in squamous or endocervical cells.
  • low-grade dyskaryosis.
  • high-grade dyskaryosis (moderate).
  • high-grade dyskaryosis (severe).
  • invasive squamous cell carcinoma.
  • glandular neoplasia
• if the cytology is normal (i.e. hrHPV +ve but cytologically normal) the test is repeated at 12 months
  • if the repeat test is now hrHPV -ve → return to normal recall
  • if the repeat test is still hrHPV +ve and cytology still normal → further repeat test 12 months later:
  • If hrHPV -ve at 24 months → return to normal recall
  • if hrHPV +ve at 24 months → colposcopy

If the sample is 'inadequate'

• repeat the sample within 3 months
• if two consecutive inadequate samples then → colposcopy

The follow-up of patients who've previously had CIN is complicated but as a first step, individuals who've been treated for CIN1, CIN2, or CIN3 should be invited 6 months after treatment for a test of cure repeat cervical sample in the community.