Keywords

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Introduction

The WHO has outlined prerequisites necessary to determine if a mass screening programme should be developed [1]. These prerequisites include:

  1. 1.

    The disease must be common enough to justify mass screening

  2. 2.

    It must be associated with significant mortality

  3. 3.

    Effective treatment is available for pre-invasive or early invasive disease

  4. 4.

    Detection and treatment of a presymptomatic state result in benefits beyond those obtained through treatment of symptomatic disease

In this chapter, we will review the evidence available for each of these prerequisites as they pertain to cervical cancer [2].

Magnitude of the Problem

Globally, cervical cancer accounts for 10 % of all female cancers, making it the third leading cause of cancer and the fourth leading cause of cancer death in women [3]. Annually, 530,232 women are affected with cervical cancer (ASR 15.2), and 275,008 women die of their disease (ASR 7.8). The mortality to incidence ratio is 52 %. Eighty-five percent of cervical cancer cases occur in low-resource countries, and 85 % of these women die of their disease [4–8]. In low-resource settings, cervical cancer is the second leading cause of cancer and death compared to high-resource settings, where it is the tenth leading cause of cancer [3]. Age-standardized incidence rates are highest in Africa (i.e. ASR 69 per 100,000 in Tanzania), Central America (i.e. ASR 55 per 100,000 in Bolivia), south central and eastern Asia (i.e. ASR 24.6 per 100,000) and South America (i.e. ASR 23.9 per 100,000) [9]. These rates are astronomical when compared to rates of less than 6 per 100,000 in Australia/New Zealand, Europe, and North America [10]. These disparities in part are based on whether there is access to an organized screening programme [11]. Thus, in low-resource settings where such programmes are non-existent, women with cervical cancer often present to hospital with symptoms such as bleeding and foul smelling discharge, which reflect advanced/metastatic disease [12]. Thus, globally, cervical cancer is a common and deadly disease fulfilling the first and second prerequisites put forward by the WHO to justify mass screening.

Process of Cervical Cancer Development

Cervical cancer arises in the transformation zone of the uterine cervix. This area undergoes dynamic change especially at puberty where squamous epithelium impinges upon the glandular epithelium in a process known as metaplasia. The human papilloma viral infection is a very common sexually acquired infection that is introduced with the onset of sexual activity. In most cases, the viral infection is resolved by the woman’s own immune system. However, if there is a persistent infection, especially with the oncogenic types of HPV (i.e. 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 57, 58, 68, etc.), the viral oncoproteins produce loss of the cell cycle controls. The cells reflect this with a change in nuclear to cytoplasmic ration, loss of nuclear regularity, and chromatin clumping. These cytologic changes are known as dysplasia or, following a more contemporary nomenclature using the Bethesda terminology, squamous and/or adeno intraepithelial lesion (SIL) (see ref. [20]). The degree of cellular and architectural changes in the cervical biopsy is classified in terms of levels of cervical intraepithelial neoplasia (CIN). In the mildest form, CIN 1, the HPV infection causes changes in the lowest one-third of the epithelium. Often (80 %), a CIN 1 lesion will resolve over 12–24 months, especially in young women. However, in the most severe form, CIN 3, the cellular changes affect the whole epithelium above the basement membrane. The risk of a CIN 3 lesion progression to cancer is estimated to be 31.3 % (95 % CI 22.7–42.3) if the lesion is not detected and treated [13]. The peak incidence of an HPV infection occurs when a women is in her 20s. The peak incidence of CIN 3 is seen in her 30s [13, 14]. The peak incidence of cervical cancer is in the mid-40s [15]. This transition from infection to dysplasia (SIL or CIN) to cancer takes several years, thus allowing the opportunity for detection by a screening test.

In the case of cervical cancer, there is a presymptomatic/precancerous disease state that spans a significant period of time during which, if identified, there is the potential to remove the disease. This meets prerequisite 4 of the WHO criteria justifying mass screening (Table 6.1).

Table 6.1 Comparing Classification Systems for Squamous Lesions.
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Prevention as a Component of the Disease Continuum (Framework)

Cervical Screening should be part of a woman’s regular health journey, where asymptomatic women are assessed with a test to determine if a precancerous lesion is present. Then, if found, Cervical Diagnosis becomes part of the cervical cancer journey, where women with a positive screening test are sent for further diagnostic test(s). Further along that path, Cervical Treatment involves removing the disease to prevent the occurrence of cancer or identifying and treating asymptomatic early stage cancer (Fig. 6.1).

Fig. 6.1
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Prevention as part of the disease continuum. (Courtesy of Cancer Care Ontario, Toronto, Ontario, Canada)

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Definition of Low-, Medium-, and High-Resource Countries

There are many ways of defining “developing” or “low-resource countries.” Some agencies use a definition based on rate of literacy or life expectancy [16]. For this chapter, we will use the classification put forward by the World Bank. The Gross National Income per capita is divided into three strata: low-resource countries (US$ 1,005 or less), middle-resource (low-middle is US$ 1,006–3,975; upper-middle US$ 3,976–12,275), and high-resource countries (US$ 12,276 or more) [17].

The remainder of this chapter will focus in more detail on the WHO prerequisites 3 and 4 as they pertain to cervical cancer prevention.

Methods

For this chapter, we reviewed the literature on the screening modalities for cervical cancer in low-resource settings, and we included MEDLINE, CINAHL, EMBASE, GOOGLE, and the Cochrane library from 2000 to December 2011. Bibliographies of relevant review articles and included studies were scanned for additional relevant publications. Included in the literature search strategy were terms such as “cervical cancer,” “cervical neoplasm,” “utero-cervical neoplasm,” “screening,” “developing country,” “low-resource country,” “cervical cytology,” and “VIA testing” and “HPV testing.” We excluded non-English publications.

Screening Tests

What Makes a Good Screening Test?

For a screening test to be clinically useful, it must be simple, inexpensive, accurate, and acceptable by the patient. In this section, we will review the available screening tests, their efficacy, advantages, and limitations. There are three screening tests which will be reviewed: cervical cytology, visual inspection, and oncogenic HPV assessment. The best way to think about screening is as a therapeutic intervention. In this chapter, randomized trials examine the effect of screening on patient important outcomes. The outcomes of interest are that cervical cancer screening will (1) reduce the incidence of cervical cancer through detection and removal of precancerous lesions and (2) reduce disease progression through detection of invasive cancers in the early stages, thereby improving the chance for cure and reducing mortality [18]. See Table 6.2.

