Cervical Cancer

• 6^th most common malignancy in women in Australia
• Squamous cell makes up 85-90%, adenocarcinoma 10-15%.
• Invasive cervical cancer is rare <25yo. 2 small peaks of incidence – late 30s and late 60s
• Lifetime probability in Australia is 1 in 90. 
• On average, takes at least a decade to develop from a focus of cervical squamous intraepithelial lesion
• Transformation zone is the area that almost always arises in
• HPV is found in all but 0.3% of Cervical Cancers
• Immune System clears HPV in 6 months for 50% and 2 years for 90% of women
• HPV types 16, 18 and 45 are most predominantly associated with cervical cancer, with types 16 and 18 detected in 70%–80% of cases in Australia

Risks

• Increased sexual partners
  • More than one sex partner RR>2 (RR 3 if >5 sex partners)
  • Prostitute: 4 fold increased risk 
  • Almost non-existent in virgins
• Early age of first intercourse under age 18 years (RR >2)
• Male Partner with history of multiple partners
• Tobacco use confers 1.5-3 fold increased risk (squamous cell Cervical Cancer)
• Immunosuppression
  • HIV Infection
  • Chemotherapy
  • Immunosuppressive Drugs
• Previous abnormal Pap Smear or cervical biopsy
• Lack of previous Pap Smear (50% of cancer patients)
• No Pap Smear in last 5 years (10% of cancer patients)
• History of Sexually Transmitted Disease (including HPV)
• Long term Oral Contraceptive use >5 years (2 fold increased risk)
• Lower socioeconomic class
• Uncircumcised male partner

Natural history of cervical dysplasia

• Use to be called cervical intraepithelial neoplasia (CIN), now called squamous epithelial lesion 🡪 potential for becoming invasive cervical cancer
• Progression times to cancer range from 1-30 years.  Average is 20 years. 

Presentation

• Usually on screening, usually asymptomatic. If present:
  • Vaginal bleeding, especially post-coital
  • Vaginal discharge
  • Symptoms of advanced disease, eg. Vaginal urine or flatus, weakness)

Management

• Colposcopy/Biopsy for dysplasia
• Cone biopsy – excision of cone-shaped portion of cervix
  • Includes entire transformation zone
  • Doesn’t always remove the entire lesion
• Excisional treatment with scalpel, laser or electrosurgery (eg LLETZ)
  • Large Loop Excision of the Transformation Zone – uses a thin looped wire and electrosurgical generators.
• CT, PET or MRI Pelvis may be indicated for staging
• Modified radical hysterectomy with pelvic LN sampling
• Adjuvant treatment if risk factors
  • Radiotherapy if intermediate risk factors
  • Chemoradiation if high risk factors. 

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Cervical screening

1. General Screening Recommendations

• Age: 25 to 74 years
• Frequency: Every 5 years
• Eligibility:
  • Anyone with a cervix who has ever been sexually active
  • Not required for those never sexually active
• Vaccinated individuals: Still require screening
• HPV testing:
  • Performed on liquid-based sample
  • Partial genotyping used (HPV 16/18 vs other oncogenic types)

Pathology Request Guide

Patient Presents As	Context	Age	Sample Type	Test Type	What to Write on the Pathology Request Form
Symptomatic	For investigation of symptoms – e.g. abnormal bleeding	Any age	Cervical	Co-test (HPV & LBC)	“Co-test” or “HPV & LBC”, Symptomatic
Asymptomatic	Follow-up or post-treatment for clinical management: • Following treatment of HSIL (TOC) • Following treatment of AIS • DES exposed in utero	Any age	Cervical	Co-test (HPV & LBC)	• “Co-test” or “HPV & LBC”, Test of Cure • “Co-test” or “HPV & LBC”, Post-treatment • “Co-test” or “HPV & LBC”, DE

2. Immediate Referral to Colposcopy

• Detection of HPV 16 or 18
• Cytology result: HSIL (High-grade squamous intraepithelial lesion)
• Unsatisfactory sample → Repeat within 6–12 weeks

3. Co-Test Indications (HPV + LBC)

Co-test is required if:

• Symptoms:
  • Unexplained vaginal bleeding (including post-coital, intermenstrual, or post-menopausal)
  • Persistent, unexplained vaginal discharge
  • Deep dyspareunia
• Clinical scenarios:
  • Test of Cure (TOC) after HSIL treatment
  • History of glandular abnormalities
  • Exposure to diethylstilboestrol (DES)
  • Postmenopausal bleeding of any type (refer + co-test)

