Cervical screening

The benefits of screening¹

Cervical cancer is the third or fourth most common female malignancy worldwide. It occurs much more frequently in developing countries.

In females in the UK, cervical cancer is the 14th most common cancer. It is the 19th most common cause of cancer death and accounts for 1% of all cancer deaths in females in the UK².

In 2014 there were 31,829 new registrations of cervical intraepithelial neoplasia 3 (CIN 3) in the UK. Most of these (54%) were in women younger than 30 years of age.

It has been estimated that the lifetime risk in the UK of developing cervical cancer is 1 in 135. Cervical cancer accounts for 8% of cancers diagnosed in women worldwide.

Around 50-79% of sexually active women have a lifetime risk of being infected with human papillomavirus (HPV). Almost 40% of women are infected with HPV within two years of first sexual activity.

The prevalence of HPV is extremely low (5%) in girls younger than 14 years of age, but rises in the mid-teens until the mid-20s where prevalence is 40% in those aged 20-24 years. Thereafter it declines. The most common infection is with type 16 (12%) which is oncogenic. Being seropositive for types 6, 11, and 18 is associated with being seropositive for type 16. The prevalence of high-risk HPV is 16%.

Coverage of the programme³

Cervical screening is available to women and people with a cervix aged 25-64 in England. For information about screening programmes in Scotland, Wales and Northern Ireland, see the Further Reading links at the end of this article.

All eligible people who are registered with a GP (as female) automatically receive an invitation by mail. Trans men (assigned female at birth) do not receive invitations if registered as male with their GP, but are still entitled to screening if they have a cervix.

For those eligible for screening, the first invitation is sent at the age of 24.5 years. People aged 25-49 receive invitations every three years. People aged 50-64 receive invitations every five years. Cervical screening is not recommended for anyone under 25 years of age who has not been invited.

The HPV vaccination programme started in 2008. Vaccinated individuals are still included in cervical screening programme, as the vaccine does not protect against all subtypes of HPV.

Cervical screening looks for the HPV which can cause abnormal cells on the cervix. Cervical screening samples are tested for types of HPV that can cause cervical cancer. If HPV is found, a cytology test is used to check for any abnormal cells. Individuals who do have HPV will have cytology triage carried out on the same sample. This is to see if HPV has caused abnormal cell changes.

Testing for HPV first, rather than looking at the cells using a microscope (cytology), is proven to be a more sensitive and more accurate test⁴. It will help to find more women with cervical cell abnormalities that may need treatment. HPV testing therefore helps to prevent more cases of cervical cancer.

If HPV is found but there are no abnormal cells, a follow-up screen is arranged for 12 months' time. This will check to see if the immune system has cleared the virus.

Most HPV infections are transient, and slightly abnormal cells often go away on their own when the virus clears. If HPV persists, abnormal cells can, if left untreated, turn into cancer over time.

If abnormal cells are found then refer for colposcopy.

If HPV is not found, a further screening test is offered in 3 to 5 years (depending on age).

The screening process³

A speculum made from disposable plastic (or from metal, which should be warmed) should be inserted vaginally to view the squamocolumnar junction of the cervix. Liquid-based cytology (LBC) is now the method of choice⁵. A brush is used rather than a spatula, which is rotated against the squamocolumnar junction (usually in the cervical canal). Two systems for LBC are in use. Both systems use brushes which look similar. In one, the head of the brush that contains the cells is broken off into a pot that contains special preservative liquid. The brush head is sent to the laboratory in the pot (this is the SurePath® brand method). In the other system, the brush is rinsed in the preservative to wash the cells into the pot. The brush is then discarded (this is the ThinPrep® brand).

LBC is now used nationally. It has significantly reduced numbers of inadequate smears, as the liquid is spun and treated to remove other cells such as pus or blood. Numbers of inadequate smears dropped from over 9% to 2.8% when LBC was introduced⁶. As a result, fewer repeats are needed, which benefits both women and laboratories. Reporting time is reduced and results are available and sent to the patient in approximately two weeks.

Older methods include the Papanicolaou (Pap) smear test which uses a brush or the Ayre spatula to sample the ectocervix, by rotating it twice through 360°. In both methods, the material obtained is smeared on to a microscope slide, which is then sprayed with or immersed in a fixative solution prior to transporting to the laboratory.

Interpreting smear results

If the test for HPV is negative then no further analysis is required.

If the test for HPV is positive, the cells are analysed to look for abnormalities in the appearance of the nucleus and other aspects of cell morphology (dyskaryosis):

• Inadequate - this may be because the cervical sample:

  • Was taken but the cervix was not fully visualised.

  • Was taken in an inappropriate manner (for example, using an unapproved device).

  • Contains insufficient cells.

  • Contains an obscuring element (for example, lubricant, inflammation or blood).

  • Is incorrectly labelled.

• Negative - no abnormality is detected.

• Abnormal - the cervical samples may show:

  • Borderline changes in squamous or endocervical cells. Cells are seen with abnormal nuclei, but the pathologist cannot say for certain that they are indicative of dyskaryosis. Many patients revert to normal smears eventually. Very few of these patients go on to develop cancer.

  • Low-grade dyskaryosis. Again, many women with this finding eventually revert to normal smears. Strictly speaking, the CIN grading system should not be used on smears but on cervical biopsy material obtained during colposcopy. However, mild dyskaryosis usually equates to CIN 1. Cancer is very unlikely.

  • High-grade dyskaryosis (moderate). This usually equates to CIN 2 and is seen in approximately 1% of samples. CIN 2 is considered a pre-cancerous condition with an intermediate probability of developing into cancer.

  • High-grade dyskaryosis (severe). This usually equates to CIN 3. It is at the higher risk end of the cancer spectrum. Fewer than 0.1% of smears will show nuclear and other cellular changes suggestive of carcinoma, sometimes referred to as carcinoma in situ.

  • Invasive squamous cell carcinoma.

  • Glandular neoplasia. Occasionally, abnormalities of glandular cells are seen, suggestive of adenocarcinoma in situ, adenocarcinoma of the cervix, endometrial adenocarcinoma or adenocarcinoma of an organ outside the uterus.

Management of results⁷⁸

Normal cervical cytology result

• If positive for high-risk HPV and negative cytology report: HPV test repeated at 12 months.

• If HPV-negative at 12 months: return to routine recall.

• If remaining high-risk HPV-positive, and cytology negative at 12 months: repeat HPV test in a further 12 months.

• If becoming high-risk HPV-negative at 24 months: return to routine recall.

• If remaining high-risk HPV-positive, cytology negative or inadequate at 24 months: refer to colposcopy.

• If remaining high-risk HPV-positive with cytology reported as borderline dyskaryosis or worse at 12 or 24 months: refer to colposcopy.

Abnormal cervical cytology result

Positive for high-risk HPV and abnormal cytology: refer to colposcopy.

Results are unavailable or the cervical cytology sample is inadequate

If the high-risk HPV test result is unavailable or cytology is inadequate at any screening episode: a sample is repeated in no less than three months.

If there is inadequate cytology at the 24-month repeat test: refer to colposcopy.

Referral times to colposcopy

• Possible invasion, high-grade dyskaryosis (moderate or severe), possible glandular neoplasia, borderline changes in endocervical cells: must be referred on a two-week wait pathway.

• Low-grade dyskaryosis, borderline changes in squamous cells, persistent high-risk HPV-positive cytology negative, or persistent inadequate samples, are referred in line with the 18-week pathway.