Table 6.2 Test parameters
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The possible consequences of screening are that some women will have a true-positive result (a) (i.e. HSIL) with clinically significant disease (CIN 3), and they will benefit from treatment. However there are some patients with inconsequential disease (ASCUS), and they may experience the consequences of labelling, investigation, and treatment for disease (HPV infection) which may never affect their lives. Women with a false-positive result (b) may be adversely affected by the risks associated with investigation (i.e. colposcopically directed biopsy). False Negative (c) involves women who, for example, have a normal Pap test when they actually have disease; this result delays investigations. Patients with a true negative (d) experience the benefit associated with accurate reassurance of being disease free, but they may have experienced inconvenience, cost, and anxiety associated with screening [19].

Cervical Cytology (Otherwise Known as the Pap Test or Pap Smear)

In 1940, George Papanicolaou discovered that cells retrieved from the apex of the vagina could reflect changes in the cervix that over time led to cervical cancer. Today, cervical cytology is obtained usually by a physician. After the woman is counselled about the purpose of the test and gives permission to have the test, she is examined in the lithotomy position. With a speculum in the vagina and either using either a spatula and/or a brush, cells are scraped from the cervix and either spread across a glass slide and fixed with cytospray (or hairspray in some jurisdictions) (Fig. 6.2). Alternatively the cells are placed in a liquid-based media (such as Hologic’s Thin Prep®, Bedford, MA), or BD SurePath™ (Franklin Lakes, NJ). This specimen is processed in a lab with various stains and read by a cytotechnologist and/or cytologist. The results are reported using the Bethesda 2001 classification system [20]. A few weeks after the test is obtained, the woman must return or call her physician’s office for her results and disposition planning.

Fig. 6.2
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Example of a cervical cytology specimen

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Efficacy

There has only been one randomized trial comparing a once-in-a-lifetime cervical cytology to no screening. Fifty-two villages in India, with a total of 131,746 healthy women aged 30–59 years, were randomly assigned to one of four groups [21]. These groups received screening by a single lifetime cervical cytology (n  =32,058), HPV test (n  =  34,126), visual inspection by acetic acid (n  =  34,074), or standard care which involved giving women information on how to seek screening at local hospitals (n  =  31,488). The single lifetime cytology test had no significant impact on 8 years mortality (age-adjusted HR 0.89, 95 % CI 0.62–1.28, p  =  0.53). The single lifetime cytology test had no statistical impact on 8 years incidence of cervical cancer (age-adjusted HR 1.34, 95 % CI 0.99–1.81, p  =  0.06). The higher incidence of cervical cancer in the screened group is explained by the active detection of disease in the screened group and the fact that this was the first screen almost any woman had received. A single lifetime cytology test had no statistical impact on 8-year incidence of Stage 2 or higher cervical cancer (age-adjusted HR 0.75, 95 % CI 0.51–1.10, p  =  0.14).

Although there is no direct evidence from randomized trials for the efficacy of a single cervical cytology test in decreasing rates of cervical cancer, there is overwhelming epidemiologic data to infer the impact of cytology screening on reducing cervical cancer rates. These data come from two types of work. First, case–control studies have been reported from many jurisdictions around the world comparing the history of cervical cytology of women with cervical cancer and age-matched controls of those without cervical cancer (i.e. Canada, Columbia, Costa Rica, Finland, Japan, Italy, South Africa, Panama, Sweden, USA). These studies show consistently that the odds of developing cervical cancer are lower in those women who received at least one Pap test (in the order of OR 0.036) compared to those not screened [18, 22–34]. The second body of epidemiologic evidence is the correlation of incidence and mortality trends of cervical cancer in screened populations such as reported from Canada, the Nordic countries, and the UK [35–38].

The test parameters for conventional cervical cytology to define lesions of CIN 2 or worse are sensitivity 44–78 % and specificity 91–96 % [39, 40]. The low sensitivity means that, in those women with a normal test, it must be repeated frequently (i.e. at least every 3 years) to ensure that a lesion has not been missed or that a new lesion has not developed [15]. The high specificity means that those women without disease will have a normal test result.

Advantages

The advantages of cervical cytology are that the test is easy to learn to perform and the consumables (i.e. spatula) are low cost.

Limitations

Since cervical cytology has been available for at least 50 years, its limitations are well documented:

  1. 1.

    As discussed earlier, a single Pap test has low sensitivity, and this sensitivity can be improved with repeated cytological assessments over time. The low sensitivity can be related to process issues: for example, the physician may fail to sample the squamocolumnar junction (more common in perimenopausal or postmenopausal women). This high false-negative rate is a serious weakness [41].

  2. 2.

    A high rate of unsatisfactory smears can occur: for example, if the sample is not fixed appropriately, if cotton tips applicators are used to retrieve the specimen (as the cotton fibres create artefact on the slide), or if the woman has an infection. If the woman has an unsatisfactory smear, she should return for a repeat test. Liquid-based cytology has been developed to decrease the amount of time necessary to assess each specimen, to decrease the number of unsatisfactory cervical cytology reports, and to allow the residual fluid to be available for HPV assessment; it can be automated. However, a systematic review and meta-analysis of liquid-based cytology show that sensitivity and specificity are the same as for conventional cytology [40].

  3. 3.

    Another limitation is that evaluation of the cytology test is highly subjective. The cytologists and cytotechnologists must be trained to recognize various cellular patterns. Thus, at the laboratory level, there must be an ongoing system of quality assurance both in optimally staining the slides and pattern recognition.

  4. 4.

    The cost of infrastructure, including laboratory space, personnel, and information networks, can be daunting. Conventional cytology screening is resilient and the reagents are low in cost, compared to those jurisdictions that use liquid-based cytology, which requires expensive equipment, a reliable electrical source, and daily maintenance, which may not be available in all settings [42, 43].

  5. 5.

    The attitudes and beliefs of a woman influence her willingness to have a screening test. For example, a pelvic exam may not be acceptable to all women, and this may be related, in part, to the gender of the provider.