Causes of Abnormal Vaginal Bleeding

Consider investigating for:

• Structural: Polyps, adenomyosis, leiomyomas
• Systemic: Coagulopathies, ovulatory dysfunction
• Malignancy-related: Endometrial disorders
• Infective: STIs
• Iatrogenic: Medications, procedures

4. Follow-Up After High-Grade Abnormalities (HSIL)

TOC Protocol (Updated Apr 2025):

Change	Detail
🧪 HPV-only testing	Cytology (LBC) no longer required
✅ 2x negative HPV tests	12 months apart → return to 5-yearly screening
Persistent HPV not 16/18	On 3 annual HPV tests → refer to colposcopy
Self-collection	Now accepted for TOC HPV tests

5. Surveillance After AIS- Adenocarcinoma in situ Treatment (Updated)

Phase	Recommendation
First 5 years	Annual co-testing; refer if any abnormality
After 5 negative co-tests	Test every 3 years
After 25 years of negative tests	<70 yrs → return to routine screening ≥70 yrs → exit program

6. Self-Collection

explain to patient:

• A self-collected sample is taken from the vagina, not the cervix.
• It is tested only for the presence of HPV (Human Papillomavirus).
• It cannot detect cell changes (such as precancerous lesions).
• The cervix is not visualised during this process.
• The self-collected sample is for HPV testing only.
• Around 6% of people tested will have HPV detected.- That means the majority of results (approx. 94%) are HPV not detected and will return to 5-yearly screening.
• If HPV 16/18 is detected → direct colposcopy.
• If other oncogenic HPV is detected → clinician-collected sample for cytology is required.

Criteria	Details
Who	Available for all eligible patients (25–74 years) who have ever had sexual contact
When not appropriate	Co-test required (e.g. abnormal bleeding) Undergoing Test of Cure Past HSIL with hysterectomy Exposed to DES
Supervision	Can be self-administered without observation
Accuracy	PCR-based HPV testing on vaginal self-sample has equivalent sensitivity to clinician-collected sample
If HPV positive	HPV 16/18 → Refer Other HPV types → Return for clinician-collected LBC

Updated April 2025 Addition:

• If a patient tests HPV+ (not 16/18) on self-collection and does not return for LBC, a follow-up self-collection is now acceptable within 9 months.
  • If this second test is HPV-negative → return to routine screening

7. Pregnancy Considerations

Cervical screening is safe at any stage of pregnancy

Modifications:

• Use spatula or swabs, avoid inserting cytobrush into cervix
• Self-collection is acceptable

If HPV is detected:

• HPV 16/18 → Refer for colposcopy
• HPV (not 16/18) → Clinician-collected LBC required for triage

8. After Hysterectomy (Updated 2025)

Type of Hysterectomy	Recommendation
Total hysterectomy for benign disease & normal screening history	Many do not need further screening.
If SCREENING required:	Annual HPV or co-testing depending on prior pathology/history. Cease after 2 negative tests on consecutive occasions.
Subtotal (cervix retained)	Continue routine 5-yearly CST

9. Immune-Deficient Populations (Updated 2025)

Now clarified and expanded. Recommend 3-yearly screening for:

• HIV
• Solid organ transplant
• Haematological malignancies
• Stem cell transplant
• Primary immunodeficiency
• Long-term haemodialysis
• ≥6 months on high-dose corticosteroids, immunosuppressants, biologics, or multiple agents

10. Colposcopy Guidance (Updated)

Situation	New Consideration
Normal colposcopy or TZ not visualised	Can consider endocervical curettage
Persistent HPV 16/18 but normal LBC & colposcopy	May defer repeat referral; safe in older, low-risk patients
Diagnostic excision (LEEP)	Not recommended if no cytologic, colposcopic, or histologic abnormality

11. Other Clinical Notes

• Cervical screening is HPV-based only — LBC alone is no longer the primary screening test
• Around 6% of screened patients will have HPV detected
• Early sexual debut (<14) – One HPV test claimable between 20–24 years
• Never-screened/under-screened – Self-collection should be routinely offered (e.g. Aboriginal/Torres Strait Islander, CALD, LGBTQIA+, rural populations)

Clinician-collected Cervical Screening Test – step-by-step instructions

1. A vaginal speculum examination is required to obtain a clinician-collected cervical sample and

visualise the cervix.

