Cervical Smears and Cancer Screening

Learning Objectives

• Understanding the basis of the cervical smear is key
• Understanding cervical screening is key
• Understanding reasons for referral to colposcopy is essential
• Being able to describe colposcopy to a patient is part of the education
• Understanding treatments at colposcopy clinic is a key element

Skills Objectives

• It is important to See a cervical smear done
• Be able to demonstrate the act of taking a cervical smear with a pelvic model
• Attending a colposcopy clinic is helpful

Cervical Cancer Facts

• Approximately 450,000 cases of cervical cancer occur worldwide each year
• Lifetime cervical cancer risks:
• 5% in Africa, India, Latin America
• 1% in Europe and North America
• Roughly 3000 cases of cervical cancer are diagnosed annually in the UK with 1300 deaths
• About 180 cases of cervical cancer are diagnosed annually in Ireland, with 80 deaths

Cervical Cancer Screening

• Screening identifies and treats the premalignant phase
• Cervical cancer incidence and mortality have decreased since screening programs began
• Australia and Rwanda are approaching cervical cancer eradication through HPV vaccination and screening

Irish National Cervical Screening Programme (CervicalCheck)

• Screening provides smear tests to women aged 25-65
• HPV cervical screening, introduced in Ireland in March 2020, is a new screening method
• It first identifies high-risk human papillomavirus (HPV) types that can cause cervical cancer
• If HPV is found, the sample is checked for abnormal cells
• Benefits of HPV cervical screening:
• Improved screening method
• Prevents more cancers
• Reduces the need for frequent tests

HPV vs Cytology cervical screening

• If 1,000 people are screened, about 20 will have abnormal (pre-cancerous) cervical cells
• The old smear test can find 15 of these 20 people, and 5 people wont be found and may develop cervical cancer
• new HPV cervical screening can find 18, and 2 people wont be found and may develop cervical cancer
• Less frequent assessments are possible using HPV screening
• 25-29 year olds: every 3 years
• 30-65 year olds: every 5 years (cytology screening every 3 years to 44yo)

Transformation Zone

• Cervical Intraepithelial Neoplasia develops there
• The cervix is histologically divided into the endocervix and ectocervix
• Columnar epithelium lines the endocervix, squamous epithelium lines the ectocervix, and their junction is the squamocolumnar junction

Transformation Zone Changes

• Under the influence of oestrogen, part of the endocervix everts, exposing columnar epithelium to the vaginal environment
• pH changes cause the columnar epithelium to transform into squamous epithelium via metaplasia
• CIN develops in this transformation zone and is sampled when performing a cervical smear

Taking a Cervical Smear

• Ideally, smears are taken during the mid-to-late follicular phase of the menstrual cycle
• A Cusco's speculum allows identification the cervix
• A cervical brush or wooden ‘Aylesbury’ spatula is used for sample collection, especially for liquid-based cytology
• A cervical brush collects cells from the squamocolumnar junction using a 360-degree sweep
• The sample is suspended in a buffer and processed into a thin layer on a slide, free from blood or debris

Terminology for Reporting

• Cytology screening results:
• Dyskaryosis: mild, moderate, or severe
• Bethesda System: LSIL, HSIL, or Atypical results
• HPV screening results:
• High-risk (14 subtypes) HPV detected or not
• If detected, reflex cytology is performed

Results from screening

• HPV screening:
• HPV not found: Routine recall
• HPV found (14 high-risk subtypes) and no abnormal cell changes: Repeat test in 12 months
• HPV found and abnormal cell changes: Colposcopy
• Inadequate sample
• Cytology screening:
  • Borderline Nuclear changes: Usually associated with HPV infection or atrophic vaginitis
  • Low grade (mild/moderate) dyskaryosis
  • High grade (moderate/severe) dyskaryosis
  • Atypical

Low Grade/Mild Dyskaryosis

• Usually corresponds to CIN 1
• HPV changes
• CIN regresses without treatment in 60% of women within 24 months

High Grade (Moderate Dyskaryosis)

• The moderate group is no longer reported as either low or high grade
• 75% of these women have CIN 2-3

High Grade (Severe Dyskaryosis)

• Cells have abnormal cytoplasmic maturation and a high nuclear:cytoplasmic ratio
• All women with severe dyskaryosis need to be referred for colposcopy
• 80-90% will have CIN 2-3 at colposcopy

Atypical Cells

• Cytological changes in squamous cells are are not normal and do not meet the squamous intraepithelial changes criteria and are classified as atypical squamous cells (ASC)
• ASC-US means 'Atypical Squamous Cells of Undetermined Significance'
• ASC-H means 'Atypical Squamous Cells of Undetermined Significance but high grade changes cannot be ruled out'