  6. 6.

    Access to the test may be a limitation. In some settings, the test is accessible only through reproductive health clinics. Thus, peri- and menopausal women, who are at the highest risk for dysplasia, may not attend and so be disadvantaged.

  7. 7.

    A cytology-based system requires that a woman return to see the physician repeatedly (for the test, for test results, and subsequent tests, resulting in reduced patient compliance as discussed later in this chapter). Out-of-pocket costs for health care and indirect costs of lost hours of productive work, child care expenses, or long distance travel can put a great burden on poor women. Thus, a cytology-based system may fail due to low compliance [42, 44–48].

Other Considerations from Experiences in Low-Resource Settings

In Central and South America, there was a high coverage in screening appropriate women, but the quality of cytology assessment was poor, and so rates of cervical cancer remain high [49]. Strategies to improve this problem included implementing telemedicine systems to help bring high-quality cytology assessment to remote settings. For example, the Italian NGO Associazione Patologi Oltre Frontiera (APOF) has worked since 2000 to help countries in Sub-Saharan Africa [50]. A pilot project in Chirundu, Southern Zambia, showed that it was feasible to train histology lab workers to screen Pap smears, take digital photographs of suspicious or positive cases, and then by digital scanner and satellite connection confirm a diagnosis within four days. Original slides are reviewed in Italy every 6 months for quality-control purposes.

Conclusion

Cervical cytology, especially if repeated periodically during a woman’s lifetime, has resulted in a fall in cervical cancer rates; however, there are limitations not just with the test but the context in which it is applied. We will discuss these in more detail later in this chapter.

Visual Inspection (Otherwise Known as Direct Visual Inspection)

Visual inspection involves inspecting the cervix with the naked eye using a bright light source and is followed by the application of either a 3–5 % dilute acetic acid for one minute (known as visual inspection with acetic acid, VIA) or acetic acid test (AAT). If Lugol’s iodine is used, this is called visual inspection with Lugol’s iodine (VILI) or the Schiller’s test.

Visual Inspection with Acetic Acid

With the application of acetic acid to the cervix, there is a reversible coagulation of intracellular proteins. If dysplasia is present, a pronounced white lesion is seen. A VIA test can be reported as “negative” if no lesion is seen, “positive” if there is detection of a well-defined aceto-white area close to the squamocolumnar junction (Fig. 6.3), and “suspicious for cancer” if an irregularly exophytic or ulcerative lesion is identified (Fig. 6.4) [51, 52]. VIA can only reliably be used in women where the squamocolumnar junction is visible on the ectocervix; thus, it should mainly be used in women 30–45 years old.

Fig. 6.3
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Cervix after the application of 3-5 % vinegar showing a white lesion. This is an example of VIA positive

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Fig. 6.4
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Cervical cancer. This is an example of VIA suspicious for cancer

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Efficacy

A cluster-randomized trial in the Dindigul district of India involved 49,311 women aged 30–59 years. They were randomized to health education or VIA. At 7 years, the VIA group had a lower incidence of cancer (HR 0.75 95 % CI 0.55–0.95) and lower mortality (HR 0.65, 95 % CI 0.47–0.89) [53].

A cluster-randomized trial in India involved 142,701 women aged 30–59 years. One group was given education alone. The three other groups involved a once-in-a-life time cervical cytology or VIA or oncogenic HPV test. Detection of CIN 2/3 was the same for all three screening tests at 0.7 % for VIA, 1 % for cytology, and 0.9 % for oncogenic HPV DNA [21].

The test parameters for VIA have been critically assessed, and the sensitivity ranges from 49–96 % and the specificity ranges from 49–98 % [54, 55].

Advantages

VIA has several advantages. It is inexpensive [9, 56, 57]. When used in already existing health centres, the instruments required for VIA are already present, and there are few disposables [9, 56–59]. VIA is easy to learn [57] and can be performed by a wide range of health-care workers (i.e. physician, nurse, midwife, local health-care worker) [52, 56, 57, 60–63]. The accuracy of VIA is the same as cervical cytology. Sensitivity is the same or higher than cervical cytology. VIA provides immediate results, which can be given to the woman during the same physician visit [9, 56–59, 63, 64]. VIA can be used in a screen-and-treat algorithm which decreases issues related to compliance (to be discussed later in this chapter). VIA does not require a lab infrastructure [59]. VIA can be associated with increasing screening coverage, which in part means laying down the framework to integrate novel, more sensitive technologies in the future [65].

Limitations

In VIA the acetic acid can cause a temporary stinging sensation for the woman.VIA is not suitable for older women because the squamocolumnar junction is not visible on the exocervix [57, 58]. VIA is a subjective test with high inter-rater variability, so substantial provider-training and ongoing quality assurance assessments are needed [55, 66–70]. Some fear that the quality assurance of VIA may be more difficult to control than the quality of cervical cytology [71]. VIA has a lower specificity and higher false-positive rate, which means that women need to be referred for a second test like colposcopy to determine if the disease is truly present. This might mean the colposcopy and pathology departments could be overwhelmed [58]. If a second test is performed, the cost is increased [70]. In a see-and-treat scenario, if a second test is not performed, many women would be treated who do not have disease [72]. One of the problems with many of the studies is the lack of verification bias (i.e. the disease status of those who were test negative was not assessed) [21, 43, 54, 73–78]. Similarly, there is a correlation between visual screening tests and colposcopy, so it is possible that the sensitivity and specificity of VIA and VILI are overestimated [55].

Some barriers to VIA uptake include the resistance of medical professionals to using a screening test other than cervical cytology. Some national policies restrict screening and treatment to physician providers, and they do not recognize or support use of VIA, especially when done by midwives or nurses.

Other Considerations

VIA lends itself to mobile telemedicine technology. In Gaborone, Botswana, four nurse midwives collected VIA images by mobile phone, and these were transferred to a website by MMS without need for an Internet connection. Unfortunately, in this study in a third of cases the images were insufficient [56, 79]. The concept of VIA image capture was assessed in El Salvador. Here, a digital camera gave the opportunity for a second assessment which resulted in a higher sensitivity than using the naked eye alone [80]. Capturing the images can be useful for getting further input from colleagues or physician staff, medical record storage, or quality assurance.

