Chapter 98: Cervical cancer screening

Cervical cancer

Cervical cancer is the fourth most common cause of cancer death in women worldwide, especially in developing countries.¹ It is the most common cancer in women in Eastern and Middle Africa, and the 14th most common in Australian women.^1,2 Australia has the second lowest incidence of cervical cancer in the world as a result of the success of the National Cervical Screening Program introduced in 1991, which has halved its incidence.³

The most common cervical cancer is squamous cell carcinoma (SCC), accounting for 80% of cases. Adenocarcinoma is less common and more difficult to diagnose because it starts higher in the cervix. Cervical cancer almost exclusively occurs in women who have been sexually active, due to exposure to human papillomavirus (HPV). Other risk factors include smoking, use of combined oral contraception >5 years, immunosuppression and exposure to diethylstilboestrol in utero.⁴

Since the introduction of the human papillomavirus (HPV) vaccine in Australia in 2007, the incidence of low- and high-grade abnormalities has significantly reduced in vaccinated populations. Studies have revealed reductions as high as 45% for low-grade abnormalities and 85% for high-grade abnormalities.⁵ Recent modelling suggests that, with the tools available, elimination of cervical cancer in local populations is achievable within our lifetime.⁶

It is now well established that the primary cause of cervical cancer is human papillomavirus. There are approximately 200 different types of HPV, 40–50 of which specifically infect the anogenital area. These types are mainly spread by skin contact during sexual activity.

Of the genital HPV types, 15 are classified as ‘high risk’, as they are associated with anogenital cancer (including squamous and adenocarcinoma of the cervix). HPV 16 and 18 are responsible for around 70% of invasive cervical cancers and 50% of high-grade lesions.

Prior to immunisation, infection with HPV was common and mostly transient, with 80% of women being infected with at least one genital type of HPV in their lifetime without ever knowing it. Cervical cancer is a rare outcome of HPV infection. Most cervical HPV infections are cleared or suppressed by cell-mediated immunity within 1–2 years of exposure. Persistent infection of the cervix with a high-risk HPV is known to cause high-grade cervical changes that, if left untreated, can progress to cervical cancer. More than 99.7% of cervical cancers test positive for HPV DNA.⁸

Basic pathology

The focus of attention is the transformation zone (see FIG. 98.1), where columnar cells lining the endocervical canal undergo metaplasia to squamous cells in the region of the squamocolumnar junction. It is important clinically to realise that this transformation zone can extend with progressive metaplasia of columnar epithelium and so the squamocolumnar junction may recede into the endocervical canal. This is a feature in postmenopausal women (see FIG. 98.2). As squamous cell carcinoma almost always arises in the transformation zone, it is vital that cells from this area are sampled.

HPV and the natural history of cervical neoplasia⁹

Low-grade squamous intraepithelial lesions (LSILs) represent an acute HPV infection of the transformation zone. LSILs are seen with both low- and high-risk HPV types. Most women will clear the virus over about 10 months with no lasting effect. Persistent infection with an oncogenic HPV type causes precancerous changes (high-grade squamous–intraepithelial lesion or HSIL).

HSILs may return to normal, persist or eventually progress to invasive cervical cancer. The average duration between HSILs and cancer is between 10 and 15 years. However, women with histologically confirmed moderate to severe dysplasia require a colposcopic assessment. FIGURE 98.3 and TABLE 98.1 illustrate the disease spectrum of cervical neoplasia.

Clinical presentation

Many patients with cervical cancer are asymptomatic and when early symptoms do arise they are often dismissed as of little consequence.

Symptoms, if present, may be:

• irregular vaginal bleeding, especially postcoital or intermenstrual bleeding

• postmenopausal bleeding

• vaginal discharge

• symptoms of advanced disease (e.g. back pain, fatigue, vaginal fistula)

Cervical screening test¹⁰

In December 2017, the National Cervical Screening Program changed from the two-yearly Papanicolaou smear (or Pap test) to a five-yearly cervical screening test. The cervical screening test uses a primary HPV test with partial genotyping. This test will separately identify oncogenic HPV types 16 and 18, and 12 other oncogenic HPV types (not 16/18). All women who have oncogenic HPV types detected will have ‘reflex’ liquid-based cytology (LBC) performed on the cervical sample, to guide further management.

