Indication - Cancer
Papanicolaou (Pap) smear test
Microscopic examination of cervical cells on slides
First added in 2019
Changed in 2020
Aid to diagnosis, Screening
To screen for and to aid in early diagnosis of cervical cancer
Cervical smear from liquid cytology specimen
WHO prequalified or recommended products
WHO supporting documents
Guidelines for screening and treatment of precancerous lesion for cervical cancer prevention. WHO guidelines. (2013). https://apps.who.int/iris/handle/10665/94830 ; WHO guide for establishing a pathology laboratory in the context of cancer control. https://www.who.int/publications/i/item/guide-for-establishing-a-pathology-laboratory-in-the-context-of-cancer-control ; Comprehensive cervical cancer control. https://www.who.int/publications/i/item/978924154895 ; Global strategy to accelerate the elimination of cervical cancer as a public health problem. https://www.who.int/publications/i/item/9789240014107 ; Guide to cancer early diagnosis. https://www.who.int/publications/i/item/guide-to-cancer-early-diagnosis ; WHO technical guidance and specifications of medical devices for screening and treatment of precancerous lesions in the prevention of cervical cancer. https://apps.who.int/iris/handle/10665/331698
ICD11 code: 2C77.Z
Summary of evidence evaluation
The Group was aware of substantial evidence of reductions in cervical cancer mortality in countries in which Pap smear testing has been used. The Group also noted emerging evidence of the greater benefits of screening with HPV testing than with the Pap smear (8) but recognized that HPV testing may not be feasible in all settings.
Summary of SAGE IVD deliberations
There is strong evidence for the accuracy of Pap smear testing and the impact of screening programmes with this test on mortality and advanced cancer rates. It is unclear whether Pap smear testing can be used to triage women with HPV infection.
SAGE IVD recommendation
The SAGE IVD recommended inclusion of the Pap smear test on the EDL, noting that the test is already widely used and is an effective alternative to HPV screening.
Details of submission from 2020
Disease condition and impact on patients: Cervical cancer is the fourth most common cancer among women globally, with an estimated 570 000 new cases and 311 000 deaths in 2018 (1). It is predicted that the burden of cervical cancer will increase, reaching 460 000 related deaths by 2040, an increase of almost 50%; 90% of the deaths will occur in LMICs. Currently, most cases in LMICs are diagnosed at a late stage, as a result of delayed clinical presentation due to untimely referral of symptomatic patients to appropriate diagnosis and treatment, often as a consequence of disconnection between the continuum of care at primary health care level and fragmentation of health services at secondary and tertiary levels. The WHO Director-General has called for global action towards the elimination of cervical cancer by addressing multiple dimensions, including the social and economic consequences. The WHO goal is to reduce drastically the number of incident cases per year (elimination) through prevention (HPV vaccination), early detection, treatment of pre-invasive cancer and treatment of invasive cancer (1, 2). Does this test meet a medical need? The Pap smear is a conventional cytological test for detecting abnormal cervical cells. It has been in use in developed countries for many decades and has been responsible for reducing the number of cancer deaths due to cervical cancer by up to 80%. How this test is used: The test is performed by skilled health providers, including mid-level health workers such as trained midwives, general practitioners and gynaecologists. Pap smears are used for primary screening for cervical cancer and for triage after a positive HPV result to avoid overtreatment of cervical lesions. It is also used for follow-up after treatment of cervical lesions (3, 4).
Public health relevance
Prevalence: Cervical cancer is the fourth most frequent cancer in women, with an estimated 570 000 new cases in 2018, representing 7.5% of all female cancers. The prevalence in 2018 was 1.5 million patients. Socioeconomic impact: According to WHO, lower-income countries will have the greatest relative increase in the incidence of cervical cancer in the next 20 years, exacerbating the current disparity. Cervical cancer patients face financial constraints, particularly catastrophic health expenditure, for life-saving treatment. In a study in rural China, > 50% of patients had financial problems due to such expenditure, which was more pronounced among illiterate and rural populations (3). According to IARC, cervical cancer has a strong economic impact among women in Brazil, China, India, the Russian Federation and South Africa, amounting to US$ 1.6 billion annually in productivity losses, particularly in South Africa (4).