Visual Inspection with Lugol’s Iodine

In visual inspection with Lugol’s iodine (VILI), the cervix is washed with Lugol’s iodine and the glycogenated cells of the vagina and cervix stain a deep mahogany brown. The non-glycogenated cells such as the glandular epithelium and areas of dysplasia do not stain. Findings are reported in terms of “VILI negative” (no lesion or abnormality), “VILI positive” (a lesion is identified) (Fig. 6.5), and “suspicious for cancer.”

Fig. 6.5
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Cervix after the application of Lugol’s iodine. This is an example of VILLI positive

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Efficacy

There are several studies assessing the use of VILI. A multi-centre study involving 49,000 women in India and Africa compared evaluations with VIA and VILI. The sensitivity of VILI was 92 % and the specificity was 85 % [64]. Another study involving 3,000 Latin-American women showed less optimistic findings, with sensitivity of 53 % and specificity of 78 % [81].

Advantages

VILI can be conducted by nurses or midwives after being trained. It requires minimal supplies (i.e. Lugol’s iodine). Results are available at the time of test.

Limitations

Lugol’s iodine is quite messy and can stain a person’s clothes. Providers require training and ongoing quality reviews as the assessment is subjective. There are no studies on the efficacy of VILI in decreasing the incidence or mortality from cervical cancer.

VIA with Magnification

The AviScope™ is one example of VIA with Magnification. Here, the cervix is inspected with LED illumination with four-fold magnification of the cervix [82].There are no reports on efficacy. The advantage is better identification of lesions. The limitations in low-resource settings are the occurrences of power outages, power fluctuations, and difficulty in repairing equipment or getting parts [83].

Oncogenic HPV Test

A persistent oncogenic HPV infection is the known cause of cervical dysplasia and, ultimately, cancer. The genital tract can be swabbed for oncogenic HPV. There are a number of commercially available tests available for assessing for the presence or absence of oncogenic HPV types (i.e. HC2, HPV, DNA test produced by Qiagen (Hilden, Germany), also called the Digene® HPV test) or specific oncogenic HPV types (i.e. cobas® HPV test by Roche Molecular Diagnositics (Pleasanton, CA)). The number of HPV types varies slightly across tests.

The global estimates are that the overall age-adjusted prevalence of HPV is 10.5 %. Geographic variation of oncogenic HPV prevalence exists with the higher rates being noted in resource-poor regions (i.e. 35 % in Mongolia) [84]. Prevalence is known to decline as a woman ages. Using an HPV test in women over 30 years of age is more likely to pick up persistent HPV infection associated with dysplasia compared to the transient infection seen in younger women.

Efficacy

The efficacy of a once-in-a-lifetime oncogenic HPV test was evaluated in fifty-two clusters of villages in India, with a total of 131,746 healthy women between the ages of 30 and 59 years [21]. The villages were randomly assigned to four groups: one group underwent screening by a once-in-a-lifetime HPV test (34,126 women), and one group received the standard of care which involved giving women information on how to seek screening at local hospitals (31,488). The once-in-a-lifetime screen made an impact on mortality. Screening using a single lifetime HPV test made a significant impact on 8-year mortality when compared to no screening (age-adjusted HR 0.52, 95 %CI 0.33–0.83, p  =  0.005). There was no impact on overall incidence of cervical cancer (age-adjusted HR 1.05, 95 % CI 0.77–1.43, p  =  0.76). However, a randomized study from Finland using cancer registry data showed in 58,076 women that HPV testing with cytology triage was superior to cytology alone in identifying CIN 3 or worse (HR 1.77, 95 %CI 1.16–2.74) [85]. The study from India showed that only HPV testing had an impact on the incidence of advanced cancer (Stage 2 or higher cancer), by significantly decreased advanced cervical cancer (age-adjusted HR 0.47, 95 %CI 0.32–0.69, p  =  0.0001) [35].

There have been six randomized controlled trials in Europe and one in Canada evaluating HPV test, either alone or in combination with cytology. HPV DNA is more sensitive than cytology in women over 30 years (96 % compared to 53 %) but less specific (91 % compared to 96 %) [86–88]. The very high negative predictive value of HPV testing allows prolongation of the interval between tests (i.e. the test need only be repeated every 5 or more years) [22, 49, 88].

Twenty-five cross-sectional studies where women were concomitantly tested with Pap test and HC 2 HPV test also showed that the sensitivity for CIN 2/3 was 89.7 % (95 %CI 86.4–93.0) [22, 38]. Specificity was 85–90 % [22]. Unfortunately, the HC2 HPV test has consistently high sensitivity in Europe and North America [89, 90] but not in all low- and middle-resource countries. For example, sensitivity of HC2 HPV test in three cross-sectional studies in India were 50, 70, and 80 %; Peru was 77 %; Zimbabwe was 81 %; Brazil was 83 %; and South Africa was 88 % [15]. A cross-sectional comparison of screening performance of five screening methods (VIA, VILI, VIA with magnification (VIAM), cytology, and HPV) in 11 study sites in low-resource settings showed the following results for the detection of CIN 2 or worse: cytology (sensitivity was 57 %, specificity 93 %), VIA (sensitivity 79 % and specificity 85 %), and HPV (sensitivity 62 % and specificity 94 %) [40, 90].

Through funds from the Bill and Melinda Gates Foundation (Washington State), an HPV test (careHPV™, Qiagen, Hilden, Germany) was specifically developed with the issues unique to low-resource countries in mind. careHPV™ assesses for 14 oncogenic HPV types [16, 18, 31, 33, 35, 38, 44, 50, 51, 55, 57, 58, 65, 67]. It is affordable (<US$ 5 per test). The results are available in 3 h compared to 7 h for HC2. It requires very basic laboratory supplies—for example, no running water is required—making it simpler to perform. This test was evaluated in 2,400 women in Shanxi province, China. Sensitivity was 90 % and specificity was 84 % compared to cytology at 41 and 95 %, respectively [91].

