Cervical Screening

Introduction

The NHS cervical screening programme aims to detect and treat pre-cancerous cervical changes before they progress to invasive cancer, and is one of the most successful cancer prevention programmes in the UK, substantially reducing both the incidence of and mortality from cervical cancer since its introduction.¹

The programme changed fundamentally when it moved from cytology-first (examining cells under a microscope for abnormality) to primary high-risk HPV (hrHPV) testing. This reflects the understanding that persistent infection with high-risk HPV types is the necessary cause of essentially all cervical cancer, so testing for the virus itself is more sensitive at identifying women at risk than looking for the downstream cellular changes it may or may not have caused yet.²

The screening schedule

Screening is not offered to those under 25, as cervical cancer is rare in this age group and cervical changes are often transient, reflecting a young cervix's high rate of physiological HPV clearance; screening at this age has historically led to over-investigation and overtreatment without a clear mortality benefit.

The HPV-primary screening pathway

A sample is taken from the cervix (via a speculum examination, using a small brush) and first tested for high-risk HPV types. What happens next depends on this result.³

HPV negative

The sample is not examined further - cytology is not performed at all if hrHPV is negative, since without high-risk HPV, the risk of significant cervical dysplasia in the interval before the next screen is very low. The woman returns to routine recall (3 or 5 years depending on age).

HPV positive

The same sample is then examined by cytology ('reflex cytology') to look for cellular abnormality.

• HPV positive, cytology normal: repeat the HPV test in 12 months to check whether the virus has been cleared. If still HPV positive at 12 months, cytology is repeated; if still HPV positive at 24 months, refer to colposcopy regardless of cytology result
• HPV positive, cytology abnormal (any grade): refer directly to colposcopy

Inadequate samples

If a sample is inadequate (insufficient cells, or a technical failure of the HPV assay), it is repeated no sooner than 3 months later, to allow the cervical epithelium to regenerate and avoid a second inadequate result. If three consecutive samples are inadequate, the woman is referred for colposcopy rather than being sampled repeatedly.

Colposcopy

Colposcopy is direct visualisation of the cervix using a magnifying instrument (colposcope), allowing targeted assessment of abnormal areas.⁴

• Acetic acid is applied, which causes abnormal (dysplastic) areas to turn white ('acetowhite') due to their higher nuclear-to-cytoplasmic ratio and protein content
• Iodine (Schiller's test) may also be applied - normal glycogen-containing squamous epithelium stains brown, while abnormal or columnar epithelium does not take up the stain
• Punch biopsy of any abnormal area provides histological confirmation and grading
• Treatment (e.g. large loop excision of the transformation zone, LLETZ) can sometimes be performed in the same visit ('see and treat') if the abnormality is clearly high-grade

Cervical intraepithelial neoplasia (CIN)

CIN is the histological (biopsy-based) grading of dysplasia, distinct from the cytological terms used to describe the appearance of cells on a smear sample. This distinction - cytology describes what is seen on the sample, histology (CIN) describes what is confirmed on biopsy - is frequently a point of confusion.⁴

LLETZ (large loop excision of the transformation zone) is the most common treatment, performed under local anaesthetic in an outpatient colposcopy clinic, removing the affected transformation zone with a thin wire loop and electrical current. It is both diagnostic (the excised tissue is sent for histology) and therapeutic.

LLETZ is associated with a small increased risk of preterm birth and preterm prelabour rupture of membranes in subsequent pregnancies, related to the depth and volume of cervix removed. This does not outweigh the benefit of treating high-grade disease, but it is a relevant counselling point in younger women and a reason repeated or unnecessarily deep excision is avoided.

Test of cure

Women treated for CIN are invited for a test of cure at 6 months after treatment - an HPV test taken in the community. If this is HPV negative, the woman returns to routine recall (regardless of the CIN grade treated), reflecting how strongly HPV clearance predicts durable cure. If it is HPV positive, she is referred back to colposcopy. This is a notable simplification compared with the old cytology-based follow-up, which required years of annual smears.

HPV vaccination and its relationship to screening

The UK HPV vaccination programme, offered to adolescents (historically girls, now also boys) before likely sexual debut, protects against the high-risk HPV types responsible for the majority of cervical cancers, alongside other HPV-related cancers and genital warts.⁵

Exceptions to the standard pathway

• Pregnancy: screening is usually deferred until around 12 weeks postpartum unless the woman is overdue or has had a previous abnormal result, as pregnancy changes make the cervix more vascular and can complicate interpretation and sampling
• Symptomatic women: postcoital, intermenstrual or persistent abnormal bleeding should prompt clinical assessment and appropriate referral regardless of screening history or result - screening is for asymptomatic women, and symptoms should never simply wait for the next routine screen
• Women with HIV: screened annually rather than on the standard interval, given a higher risk of HPV persistence and progression
• Total hysterectomy for benign disease with no history of CIN: screening can usually stop, though this is individualised; if the hysterectomy was for cervical cancer or high-grade CIN, vault cytology follow-up may still be needed
• Women who have never been sexually active: can choose to opt out, as their risk is very low, though this should be an informed personal decision rather than an automatic exclusion

Prognosis

The screening programme, combined with HPV vaccination, has driven a substantial and ongoing decline in cervical cancer incidence in the UK, and modelling suggests cervical cancer could become a rare disease within coming decades in vaccinated cohorts. Uptake remains an important determinant of programme effectiveness at an individual level - encouraging attendance, addressing barriers to screening, and correcting misconceptions (particularly around HPV-primary testing and vaccination not replacing screening) all matter as much as the technical pathway itself.