Atypical Glandular Cells

• Smears detect glandular cells, raising the possibility of cervical adenocarcinoma
• Adenocarcinoma may arise from the endocervix or endometrium
• AGC 'Atypical Glandular Cells': The glandular cell type is specified as endocervical, endometrial, or glandular
• AGC Favour Neoplastic 'Atypical Glandular Cells Favour Neoplastic Process': Glandular cell type specified as endocervical or not specified

Intraepithelial Neoplasia

• A process from atypical changes to dysplastic changes and invasive carcinoma
• It is a histological diagnosis
• The more severe the lesion, the less likely it is to revert to normal
• In the cervix this neoplastic lesion starts at the transformation zone near the squamocolumnar junction

Cervical Intraepithelial Neoplasia

• This is a histological diagnosis
• CIN 1: Involves lower 1/3rd of epithelium
• CIN 2: Involves lower 2/3rd of epithelium
• CIN 3: Involves whole thickness of epithelium

Assessing CIN under Colposcopy

• CIN 1 is a Faint Acetowhite with poorly defined borders
• CIN 2 is a Dense acteowhite, regular borders and no vascular markings
• CIN 3 is Dense acetowhite with well defined borders, abnormal vascular patterns: coarse punctuations and mosaic. 30% will develop invasive cancer if left untreated for 18 years

Colposcopy in Invasive Disease

• Colposcopy reveals: Thick acetowhite, Punctuations, Mosaicism, Abnormal branching vasculature

Risk Factors for Cervical Cancer

• Early onset of sexual activity
• Multiple sexual partners
• Smoking
• History of STI
• Immunosuppression impairs HPV elimination: HIV, autoimmune diseases, immunosuppressive drugs, transplant patients
• Low socioeconomic status

Colposcopy Procedure

• It is an outpatient procedure where the cervix is closely examined using a biocular microscope (colposcope)
• The patient is placed in the lithotomy position, a Cusco's speculum is inserted to visualize the cervix, and acetic acid is applied

Indications for Colposcopy Referral

• Once HPV is detected, cervical cytology will determine the next step
• Referrals: ASCUS or worse (i.e., all LSIL and HSIL), second negative cytology after two positive HPV screens, HIV-positive and HPV-detected, discharged from colposcopic surveillance with increased HPV screening, third indeterminate screening result
• Urgent Referral Criteria: If the cervix is suspicious for cancer, do not perform a screening test, and make an urgent referral to the colposcopy service

Features during Colposcopy

Colposcopic features include:

• Degree of acetowhite staining of cervix
• Punctations (vascular prominence)
• Mosaicism (branching of tree pattern)
• Abnormal vessels
• Abnormal epithelium such as CIN has increased amount of protein and lower levels of glycogen than normal epithelium
• Acetic acid application coagulates protein and makes abnormal cells appear acetowhite
• A 'mosaic' pattern may appear with patches of acteowhite separated by areas of red vessels

Lugol's Iodine in Colposcopy (Schiller's Test)

• Lugol’s iodine stains glycogen brown in normal cells
• Columnar cells do not contain glycogen; thus, they do not stain with iodine
• Immature metaplastic cells in the transformation zone have less glycogen and may not stain
• Abnormal cells have less glycogen and take up less iodine

Management of CIN

• Treat immediately based on colposcopic impression (see + treat) or confirm diagnosis
• Treatment Options: Excisional or Ablative
• The most common method is large loop excision of the transformation zone (LLETZ), usually in the clinic
• The cervix is infiltrated with local anaesthesia
• The TZ is excised using a diathermy loop, and the specimen is sent for histological analysis

Ablative Techniques

• Ablative techniques are suitable only:
• When the entire transformation zone is visualized
• If there is no evidence of glandular abnormality
• If there is no evidence of invasive disease
• If there are no major discrepancies between cytology and histology

LLETZ & LEEP

• LLETZ (Large Loop Excision of the Transformation Zone)
• LEEP (Loop Electrosurgical Excision Procedure)
• Both terms refer to the same procedure; LLETZ is used in Europe, while LEEP is common in North America

Follow Up is key

• Any woman diagnosed with CIN, is at an increased risk of developing cervical cancer weather they have been treated for it or not
• Regular follow up is an essential, by cytology
• Protocol starts six months post-treatment and includes a test of cure protocol

HPV Vaccines

• Prophylactic vaccines against HPV 6,11,16,18 have been developed
• The HPV vaccine is safe, with over 13 years of studies and over 1 million participants in clinical trials since 2006 with over 90 pieces of research about HPV vaccine safety and effectiveness available
• Vaccines on the Market: Gardasil and Cervarix
• Both vaccines protect against HPV types 16 and 18, which can cause cervical cancer and some other genital cancers
• The current HPV vaccine in Ireland is Gardasil 9, with over 100 million fully vaccinated worldwide, including over 260,000 in Ireland
• Gardasil protects against two HPV types causing genital warts