Advantages

An oncogenic HPV test is objective, reproducible, and less demanding in terms of training, and it can be performed by a technician, and quality assurance is easier to demonstrate compared to cytology [11]. Because of the excellent negative predictive value of the test, it provides 5–10 years of reassurance against high-grade disease, thus allowing for an increase screening interval [92].

One of the unique attributes of the oncogenic HPV test is that it provides an opportunity for a woman to complete the test by herself without a pelvic exam. This self-sampling of the vagina, although less sensitive (74 %) and less specific (84 %) than a physician-acquired sampling test from the cervix, is a potential option for hard-to-reach populations (i.e. due to geographic isolation or populations where there is a cultural hesitancy to pelvic examinations). Self-sampling should increase population coverage among women who are uncomfortable with provider-conducted screening (i.e. fear of speculum exam, loss of privacy, resistance from spouse) [11, 93–102]. Self-sampling is cost-effective and reduces time to do screening [103]. It is highly accepted by women [103, 104].

Limitations

An oncogenic HPV test involves doing an endocervical swab and this should not be done in pregnancy [57]. Laboratory equipment and reagents are required even for the careHPV™ test [57]. Laboratory technicians do require some basic training [57]. There is a cost for the equipment to take and perform the test [57, 105]. Currently, the algorithms for using the test are not clearly defined. This is important as the lower specificity of the HPV test means that a “see-and-treat” policy would result in a high number of women with infection, but not dysplasia, being treated. Using a second test after a positive HPV test (prior to referral to colposcopy) could involve cytology or VIA triage, which increases the number of appointments, with the associated compliance problems, and increases cost [57].

In conclusion, screening does identify precancerous lesions and results in a stage shift to earlier stages of disease and therefore benefits women. This meets prerequisite four of the WHO guidelines for screening.

Diagnosis

In high-resource countries, women with an abnormal result on a screening test often go for further diagnostic assessment. This usually involves a colposcopic assessment with cervical biopsies. The colposcope was first introduced by Hans Hinselmann from Germany in 1925. It allows for magnification (5- to 15-fold) and illuminates the cervix. The cervix is examined once the speculum is placed and then again after the application of acetic acid. Features indicative of high-grade dysplasia include a well-demarcated white lesion (Fig. 6.6) near the squamocolumnar junction, especially if there is an abnormal vessel pattern with punctuation or mosaicism (Fig. 6.7). The more severe the dysplasia, the more it is characterized by an opaque colour of the lesion, well-demarcated boarders, and a coarser vascular pattern. Visualizing the lesion with a green filter can often enhance the vascular pattern (Fig. 6.8). The adequacy of the colposcopic examination involves assessing whether the extent of the lesion can be seen, especially into the endocervical canal. Colposcopy is a subjective assessment and thus requires training and ongoing quality assurance. Many jurisdictions (i.e. British Columbia, Canada, and the UK) have an accreditation system for certifying and ongoing assessment of medical staff that perform colposcopy.

Fig. 6.6
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Colpophotograph of a white lesion

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Fig. 6.7
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Colpophotograph of mosaicism

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Fig. 6.8
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Colpophotograph with the green filter (a) and without the green filter (b)

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Efficacy

Although colposcopically directed biopsies have been the gold standard against which screening tests have been evaluated, when colposcopically directed biopsies are assessed against larger excisional biopsies or hysterectomy, the sensitivity of colposcopy is only 44–77 %, the specificity is 85–90 %, and the positive predictive value is low [106, 107]. More recently, the use of colposcopically directed biopsies was evaluated in China against routinely completing four quadrant biopsies and an endocervical sample. The latter procedure identified more disease (p  =  0.03 to p  <  0.001) [108–112].

Advantages

A colposcopic exam with biopsies means that only women with histologically proven high-grade dysplasia are offered treatment. Women with a cytology assessment that shows high-grade disease but a non-confirming biopsy are usually offered further assessment with a cone biopsy (to be discussed later in this chapter).

Limitations

A colposcopic examination requires at least two visits: one visit for assessment and one for the provision of results and counselling around next steps. Colposcopy is usually available only at specialized centres, and this increases the direct payment (for the assessment and the evaluation of the biopsies) and indirect costs (travel to attend the examination, childcare costs, lost time from work) that a woman assumes. For these reasons, women may not comply with this strategy. Colposcopy requires pattern recognition training for both colposcopists and pathologists. Colposcopy requires expensive colposcopy and pathology equipment that requires maintenance and replacement parts. Colposcopy requires a reliable electrical supply.

Treatment of Precancerous Lesions

Once high-grade disease is identified, there are several treatment options available for removing the lesion (i.e. cryotherapy, loop electrosurgical excisional procedure (LEEP), laser, cold-knife cone biopsy, and hysterectomy) for removing the lesion. Each option has its own attributes and limitations.

Cryotherapy

Cryotherapy has been in use for more than 40 years. Cryotherapy means the cells are exposed to temperatures of −20̊  C for more than one minute and so undergo cryonecrosis. Cryotherapy is mainly used to treat small lesions on the ectocervix. Cryotherapy leaves no histological sample for assessment. The procedure involves visualizing the cervix, the cryotherapy probe with its circular metal tip is applied to the ectocervix, and a refrigerant gas (either nitrous oxide or carbon dioxide) is allowed to flow through the instrument cooling the metal tip. With cervical tissue, the recommendation is to freeze for 3 min, allow a thaw for 5 min, and then refreeze for three minutes [113, 114].

Efficacy

With cryotherapy, 90 % of women with dysplasia are disease free at one year after treatment. Efficacy decreases as the severity of the disease increases; for example 83–100 % of CIN 1 cases are disease free at one year compared to 65–95 % of CIN 2 cases and 55–92 % of CIN 3 [115]. Eighty-five percent of women found the procedure acceptable [60].

Side Effects

Immediate side effects from cryotherapy include mild to moderate cramping and/or fainting during the procedure [60, 114]. During the first couple of weeks after the treatment, there is a profuse, watery, vaginal discharge [60, 114]. Cervicitis and/or PID can occur in 1 % of women [53, 57, 114], vaginal wall injury in 0.1–0.8 % [114], and hospitalization in 0.5–1 % [114]. Long-term complications can include cervical stenosis or infertility, but these are rare [114]. Following cryotherapy, it is difficult to assess the squamocolumnar junction in future colposcopic evaluations.

