Cervical Cancer
- 6th 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.
Cervical screening
1. General Screening Recommendations
1. General screening recommendations
| Item | Recommendation |
|---|---|
| Age | 25–74 years |
| Frequency | Every 5 years if HPV not detected |
| Who | Women and people with a cervix who have ever had any sexual contact |
| Never sexually active | Very low risk; routine screening generally not required, but discuss/document individual circumstances |
| HPV vaccinated | Still requires routine screening |
| Primary test | HPV test with partial genotyping: HPV 16/18 vs other oncogenic HPV |
| Sample options | Self-collected vaginal sample or clinician-collected cervical sample |
| Exit | Exit test between 70–74 years if adequately screened |
The NCSP guideline is HPV-based and applies to people aged 25–74 with a cervix; the 2025 update took effect from 14 April 2025
Pathology Request Guide
| Sample | What it can test | Key point |
|---|---|---|
| Self-collected vaginal swab | HPV only | Does not provide cytology/LBC. Cervix is not visualised. |
| Clinician-collected cervical liquid-based sample | HPV ± reflex LBC / co-test | Needed when cytology is required. |
| Co-test | HPV + LBC | Requires clinician-collected sample from the cervix. |
2. Immediate Referral to Colposcopy
| Finding | Management |
|---|---|
| HPV 16/18 detected | Refer for colposcopy |
| HPV not 16/18 + LBC pHSIL/HSIL | Refer for colposcopy |
| HPV not 16/18 + glandular abnormality | Refer for colposcopy |
| Suspicious cervix on examination | Urgent gynaecology/colposcopy referral, regardless of CST result |
| Cytology suspicious for invasive cancer | Urgent gynae-oncology referral |
| Unsatisfactory sample | Repeat test as soon as practicable, usually 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 treated HSIL / CIN2 / CIN3 — updated 14 April 2025
| Step | Recommendation |
|---|---|
| Start | 12 months after treatment |
| Test | Annual HPV test only |
| Cytology/LBC | No longer routinely required for HSIL Test of Cure |
| Completion | Two consecutive annual HPV-not-detected results |
| After completion | Return to routine 5-yearly screening |
| Self-collection | Accepted for Test of Cure HPV testing |
| Retrospective application | People already on old ToC pathways may now have met criteria and be returned to routine screening by NCSR |
The 2025 update changed post-treatment HSIL Test of Cure from co-testing to annual HPV tests until two consecutive negative results, then return to routine screening.
| Result during ToC | Action |
|---|---|
| HPV not detected | Continue until 2 consecutive annual HPV-negative tests |
| HPV detected | Manage according to NCSR/NCSP pathway; often requires clinician-collected sample, cytology triage and/or colposcopy depending HPV type, history and results |
| HPV 16/18 detected | Usually colposcopy pathway |
| Positive margins after treatment | May need individualised specialist pathway; annual co-testing may be considered case-by-case |
Avoid simplifying this as “persistent HPV not 16/18 on 3 annual tests → colposcopy” for all patients.
The exact pathway depends on whether this is routine screening, post-treatment Test of Cure, prior results, HPV type and NCSR recommendation.
5. Surveillance After AIS- Adenocarcinoma in situ Treatment (Updated)
| Phase | Recommendation |
|---|---|
| First 5 years | Annual co-testing |
| After 5 negative annual co-tests | Extend to 3-yearly co-testing |
| After 25 years of negative surveillance | If <70 years: return to routine screening |
| If ≥70 years | Can exit if at least one co-test at age ≥70 shows HPV not detected and LBC negative |
The 2025 update allows AIS surveillance to move from annual co-testing to 3-yearly testing after 5 negative annual co-tests, and surveillance can cease 25 years after completely excised AIS if criteria are met.
If AIS margins incomplete or unclear
Do not simply follow routine surveillance. Usually needs specialist management and consideration of further excision to achieve clear margins.
6. Self-Collection
A self-collected Cervical Screening Test is a vaginal swab.
It tests for HPV only.
It does not look at cervical cells, does not detect cell changes directly, and the cervix is not visualised.
Most people will have HPV not detected and return to routine 5-yearly screening.
If HPV is detected, follow-up depends on the HPV type.
| Result from self-collected sample | Management |
|---|---|
| HPV not detected | Return to routine 5-yearly screening |
| HPV 16/18 detected | Refer for colposcopy |
| HPV not 16/18 detected | Needs clinician-collected cervical sample for LBC triage |
| HPV not 16/18 detected and patient does not return for LBC | From 14 April 2025, can offer a repeat self-collected HPV test as follow-up if 9 months or more since initial CST |
| Repeat self-collected follow-up HPV test is negative | Return to routine screening |
The 2025 update specifically allows people with HPV not 16/18 detected on self-collection who do not return for follow-up after 9 months or more to be offered a self-collected HPV follow-up test rather than a co-test.