Who should be screened?⁴

• Women are invited to commence cervical screening at 25 years (or two years after first sexual intercourse, whichever is later).

• Both HPV-vaccinated and non-vaccinated women should be screened.

• An exit test can be performed at age 70–74 years.

• Women aged 75 years or older may request screening.

• Screening applies only to asymptomatic women. Women with postcoital or persistent intermenstrual bleeding require a co-test (both HPV test and diagnostic LBC), and referral for an appropriate investigation to exclude malignancy should be considered.¹⁰

• For women who experienced first sexual activity at a young age (<14 years) and who had not received the HPV vaccine before sexual debut, a single HPV test between 20 and 24 years of age could be considered on an individual basis.¹⁰

Screening in particular groups¹⁰

Hysterectomy. Cervical screening is still required if the cervix was not completely removed. Vaginal vault co-tests (HPV and LBC) may be indicated if there is a history of gynaecological dysplasia or malignancy.

Pregnancy. Cervical screening can be safely performed at any time during pregnancy, provided that the correct sampling equipment is used. An endocervical brush or Cervex-Brush Combi should not be inserted into the cervical canal because of the risk of associated bleeding, which may distress the patient.

Postmenopausal women. Postmenopausal women may benefit from a short course of topical vaginal oestrogen before their cervical screening test. This may improve the quality of the test and comfort of the examination. Treatment should be stopped approximately 3 days before the test to ensure it does not interfere with the test interpretation.

Immune-deficient women. Woman with HIV or who are solid organ transplant recipients should be screened every 3 years with HPV testing.

Exposure to diethylstilboestrol (DES) in utero. An annual co-test (HPV and LBC) and colposcopic examination of both the cervix and vagina should be offered indefinitely.

Women with abnormal vaginal bleeding. A co-test is indicated and should not be delayed due to the presence of blood. Women with postcoital bleeding or persistent and/or unexplained intermenstrual bleeding require referral for colposcopy regardless of the result. However, premenopausal women who have a single episode of postcoital bleeding, a clinically normal cervix and negative co-test do not need to be referred for colposcopy. Postmenopausal women with any vaginal bleeding should be referred for a specialist gynaecological assessment to exclude genital tract malignancy.

Underscreened populations⁸

Special attention should be focused on screening the following women:

• Aboriginal and Torres Strait Islander women (mortality of cervical cancer five times that of other women in Australia)

• Women from culturally and linguistically diverse backgrounds

• Women in rural and remote areas

• Women with disabilities

• Women who have experienced sexual trauma and/or domestic violence

• Those who identify as lesbian, gay, bisexual, transgender, queer or questioning and intersex (LGBTQI)

The Cervical Screening Test consultation provides an excellent opportunity to perform a general women’s health check. For women of reproductive age, it is important to take a focused menstrual history, specifically enquiring about intermenstrual or postcoital bleeding. Consider discussing contraception use and the need for STI screening, especially for women aged under 30 years. Opportunistic discussions regarding family planning, breast awareness and breast screening are often appropriate.

Enquire about previous cervical screening results and whether the woman has found cervical screening difficult. Some women may be highly anxious, and identifying this early allows the clinician to address fears sensitively and discuss strategies that may help them feel more comfortable. Women with atrophic vaginitis often benefit from topical oestrogen in the immediate weeks prior to cervical screening.

Clinician-collected samples

The optimal cervical screening test contains:

• sufficient mature and metaplastic squamous cells to indicate adequate sampling from the whole of the transformation zone

• sufficient endocervical cells to indicate that the upper limit of the transformation zone was sampled; and to provide a sample for screening of adenocarcinoma and its precursors

Optimal timing of specimens

• Avoid performing a cervical screening test during menstruation.