Advantages

Cryotherapy requires no anaesthesia or electricity. The equipment is portable, and the consumables are low in cost. With adequate training and supervision, primary health-care professionals (i.e. nurses) can provide cryotherapy [116].

Limitations

Cryotherapy is not recommended in the following situations: pregnancy; women who have large lesions involving more than three quadrants; a lesion which extends beyond the cryoprobe by 2 mm; endocervical lesions; a lesion that extends onto the vagina; situations where there are polyps, ulcers, a distorted or atrophic cervix; situations where cervicitis or PID is present; a bleeding diathesis; vaginal wall prolapsed causing inadequate visualization of the cervix; or any lesion suspicious for cancer. If a lesion has not resolved after two cryotherapy sessions, the patient should have a cone biopsy. The equipment must be properly decontaminated before reuse to prevent spread of infection (usually in 10 % bleach solution or 70 % ethyl alcohol). The costs of cryotherapy involve the cryotherapy unit ($400/unit), the carbon dioxide or nitrous oxygen gas, the tank, and the refrigerant. There has been an issue with clogging or blockage of the gas flow within the cryo unit, and various techniques exist to deal with these problems [117].

Loop Electrosurgical Excisional Procedure or Large Loop Excision of Transformation Zone

LEEP involves the use of a fine wire to excise a lesion from the cervix. The loops come in various sizes and shapes. The loops attach to a handheld apparatus that allows for cutting or coagulation settings. The handheld piece is attached to an electrosurgical power generator. A smoke evacuator is used to minimize the plume. When doing a LEEP, a specially coated speculum should be used. The cervix is usually washed with Lugol’s iodine to ensure that the physician sees the extent of the lesion. Some physicians would use local anaesthetic to minimize the woman’s discomfort during the procedure. Some physicians add epinephrine or vasopressin to minimize bleeding.

Efficacy

LEEP, laser, and cold-knife cone all have the same efficacy (reduction of invasive cancer by 95 % for at least 8 years) [106, 118–120].

Side Effects

Immediate side effects from a LEEP include cramping or pain. This pain is no different in severity or duration compared to cryotherapy [114]. During the first days after a treatment, all patients have some vaginal discharge [114] or bleeding. Significant bleeding can occur in 2 % of women and is usually related to the extent of the procedure and/or a superimposed infection [114]. Vaginal wall injuries occur in 0.4–4.4 % of women. Cervical stenosis is a long-term complication that occurs in 4–6 % of women [114]. Of all of the treatment options, LEEP is the maneuver that most likely allows preservation of the squamocolumnar junction for future assessments. Long-term complications can include premature rupture of membranes (OR 2.69, 95 % CI 1.62–4.46) [120, 121], preterm delivery (OR 1.81, 95 % 1.18–2.76), low-birth weight infants (<2,500 g) (OR 1.60, 95 % CI 1.01–2.52), and cervical stenosis [120, 122].

Advantages

LEEP can be used for small or large lesions of the cervix [123]. LEEP provides a histological specimen for confirmation of the extent and severity of disease. The LEEP specimen may involve one pass or multiple passes. Adequacy of excision is more difficult to assess when there have been multiple passes. Access to the coagulation setting on the handheld device allows an immediate resource to stop bleeding in the event that this is an issue.

Limitations

Compared to cryotherapy, LEEP requires more training and is usually only performed by physicians in specialized centres; these requirements have implications for patient access to care. It requires more equipment (i.e. electrocautery generator, one-time use loops, handheld disposable devise, smoke evacuator with tubing and filters, specialized speculums to minimize transduction of heat) and so the cost is higher. It requires a reliable electrical supply. Although LEEP provides a histological specimen, the cautery artefact at the edges of the sample may make it difficult to assess the adequacy of excision (i.e. margins) in some cases.

Laser

Laser involves using a very high energy light beam to either evaporate the cells of the high-grade lesions or excise them. The laser works by being attached to a colposcope. A smoke evacuator is necessary. Everyone in the room must wear eye protection and masks to filter evaporated particles/plume. Any flammable material (sheets, paper drapes) must either be moved away from the area of work or made wet to decrease the risk of fire.

Efficacy

As listed for LEEP.

Advantages

The advantages are the same as those listed for LEEP. The laser energy beam can be defocused to deal with immediate bleeding. The laser is very useful for dealing with lesions that extend onto the vagina/vulva.

Limitations

Laser requires very expensive equipment (i.e. laser power source, micromanipulator, colposcope, galvanized speculum, smoke evacuator with tubing and filter, eye protection for everyone in the room, CO2 gas). It requires a reliable power supply. The laser requires access to replace parts. There is a need for both extensive training and experience for the physician operator, the nurse staffing the laser control panel, and a biomedical engineer for dealing with equipment issues. Although laser excision provides a histological specimen, due to cautery artefact, it may be difficult to assess the margins.

Cold-Knife Cone

A cold-knife cone is usually recommended for those lesions where (1) the endocervical extent of the disease is not visible; (2) the work-up suggests adenocarcinoma in situ or possible malignancy; or (3) there is a significant discrepancy between the cytology result with a negative colposcopically directed biopsy.

A cold-knife cone biopsy is performed in the operating room with the woman either under general anaesthesia or under epidural or spinal block. The physician washes the cervix with Lugol’s iodine solution to outline the extent of the lesion. The cervix is infiltrated with Xylocaine® with epinephrine/vasopressin. Stay sutures are placed at 3 and 9 o’clock. A knife (i.e. “beaver blade”) is used to remove the lesion, and the ultimate defect is in the shape of an inverted cone. Pathology can assess the severity of the lesion and if the lesion has been completely excised or if any of the margins (deep endocervical, lateral, or ectocervical) are involved. A post-cone endocervical curettage (ECC) helps define if disease is still present above the level of the excised specimen. Any bleeding from the defect in the cervix can be cauterized, sutured, covered in thickened ferrous sulphate, or packed with an agent like Surgicel R or Fibrillar TM (Ethicon, Somerville, NJ).