When self-collection is appropriate
| Suitable | Not suitable / clinician collection preferred |
|---|---|
| Routine asymptomatic screening | Abnormal vaginal bleeding |
| Under-screened or never-screened patients | Persistent unexplained discharge |
| Patients who decline speculum examination | Suspicious cervix |
| Test of Cure after treated HSIL, under 2025 update | AIS surveillance |
| Pregnancy routine screening | DES exposure in utero |
| Patients with trauma, cultural, access or comfort barriers |
7. Pregnancy Considerations
| Situation | Recommendation |
|---|---|
| Due for routine CST | Cervical screening is safe in pregnancy |
| Sample option | Self-collection is acceptable |
| Clinician collection | Avoid endocervical brush/cytobrush insertion into cervical canal; use appropriate pregnancy technique |
| HPV 16/18 detected | Refer colposcopy |
| HPV not 16/18 detected on self-collection | Clinician-collected LBC needed for triage |
| Treatment of CIN in pregnancy | Usually deferred unless invasive cancer suspected; specialist colposcopy managemen |
8. After Hysterectomy (Updated 2025)
| Hysterectomy type / history | Recommendation |
|---|---|
| Subtotal hysterectomy — cervix retained | Continue routine 5-yearly CST |
| Total hysterectomy for benign disease, no CIN2+/AIS/cervical cancer, satisfactory screening history | Usually no further screening |
| Total hysterectomy with no prior screening / unknown history | May need follow-up testing; check NCSR/NCSP pathway |
| Total hysterectomy with LSIL or HSIL in hysterectomy specimen | Annual HPV testing until oncogenic HPV not detected on two consecutive occasions |
| Total hysterectomy with previous biopsy-confirmed HSIL and ToC not completed | Annual HPV testing until two consecutive HPV-not-detected results |
| Total hysterectomy with previous AIS or AIS in hysterectomy specimen | Annual co-testing until two consecutive tests are both negative |
| Previous cervical cancer / genital tract malignancy | Specialist-led vault surveillance |
The 2025 update states that after total hysterectomy most people with no evidence of biopsy-confirmed AIS/HSIL or completed HSIL ToC need no further testing; those with LSIL/HSIL in the specimen or incomplete HSIL ToC need annual HPV testing until two negative results; AIS requires annual co-tests until two consecutive negative co-tests.
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 | 2025 clarification |
|---|---|
| HPV 16/18 detected, negative LBC, normal colposcopy | If repeat 12-month follow-up again shows HPV 16/18 with negative LBC, repeat HPV testing in another 12 months may be considered rather than immediate re-referral in selected patients |
| Transformation zone not visible / no lesion seen | Endocervical curettage may be considered by trained clinicians with appropriate equipment |
| No cytologic, colposcopic or histologic abnormality | Diagnostic excision of the transformation zone is not recommended |
| Some excisional treatment contexts | LEEP may be preferred to cone biopsy in some circumstances due to lower post-surgical complications |
The 2025 update clarified that re-referral can sometimes be deferred for persistent HPV16/18 with negative LBC and normal colposcopy, that ECC may be considered in selected cases, and that diagnostic excision is not recommended without 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
- A vaginal speculum examination is required to obtain a clinician-collected cervical sample and
visualise the cervix.
- After the patient is prepared and comfortable, begin the speculum examination by examining the external genitalia for any abnormalities, then:
- warm the speculum, and apply a small amount of water-based lubricant
- hold the speculum in your hand with the handle facing down, and the blades closed
- 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
- ask the patient if they are in any discomfort and encourage feedback throughout the procedure,
- 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).
- Once the cervix is visualised, inspect for the following features:
- colour, size, shape
- position
- abnormal areas (lesions)
- surface characteristics
- the transformation zone (squamocolumnar junction; where the endocervical canal lining meets the squamous epithelium) which may or may not be visible
- discharge
- 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.
- 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.
- The choice of device depends on the location of the transformation zone, which is influenced by the patient’s age and menopausal status.
- 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.
- Record the patient’s name, date of birth and ID number on the specimen vial and any other patient identifiers required by the laboratory.
- On the pathology request form, note the following:
- Patient information.
- Cervical screening history and other relevant medical history (including gynaecological history).
- Any cervical abnormalities visualised during the cervical examination.
- Clearly indicate that the sample was clinician-collected.
- Patient’s Aboriginal and/or Torres Strait Islander status.
- 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
- Vaginal discharge.
- 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.