• Avoid in the presence of obvious vaginal infection.

• Avoid within 48 hours of use of vaginal creams or pessaries or douching.

Communicating with the pathologist

Good communication with the pathologist is essential. It is important to provide basic details and the clinical history on the pathology form sent to the laboratory. It is especially important to include whether the patient is symptomatic, as this changes the testing procedure. Include the patient’s age, current hormonal state, such as pregnancy, the postpartum period or if they are postmenopausal, the presence of an IUD, previous abnormal results and clinical findings.

The method

1. Explanation and history

   Take time to explain the reason for the cervical screening test, especially if it is the first. Anatomical models are useful in describing the procedure.

   Explain that it usually does not take long, that it may be uncomfortable but should not be painful.

   Slow, deep breathing often helps relax the pelvic floor, allowing for easier speculum insertion.

   Take a brief history as previously outlined, enquire about previous cervical screening results (if any), as well as direct questions about any intermenstrual or postcoital bleeding. Verbal consent should be obtained.⁵

   Encourage the woman to empty her bladder if she desires and ensure privacy before asking her to undress below the waist. A gown or cover sheet should be provided.

   Check if the woman would like a chaperone to be present during the examination.

2. Equipment⁶

   Wash hands and prepare the following equipment:

   • adequate light source

   • appropriate-sized speculum (small for women having a first test, wider for women with poor vaginal tone)

   • water-based lubricant if using a plastic speculum

   • non-sterile gloves for both hands

   • vial of liquid medium

   • swabs for STI screening if required

   • cervical screening implements; choose from:

     • – cervical sampler broom

     • – endocervical brush

     • – Cervex-Brush Combi

     • – spatula

     (refer to FIGURE 98.2 for recommended choice)

     Special notes:

   • pregnancy—avoid use of the endocervical brush and the Cervex-Brush Combi

   • eversion—take care to sample the squamocolumnar junction

3. Positioning

   The supine position is usually best (see FIG. 98.4). The left lateral position can be used if smears are difficult to obtain (e.g. older women with lax anterior vaginal walls, older women with poor hip mobility). The Sims exaggerated left lateral position (see FIG. 98.5) provides better exposure of the vulva but requires more manipulation of the patient. Better visualisation of the cervix is obtained if the patient elevates her buttocks with her fists, a small pillow or towel.

4. Inspection of external genitalia

   Observe any skin conditions or lesions, any intraoital bleeding or vaginal discharge.

5. Inserting the speculum

   A metal speculum should be warmed with lukewarm water. A small amount of water-based lubricant is appropriate for a plastic speculum. Gently spread the labia with a gloved hand and introduce the speculum with the blades remaining horizontal and closed. Gently advance the speculum into the vagina guided by the posterior wall. Open the blades of the speculum slightly to guide the visual location of the cervix. Remember that the cervix is situated in the upper sixth of the anterior vaginal wall (not in the apex of the vagina).

6. Visualising the cervix

   When the cervix is visualised, lock the blades to keep the speculum in position. Good lighting and exposure of the cervix is essential. Note any significant features or abnormalities of the cervix. A cervical ectropion is normal in most premenopausal women.

7. Taking the sample

   There are a variety of sampling instruments to choose from.

   Cervical sampler broom: can be used alone if the transformation zone is visible. Insert the central part of the brush into the os and rotate for 3–5 turns (FIG. 98.6A).

   Spatula: take care to keep contact with the ecto-cervix and rotate once or twice. Use with the endocervical brush to maximise endocervical sampling.

   Endocervical brush should be advanced until only the lower bristles are still visible, then rotated for a quarter of a rotation (see FIG. 98.6B). The endocervical brush should be avoided in pregnant women as it tends to cause bleeding.

   Cervex-Brush Combi combines features of the cervical broom and endocervical brush. Insert the central part of the brush into the os and rotate for two turns. It is not advised in pregnancy.

