Cervical Screening & Cancer Prevention

• Cervical screening presented on 27 March 2024, by Dr. Ronan Daly, RCSI O&G Clinical Tutor at Rotunda Hospital

Cervical Smear Testing

• Strategies for cervical cancer prevention should be described
• Explain and compare HPV and cervical cytology screening methods
• Explain and demonstrate how cervical screening is performed
• Describe how to manage negative and positive screening results

HPV and Cervical Cancer

• Describe the epidemiology and pathology of pre-malignant cervical disease

Colposcopy

• Explain how and why colposcopy is performed
• Describe how pre-malignant cervical disease is treated

Anatomy of Cervix

• Fallopian or uterine tube location
• Ovary position
• Uterus location
• Cervix position
• Vagina location
• Ectocervix projects into the vagina, with stratified squamous non-keratinized epithelium
• Endocervix connects the vagina and uterus with simple columnar glandular epithelium
• The transformation zone is the squamocolumnar junction between the ectocervix and endocervix

Cervical Cancer Origins and Types

• Most originate in the transformation zone
• Most cervical cancers (up to 90%) are squamous cell carcinomas located in the ectocervix and caused by Human Papilloma Virus (HPV)
• Cervical adenocarcinomas develop in glandular cells of the endocervix and are rarer

Human Papilloma Virus (HPV) Facts

• Double-stranded DNA virus spread through skin contact

• Most spread through sexually transmitted disease

• Types include:

  • 2, 7, 22 - associated with common warts
  • 1, 2, 4 - associated with plantar warts
  • 6, 11, 42 - associated with anogenital warts
  • 16, 18, 31, 35, 45 - associated with genital cancers
    • These are oncogenic (high-risk) subtypes

• HPV leads to squamous metaplasia, then to dysplastic changes in the transformation zone, then to cervical intraepithelial neoplasia, and finally to cervical cancer

Cervical Cancer Prevention

• HPV is associated with over 90% of cervical cancers
• Methods of prevention include cervical screening and Human Papilloma Virus (HPV) vaccination
• Gardasil 9 is an adjuvanted non-infectious recombinant 9-valent HPV vaccine
• HPV vaccination protects against against HPV infection
• HPV vaccination has almost eliminated cervical cancer in women and people with a uterus born since September 1st 1995
• HPV vaccination is offered at 12-13 years of age to all children, two doses over 6 months
• Over 100 million people vaccinated, 400,000 in Ireland
• There are no safety concerns or long term adverse events with the HPV vaccine

Screening Suitability

• To be suitable for screening, a condition should fulfill the following requirements:
  • represent an important health problem
  • natural history should be adequately understood
  • recognizable latent or early symptomatic stage
  • suitable test which is acceptable to the population
  • accepted treatment for patients
  • facilities for diagnosis and treatment
  • economically balanced
• Junger Wilson Criteria for Screening Programmes was created in 1968

Cervical Screening Specifics

• Aims to identify premalignant phase of cervical cancer and treat at that stage
• Incidence and mortality from cervical cancer have fallen since screening programs were introduced
• Countries are moving to HPV-based screening programs
• The screening test involves taking a sample of cells from the cervix and testing these cells for HPV:
  • if positive, the cells are assessed for cytological abnormalities (i.e. dyskaryosis)
  • if negative, no further testing is required or performed
• HPV screening is a better method than previous cytology-based screening methods since it allows to detect precancerous lesions and requires a greater screening interval

Smear Tests

• Are provided to women 25 - 65
  • introduced in Ireland in March 2020
  • In women and people with a cervix aged 25 - 29, screening is performed every 3 years
  • In women and people with a cervix aged 30 - 65, screening is performed every 5 years

Cytology Results following HPV Screening

• Reflexive cytology is only performed if HPV is positive
• Bethesda Classification includes
  • Low-grade squamous intraepithelial lesion (LSIL) which features mild dyskaryosis and Usually corresponds to CIN 1
    • Requires colposcopy referral, usually regresses within 24 months without treatment in most patients
  • High-grade squamous intraepithelial lesion (HSIL) which features moderate to severe dyskaryosis and usually corresponds to CIN 2 or 3
    • Requires colposcopy referral and treatment
  • Atypical squamous cells of underdetermined significance (ASCUS)
    • Do not fulfil criteria for above but require follow-up
• Following a positive test, any HPV positive result that is found to be abnormal is referred to colposcopy for further evaluation

Colposcopy Procedure

• Outpatient procedure
• Patient placed in the lithotomy position and a cuscos speculum is inserted to visualize the cervix
• Cervix is closely examined using a biocular microscope called a colposcope
• Application of acetic acid to cervix
  • Acetic acid dehydrates cells
  • Abnormal areas appear white (aceto-white) due to decreased glycogen and increased protein
• Application of iodine (Schiller’s test)
  • Iodine is taken up by normal cells with a high glycogen content
  • Abnormal cells do not take up iodine and remain white
• A small punch biopsy may then be taken, which is used to give a histological diagnosis
• “See and treat" option may be offered when a Large Loop Excision of the Transformation Zone (LLETZ) is performed under local anaesthetic
• Follow up is crucial (usually 6 months post treatment)

Cervical Intraepithelial Neoplasia

• CIN is a precancerous lesion, diagnosed by histopathological examination of a colposcopically-directed tissue biopsy with the following features:
  • Loss of cellular differentiation
  • Disordered cellular maturation involving squamous epithelium
  • Basement membrane is not involved
• Grading:
  • CIN 1 involves lower 1/3rd of epithelium
  • CIN2 involves lower 2/3rd of epithelium
  • CIN 3 involves whole thickness of epithelium
• Treatment Options:
  • Excisional if CIN II/III is found on punch biopsy or is suspected at colposcopy
    • Options include LLETZ, cone biopsy, which requires general anaesthesia
  • Ablative if no evidence of glandular abnormalities, invasive disease or high grade CIN
    • Includes cold coagulation
• Prognosis
  • CIN 1 abnormal cells will likely regress. Follow-up smear at 1 year
  • CIN 2 has a higher risk of progression to cervical cancer. Requires treatment (ablation or excision)
  • CIN 3 has the highest risk of progression to cervical cancer. Requires treatment (e.g., LLETZ)

Main Learning Points

• Prevention of cervical cancer is focused on HPV infection as a cause, reflected in both vaccination and screening strategies
• Implemented strategies have reduced the incidence and mortality of cervical cancer, with many countries on track to eliminate the disease in the coming decades

Acknowledgements

• Dr Niamh Daly and Ms Claire Thompson