2. After the patient is prepared and comfortable, begin the speculum examination by examining the external genitalia for any abnormalities, then:
   1. warm the speculum, and apply a small amount of water-based lubricant
   2. hold the speculum in your hand with the handle facing down, and the blades closed
   3. gently part the labia and encourage the patient to breathe out while you slowly insert the closed speculum into the vagina using slight downward pressure, keeping the lower blade against the posterior wall of the vagina
   4. ask the patient if they are in any discomfort and encourage feedback throughout the procedure,
   5. open the blades just slightly, then tilt the speculum forward a little to allow maximum visualisation of the external orifice of the cervix uteri (external os).
3. Once the cervix is visualised, inspect for the following features:
   1. colour, size, shape
   2. position
   3. abnormal areas (lesions)
   4. surface characteristics
   5. the transformation zone (squamocolumnar junction; where the endocervical canal lining meets the squamous epithelium) which may or may not be visible
   6. discharge

4. The objective of cervical screening is to sample cells from the transformation zone of the cervix, where HPV is present and cell abnormalities that precede the development of squamous cell carcinoma are usually found.
5. When choosing a device(s), consider prior treatment and prior cytology results. Collect a sample of cells from the cervix using a spatula, brush or broom sampling device, following the manufacturer’s instructions. 

6. The choice of device depends on the location of the transformation zone, which is influenced by the patient’s age and menopausal status.
7. It is optimal for the cervical sample to contain both ectocervical and endocervical cells. However, the sample will not be deemed as unsatisfactory if there is no endocervical component.
8. Record the patient’s name, date of birth and ID number on the specimen vial and any other patient identifiers required by the laboratory.
9. On the pathology request form, note the following:
   1. Patient information.
   2. Cervical screening history and other relevant medical history (including gynaecological history).
   3. Any cervical abnormalities visualised during the cervical examination.
   4. Clearly indicate that the sample was clinician-collected.
   5. Patient’s Aboriginal and/or Torres Strait Islander status.
10. After sample collection, ensure the details of the consultation and procedure are accurately documented in the patient’s clinical record.

Ectropion

• Cervical ectropion is a benign gynecological condition and is regarded as a normal variant that frequently occurs in women of the reproductive age group. 
• cells from the ‘inside’ (single-layered mucus-secreting columnar cells, both ciliated and nonciliated) of the cervical canal, are present on the ‘outside’ of the vaginal portion of the cervix. (cells on the ‘outside’ of the cervix are typically multilayered stratified squamous, non keratinized epithelium)
• since the endocervical cells are more fragile and now exposed to the vaginal environment, they are more vulnerable to injury, for example, during sexual intercourse.
• It occurs due to increased exposure of the cervical epithelium to estrogen.
  •     Adolescents
  •     Pregnancy
  •     Women on hormonal contraception
  •     During the years of menstruation, most commonly seen in the ovulatory phase
• It is diagnosed on routine pelvic examination or pap screening. 
• Cervical ectropion is most commonly asymptomatic.
• In symptomatic cases, females may present with any of the following:
  • Vaginal discharge.
    • It is the most common symptom to manifest. 
    • The vaginal discharge is non-purulent and maybe white or yellow. 
    • The surface area of the mucus-secreting columnar cells is increased; therefore, women with cervical ectropion experience excessive vaginal discharge.
  • Postcoital bleeding.
    • It is seen in 5 to 25 percent of women with cervical ectropion. 
    • The fine blood vessels in the epithelium are torn very easily during sexual intercourse, leading to postcoital bleeding.
  • Cervical ectropion is one of the common causes of vaginal bleeding in the third trimester of pregnancy.
  • Intermenstrual bleeding
  • Dyspareunia
  • Pelvic pain
  • Recurrent cervicitis
  • Backache
  • Micturition disturbances
• Management
• requires no treatment unless the symptoms are affecting the patient’s daily life. 
• First-line treatment
  • discontinuing hormonal contraceptives like oral contraceptive pills, depot medroxyprogesterone acetate, and switching to nonhormonal contraception methods
  • If the symptoms persist, the following treatment can be offered:
    • Cautery 
    • Microwave tissue coagulation. 
    • Boric acid vaginal suppositories can be used to make the pH acidic.

