Cervical Cancer Screening

Cervical cancer screening tests women without symptoms for cervical pre-cancer and early cancer, using cervical cytology (the Papanicolaou or Pap test), testing for high-risk human papillomavirus (HPV), or a combination of the two. Because invasive cervical cancer is preceded by a long, detectable precancerous phase, screening followed by treatment of precursor lesions can prevent cancer rather than merely detect it earlier.

Definition

Cervical cancer screening is the application of cervical cytology and/or high-risk HPV testing to asymptomatic individuals with a cervix to detect precancerous lesions or early invasive disease for further evaluation.

Scope

This topic covers the rationale for cervical screening grounded in HPV as the necessary cause of cervical cancer, the cytologic and molecular tests used, and the way evidence and guidelines characterize their performance and intervals. It is a reference description of the screening approach; it is not individual screening advice and contains no management instructions.

Core questions

• How does detecting and treating HPV-related precursor lesions prevent invasive cervical cancer?
• How do cytology-based and HPV-based screening compare in their ability to prevent invasive disease?
• How do test choice and screening interval balance detection against the harms of over-referral?

Key concepts

• Human papillomavirus (HPV) as a necessary cause
• Cervical intraepithelial neoplasia (precursor lesions)
• Papanicolaou (cytology) test
• High-risk HPV testing
• Co-testing and primary HPV screening
• Colposcopy referral
• Screening interval

Mechanisms

Persistent infection with high-risk types of human papillomavirus is the necessary cause of essentially all cervical cancer (Muñoz, 2003). Such infection can drive normal cervical epithelium through graded precancerous changes (cervical intraepithelial neoplasia) over years before invasion occurs. Screening interrupts this sequence in two ways: cytology detects abnormal cells shed from these lesions, while HPV testing detects the causal infection directly. Individuals with abnormal results are referred for colposcopy and, where indicated, treatment of the precursor, removing the lesion before it can become invasive. Because HPV testing detects the underlying cause with high sensitivity, HPV-based screening has been shown to prevent more invasive cancers than cytology alone in randomized follow-up (Ronco, 2014).

Clinical relevance

Cervical screening is a long-established primary-care preventive activity, and guideline bodies describe age ranges, test modalities and intervals for average-risk individuals (Saslow, 2012; USPSTF, 2018). This entry summarizes that evidence base for reference; it is not a recommendation for any individual and does not specify who should be screened or treated.

Epidemiology

Where organized cytology-based programmes have been sustained, the incidence of and mortality from cervical cancer have fallen substantially over decades, and the disease remains far more common in regions without effective screening. Randomized European trials with extended follow-up showed that HPV-based screening conferred greater protection against invasive cervical cancer than cytology, supporting the shift of many programmes toward primary HPV testing (Ronco, 2014).

History

George Papanicolaou's mid-twentieth-century work on exfoliative cytology gave rise to the Pap test, which underpinned the first large-scale cervical screening programmes and major declines in cervical cancer. Harald zur Hausen's identification of HPV in cervical cancer, and the subsequent epidemiologic confirmation that high-risk HPV types are the necessary cause (Muñoz, 2003), reframed both prevention and screening, leading to HPV-based tests and, in randomized trials, evidence of their superior protection against invasive disease (Ronco, 2014).

Debates

Primary HPV testing versus cytology or co-testing

HPV-based screening detects more precursor disease and prevents more invasive cancers than cytology but yields more positive results that require triage; programmes differ in whether they use primary HPV testing, cytology, or co-testing, and at what starting age, reflecting trade-offs between sensitivity and over-referral.

Key figures

• George Papanicolaou
• Harald zur Hausen
• Nubia Muñoz
• Guglielmo Ronco

Seminal works

• munoz-2003
• ronco-2014

Frequently asked questions

Why can cervical screening prevent cancer rather than only find it early?

Cervical cancer is preceded by a long precancerous phase; finding and treating those precursor lesions removes them before they can progress to invasive cancer, so screening can prevent the cancer from developing.

What is the difference between a Pap test and an HPV test?

A Pap test examines cervical cells under the microscope for abnormal changes, whereas an HPV test detects the high-risk virus that causes those changes; some programmes use one, the other, or both together.