Side Effects

The immediate risks of a cold-knife cone biopsy are related to the anaesthesia risk from spinal, epidural, or general anaesthetic and bleeding. There is a 9 % post-cone bleeding risk, which usually occurs 7–10 days post-procedure and is usually related to a superimposed infection. Long-term sequelae include PTROM, preterm delivery (RR 2.19, 95 % CI 1.93–2.49), low-birth weight (2.53, 1.19–5.36), caesarean section (3.17, 1.07–9.40), and cervical stenosis [22, 124]. The future ability to assess the squamocolumnar junction is compromised by a cone biopsy.

Advantages

Cold-knife cone biopsy provides a histological specimen where margins can be easily assessed.

Limitations

Cold-knife cone biopsy requires access to an operating room, an anaesthetist, and surgeon. The cost is very high.

Hysterectomy

A hysterectomy may be recommended when screening and diagnostic tests show that disease persists after attempted conservative treatment.

Hysterectomy is the definitive way to remove cervical disease, especially in a woman who has completed her childbearing. A hysterectomy involves removing the cervix and uterus with or without the tube and ovaries. A hysterectomy can be completed by the vaginal route, by the abdominal route with a Pfannenstiel or vertical incision, or by laparoscopic approach.

Side Effects

The immediate risks are bleeding, infection, thromboembolic disease, and injury to surrounding structures (i.e. bladder, bowel, or ureters). Hysterectomy has the highest rate of complications. Recovery from surgery takes 4–6 weeks.

Advantages

Hysterectomy provides the best histological specimen for evaluation. It is definitive treatment for the cervical disease.

Limitations

Hysterectomy can only be performed in specialized centres. It is the most costly treatment strategy. It results in loss of fertility.

Assessment of Treatment Options

All five treatment options demonstrate that effective treatment is available for pre-invasive or early invasive disease, meeting the third WHO (i.e. prerequisite of effective treatment being available) [1]. Clearly, the first four treatment options for managing presymptomatic disease allow preservation of fertility with minimal side effects meeting the fourth WHO prerequisite (i.e. treatment of presymptomatic disease results in benefits beyond those obtained through treatment of symptomatic disease) [1].

Approaches to Screening, Diagnosis, and Treatment for Cervical Disease

There are several approaches to screening, diagnosis, and treatment of cervical disease. Three approaches are described here. The “traditional approach” is to screen using cervical cytology, diagnose disease using the colposcope, confirm disease with a biopsy, and then treat the disease using LEEP. An “intermediate approach” is to screen using an oncogenic HPV test, diagnose using either VIA or cervical cytology, and then treat with cryotherapy. The “screen-and-treat” approach is to screen with VIA and treat using cryotherapy at the same visit.

The “traditional approach” that has evolved in high-resource settings includes cervical cytology, colposcopic examination for those with an abnormal screen, biopsy confirmation, and LEEP. It involves multiple visits: a visit for the Pap test, a visit to get the results, a visit to another consultant for the colposcopy exam and biopsies, another visit for the results, a visit for the LEEP procedure, and one or more follow-up visits to ensure that the disease has been removed. To minimize loss to follow-up, various programmes have developed “call recall” systems to remind especially non-compliant women. This traditional approach is costly to the health-care system and to the woman (i.e. travel, childcare, lost time at work). This multiple visit approach has not been successful in low-resource settings for two reasons: low compliance and lack of access to treatment at the point of care. Thus, in low-resource settings, this strategy has resulted in poor outcomes.

The “screen-and-treat” approach, otherwise known as the “same visit treatment” or “see-and-treat” approach, is a single visit for screening and treatment. This approach minimizes the chance that an abnormal finding goes unmanaged. To be successful the screening test must provide results rapidly and accurately. The treatment must also be safe, appropriate to the training of the staff, and effective. For screen and treat to be successful, both components need to happen at the same visit. The infrastructure must be simple without the need for specialized care. The screening test could be a rapidly read cervical cytology, careHPV™ test, or VIA. Although attempted with cervical cytology, the problem is the time to complete the cytological assessment [51, 125]. The treatment can be cryotherapy or LEEP [59]; however, cryotherapy has many advantages in the low-resource setting.

Efficacy

As described previously, a “see-and-treat” approach was used in 80,000 women in India aged 30–59 years. There was a 25 % reduction in cervical cancer incidence and a 35 % reduction in cervical cancer deaths compared to a non-screened group [51, 73, 126].

A safety study of the “see-and-treat” approach in Thailand using VIA as the screening test and cryotherapy as the treatment showed that, among women who were VIA positive and were treated, 94.3 % were disease free at one year (i.e. VIA negative). These results have been replicated in other settings like Ghana [42]. However, such excellent results are not universal. For example, in Osmanabad, India, the success rate was only 50 % [21], and in Dindigul, in Southern India, there was no benefit [127].

A different “see-and-treat” approach was used in South Africa. Here 6,555 nonpregnant women aged 35–65 years received either HPV test (HC2), VIA, or no screening test. They were randomized to immediate or delayed treatment with cryotherapy. Treatment was given if the woman was HPV positive or if they were VIA positive. The rates of dysplasia were lower in both groups at 6 and 12 months. Safety and feasibility were confirmed [76]. In the subgroup of women followed to 36 months, those with a positive HPV test (HC2) and treatment had the greatest benefit [76].

A cost-effectiveness study assessed several screening strategies involving India, Kenya, Peru, South Africa, and Thailand. Screening women once in their lifetime at age 35 years with a one or two visit screening strategy involving VIA and cryotherapy at the same visit was the most cost-effective strategy [94, 128]. This strategy reduced lifetime risk of cancer by 25–36 % and cost less than $500 (international dollars) per year of life saved [93]. This strategy had a cost-effectiveness ratio less than the country’s per capita GDP. According to the Commission on Macroeconomics and Health, this is considered very cost-effective [129]. To put this in the context of other well-known public health interventions, this strategy was as cost-effective as Hepatitis B vaccination in India, second treatment for TB in Peru, and malaria prevention with nets in Kenya.

Limitations

The limitations of this approach are the limitations listed for each of the components. In addition, some national decision makers will not accept the “see-and-treat” approach if cervical cytology and colposcopy are currently available within the country [130].