WHO or other clinical guidelines relevant to the test
WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention (5).
Evidence for clinical usefulness and impact
An analysis was conducted of 24 studies (27 publications) found in a literature review and five studies in a review by the US Preventive Services Task Force on screening for cervical cancer (6). An RCT in India showed that even a single lifetime screening test significantly decreased the risk of mortality from and incidence of advanced cervical cancer. Cytological screening was shown in a cohort study to significantly reduce the risk of a diagnosis of invasive cervical cancer. Pooled evidence from 12 case–control studies also indicated a significant protective effect of cytological screening. No conclusive evidence was found for establishing optimal ages for starting and stopping cervical screening or for the frequency of screening; however, the studies suggested substantial protective effects of screening among women aged ≥ 30 years and for intervals of ≤ 5 years. Training and re-training, from collection to specimen preparation, has been shown to ensure good-quality Pap smears, and a “role delegation” model has been proposed for collection of specimens by community workers, specialized nurses, general practitioners in some settings and midwives, for reliable reproducibility and performance. The procedure is easy to learn and is considered to be a basic skill for gynaecologists and obstetricians.
Evidence for economic impact and/or cost–effectiveness
A microsimulation economic model was used to compare the cost–effectiveness of recommended screening policies for cervical cancer in high-income countries (7). The authors found that 15 of the policies were efficient from the point of view of life-years gained for lower costs. For 2–40 total scheduled examinations, the age range increased gradually from 40–52 years to 20–80 years as the screening interval decreased from 12 to 1.5 years. The predicted gain in life expectancy ranged from 11.6 to 32.4 days, with a gain of 46 days if cervical cancer mortality were eliminated entirely. The average cost–effectiveness increased from US$ 6700 for the longest screening interval to US$ 23 900 per life-year gained. In some countries, the recommended screening policies were close to efficient, but the cost–effectiveness could be improved by reducing the number of scheduled examinations, starting them at later ages or lengthening the screening interval. Preparation of specimens requires physicians or trained non-physician mid-level health workers. Reading of Pap smear tests requires a pathologist or technical staff trained in cytopathology.
Ethical issues, equity and human rights issues
Consent is required to obtain a cervical tissue sample. Counselling should be provided to all women undergoing cervical cancer screening (1). Pap smears are widely used for cervical cancer screening, and increased participation rates in screening and early treatment of precancerous lesions have been proven to reduce cervical cancer incidence, which is generally higher in vulnerable populations, including lower socioeconomic groups and women who are HIV-positive.
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clinicians. 2018;68(6):394–424. 2. Cancer. Geneva: World Health Organization; 2019 (http://www.who.int/news-room/fact-sheets/ detail/cancer). 3. Thapa N, Maharjan M, Xiong Y, Jiang D, Nguyen TP, Petrini MA, et al. Impact of cervical cancer on quality of life of women in Hubei, China. Sci Rep. 2018;8(1):11993. 4. Pearce A, Sharp L, Hanly P, Barchuk A, Bray F, de Camargo Cancela M, et al. Productivity losses due to premature mortality from cancer in Brazil, Russia, India, China, and South Africa (BRICS): a population-based comparison. Cancer Epidemiol. 2018;53:27–34. 5. WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. Geneva: World Health Organization; 2013. 6. Peirson L, Fitzpatrick-Lewis D, Ciliska D, Warren R. Screening for cervical cancer: a systematic review and metaanalysis. Syst Rev. 2013;2:35. 7. Van den Akker-van Marle ME, van Ballegooijen M, van Oortmarssen GJ, Boer R, Habbema JDF. Cost effectiveness of cervical cancer screening: comparison of screening policies. JNCI. 2002;94(3):193–204. 8. Koliopoulos G, Nyaga VN, Santesso N, Bryant A, Martin‐Hirsch PPL, Mustafa RA, et al. Cytology versus HPV testing for cervical cancer screening in the general population. Cochrane Database Syst Rev. 2017;(8):CD008587.