HPV vaccination

• Age:
  • from 9 years of age and onwards
  • The optimal age for HPV vaccination is around 12–13 years prior to exposure to HPV 
  • most effective if the vaccine is given early in adolescence
• Used to be 2 dose schedule
• From 6 February 2023
  • the routine 2-dose HPV vaccine schedule provided to young people aged 12 to 13 years will become a single dose schedule
  • NIP-funded catch-up program extended up to and including 25 years of age (increased from 19 years of age)
• immunocompromised
  • should still receive 3 doses of the HPV vaccine – 0, 2, 6 months
  • funded under the NIP before 26 years of age
  • Severely immunocompromising conditions include:
    • primary or secondary immunodeficiencies (complete or partial deficiencies of B-lymphocyte antibody or T-lymphocytes)
    • HIV infection
    • malignancy
    • organ transplantation 
    • significant immunosuppressive therapy
    • (excluding those with asplenia or hyposplenia)
• MSM
  • HPV vaccine is recommended for men who have sex with men (MSM) of any age who have not previously been vaccinated
• Age >26
  • may benefit from being vaccinated 
  • 3 doses are recommended – 0, 2, 6 months
  • Vaccines need to be purchased via private prescription for people aged 26 years and over, and costs may vary. 
• Vaccines available in Australia
  • 2vHPV Cervarix – HPV types 16 and 18
  • 9vHPV Gardasil – HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58
• Gardasil 9vHPV
  • Registered for use in females aged 9 to <46 years and males aged 9 to <27 years.
  • Recombinant protein particulate (VLP) vaccine containing the major capsid (L1) protein of HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58
• Contraindications and precautions
  • anaphylaxis after a previous dose of any HPV vaccine
  • anaphylaxis after any component of an HPV vaccine
  • anaphylaxis to yeast (for 9vHPV)
  • Pregnancy
    • HPV vaccines are not recommended for pregnant women, due to an absence of evidence of vaccine use in large populations of pregnant women.
  • Breastfeeding
    • can receive HPV vaccines
  • Adverse events
    • Headache , fever
    • nausea
    • dizziness, fatigue
    • Guillain–Barré syndrome – possible very small risk (approx. 1 in 100,000 girls vaccinated) 

Human papillomaviruses 

• are small, non-enveloped viruses with circular double-stranded DNA. 
• They infect and replicate primarily within cutaneous and mucosal epithelial tissues.
• More than 100 HPV genotypes have been fully sequenced. 
• Approximately 40 HPV types specifically infect the anogenital tract
• Pathogenesis
  • HPV requires a breach in the epithelial surface to enter the basal epithelial cells and cause infection. 
  • However, infectious virions are only produced in the terminally differentiated layer of the epithelium.
  • high risk –
  • HPV types 16, 18, 31, 33, 35, 45, 52 and 58 are high risk because they can cause cancer. 
  • The most oncogenic HPV type is HPV-16. This is the most frequent cause of HPV-related cancers.

• High-risk HPV types may cause dysplasias and cancers of the:
  • cervix
  • vulva
  • vagina
  • penis
  • anus
  • oral cavity
  • oropharynx
• Dysplasias may be:
  • low grade — the viral cytopathic effect of HPV infection
  • high grade — precursors to cancer
• Low risk –
  • HPV types 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81 and 89 are low risk. 
  • These are mostly associated with non-malignant lesions such as genital warts
  • may cause lesions such as:
    • cutaneous warts
    • genital warts
    • respiratory papillomatosis
      • is potentially fatal. It is characterised by multiple warty growths on the mucosal surface of the respiratory tract
• Transmission
  • Anogenital HPV is mainly transmitted through sex. 
  • Less commonly, the virus can be transmitted after intimate non-penetrative sexual contact
  • Perinatal transmission of HPV can result in laryngeal infection in infants. 
  • In rare cases, this can lead to recurrent respiratory papillomatosis.
• Most people clear genital HPV infections (that is, the infection is no longer detectable by HPV DNA testing) within 12–24 months. 
• However, in some cases, the virus is thought to remain as a latent infection even though DNA is no longer detectable.
• In about 3–10% of infections, the virus persists. 
• People with persistent HPV infection are at risk of developing HPV-associated cancers.