   It is common practice to use either the cervical sample broom or spatula first, followed by the endocervical brush. Use of the Cervex-Brush Combi alone is an alternative.

   After removing the speculum, perform a bimanual pelvic examination if appropriate. A bimanual examination may assist in locating the cervix if it could not be visualised at the initial speculum examination.⁵

8. Transferring the sample

   Transfer the sample to the liquid medium as quickly as possible, swirling the device vigorously 10 times (see FIG. 98.6C). The cervical sample broom and Cervex-Brush Combi should hit the base, forcing the bristles apart (see FIG. 98.6D). Remove the device from the vial and ensure the cap is secured tightly (see FIG. 98.6E).

   Follow-up

   Discuss mutually suitable arrangements to ensure that the woman obtains the result of the test, whether it is positive or negative. Inform her when her next test is likely to be due (special cards are available) and have a system in place to send a reminder note.

   The explanation of the results and follow-up required, especially if there is an abnormality present, should be crystal-clear to the patient. Common medicolegal claims made against GPs include poor communication regarding cervical screening tests and failure to arrange adequate specialist referral for women with abnormal results or a clinically suspicious cervical lesion.

Management of results

Follow the guidelines in TABLE 98.2 and FIGURE 98.7 for management of results.

Post-treatment assessment of HSIL¹⁰

A woman treated for HSIL should complete a test of cure surveillance to confirm her treatment has been successful. Test of cure surveillance is a co-test (HPV and liquid-based cytology test) performed 12 months after treatment, and annually thereafter, until the patient receives a negative co-test on two consecutive occasions. She should then return to 5-yearly screening.

Data shows that more than 80% of women diagnosed with invasive cervical cancer have never been screened or were more than 6 months overdue for a screening test at the time of diagnosis. Providing HPV self-collection kits to never-screened and underscreened women has been shown to improve screening participation in international studies. HPV tests using self-collected samples are considered to have moderate-to-high sensitivity and comparably high specificity for detecting CIN2+.

Under the renewed National Cervical Screening Program, HPV testing on self-collected samples will be available to some women aged 30–74 years under the supervision of a health care professional who also offers cervical screening. The following groups of women will be eligible:

• women who have never participated in cervical screening and are aged 30 or over

• women who are overdue for cervical screening by 2 years or longer and are aged 30 years or over

Women should be advised that a clinician-collected sample is preferred because it is more effective and reflex LBC can be performed on the same sample. If the woman declines the clinician-collected sample, she will be able to submit a self-collected sample. Self-collection is nonetheless preferred compared to non-participation in cervical screening.

Self-collection will not be available to women who are pregnant, symptomatic, have undergone hysterectomy with a history of HSIL and women exposed to DES in utero.

If HPV (not 16/18) is detected on a self-collected sample, a clinician-collected liquid-based cytology is advised. If HPV 16 or 18 is detected, the patient should be referred directly for colposcopy and a cervical sample for LBC will be collected at that visit. Follow-up is otherwise the same as for clinician-collected samples.

At the time of writing, self-collection is not yet available as laboratories require validation of HPV analysers on self-collected swabs.

In 2007, Australia led the world with its national publicly funded HPV vaccination program, using a three-dose schedule of the quadrivalent HPV vaccine that protects against HPV types 16 and 18 (high risk for cervical cancer) and types 6 and 11 (which cause genital warts). Vaccination ideally occurs before first sexual activity. Currently, the HPV vaccine (Gardasil®) is administered through the National Immunisation Program to males and females aged 12–13 years. A 9-valent vaccine, with the capacity to prevent up to 90% of cervical cancers, is being considered for inclusion in the program.

Since 2007, reductions in the prevalence of HPV types 16 and 18, anogenital warts and histologically confirmed HSIL have already been documented in young women, including unvaccinated young women. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, 90% for genital warts, 45% for low-grade cytological cervical abnormalities and 85% for high-grade cervical abnormalities have been reported.⁵ Women who have been immunised still require cervical screening because the vaccine does not prevent all HPV types that cause cervical cancer.