Cervical Cancer Prevention Programme

There are several of ways to implement a cervical screening programme. Opportunistic cervical screening means that the woman initiates the interaction to be screened, or a woman who sees a physician for another reason is offered the opportunity to be screened at that visit. In contrast, an organized screening programme involves a clear system of education, age-appropriate invitation to screening, access to screen and treatment, quality assurance, and programme evaluation.

According to the International Agency for Research on Cancer (IARC), there are eight essential features an organized screening programme:

  1. 1.

    A clearly defined target population

  2. 2.

    Eligible screening participants are identifiable (e.g. a list with names and addresses)

  3. 3.

    Processes are in place to maximize reach and encourage participation (e.g. personalized invitation letters)

  4. 4.

    Suitable field and lab facilities exist for collecting and analysing specimens

  5. 5.

    Systematic quality-control procedures are in place to assess how tests are performed and interpreted

  6. 6.

    Appropriate facilities exist for diagnosis, treatment, and follow-up of patients with confirmed abnormalities

  7. 7.

    An organized referral system is in place to manage any identified abnormalities and provide information about normal results

  8. 8.

    An organized performance measurement/monitoring system is in place to enable collection of relevant and timely epidemiological data [131]

Studies from the Nordic countries and the Netherlands have shown that when such programmes are in place there is a significant drop in cervical cancer incidence and mortality [132–135]. Next, we present examples from low-resource setting that highlight problems and successes in cervical cancer prevention.

Problems

Organization

It is important that an organized programme encompasses training of health-care providers involved in screening (family doctors, nurses, colposcopists, cytologist, cytotechnician). The literature focuses especially on training in cytology [136]. An example of why this is so important is that, in some countries such as Argentina, up until recently gynaecologists read the Pap test [137].

The programme needs to ensure equipment and supply chain, and high-quality lab services. Honduras is an example where 80 % of the population is screened, but there is an extremely high false-negative rate of Pap smears. In part, this is due to poor Pap smear quality as a result of lack of supplies such as fixatives, spatulas, and cytobrushes [90, 138].

An organized programme also needs to establish a referral pathway for assessment and treatment of women with abnormal results. Capacity needs to be developed to ensure treatment for pre-invasive (i.e. colposcopy, LEEP) and invasive disease (radical surgery and radiation therapy). In Central and South America, coverage is high but a woman’s access to treatment is poor; thus, rates of cervical cancer remain high [49, 139, 140].

The population needs to be educated concerning cervical cancer and prevention opportunities. Studies show that participation in screening programmes is proportional to awareness and knowledge [141–143]. There are numerous studies from low-resource settings showing that women are unfamiliar with cervical cancer and HPV infection as the cause of cancer [142, 144–147].

Screening tests and the way they are implemented also need to be culturally relevant to ensure patient participation [148–150].

Extent of Use

It is clear that screening benefits older women (30 and above) and that overscreening harms women in their teens. Thus, the emphasis of screening should address participation rates in a target population. A review of cancer screening in 57 countries using data from 2002 found that only 18 % of 25- to 64-year-old women in developing countries had a pelvic exam and Pap test in the last 3 years [151]. Screening occurs at even lower rates of <1 % in Bangladesh, Ethiopia, and Myanmar; <10 % in Ethiopia, Bangladesh, and Malawi.

Data Registration

A centralized database for detailed information on the date and result of a screen and follow-up tests for abnormal results allows tracking for compliance with follow-up. When a review was conducted in Peru, it was identified that 56 % of women with high-grade Pap tests were lost to follow-up and 3 % died of cervical cancer [152].

Successes

Organization

Prior to undertaking a cervical screening programme, each country needs to define whether cervical cancer is a problem in their jurisdiction by assessing incidence and mortality from the disease. Next, they need to determine whether there is the political will to designate resources toward developing an effective plan, implementation, and monitoring [153]. A cervical cancer prevention programme involves more than just the screening test. A cervical screening programme encompasses all of the services, from provision of the test to diagnosis and treatment [81]. An organized programme involves national policies that define, among other things, the ages during which screening is to occur, the screening interval, and the method of screening. These guidelines are to be implemented on a population basis with effective recruitment strategies to achieve high coverage. This could involve access to a population-based cancer registry and a computerized call and recall system.

In Vietnam several agencies came together to launch a population-based Pap smear screening system in Ho Chi Minh City (150 women per day). They developed community outreach methods, quality control, and quality assurance programmes with a centralized cytology lab and access to curative treatment [129].

In Chile, prior to 1987, only 10 % of women were screened annually. In 1987, the Chilean Ministry of Health and WHO collaborated to train health professionals, establish a system of patient follow-up, improve cytology accuracy, and improve patient education. In 1990, screening coverage increased to 66 % for women aged 25–64 years. Mortality from cervical cancer fell by 39 % by 2001. This is a success story showing that reallocating resources and infrastructure led to a fall in cervical cancer rates [49, 90, 154].

Another aspect of organization involves incorporating screening into the existing health-care system. The system of HIV care in Africa has taught us that cervical cancer screening is feasible and acceptable within the setting of an HIV care and treatment clinic. An example of this is in Nyanza province on the shores of Lake Victoria in Kenya. Collaboration was built between the Family AIDS Care and Education Services Program (FACES) and the University of California, University of San Francisco, and Kenya Medical Research Institute, Nairobi, Kenya, to provide cervical cancer screening for HIV-positive women [155, 156].

A similar successful collaboration has been described in Zambia between the University Teaching Hospital in Lusaka and the University of Alabama at Birmingham, and the Center for Infectious Disease Research in Zambia and the Zambian Ministry of Health [105, 123, 157, 158].

A programme should encompass training of health-care providers like cytologists. The Argentine Society of Cytology [137] mandated certification of professionals by scientific organizations according to national and international standards to ensure professional standards. Certification of professionals was felt to be a prerequisite to lab certification.

A programme needs to identify mechanisms to ensure attendance for screening or follow-up. Transportation incentives increase adherence to follow-up [159, 160].

HIV care has taught health planners in Africa that if you want people to adhere to treatment you have to work with community health workers. They live in the villages with their neighbours. They are a source of education and reinforcement [161]. Personalized follow-up letters increase adherence to follow-up [159, 160]. Counselling and telephone calls increase adherence to treatment appointments and follow-up [159, 162].

Method of Quality Assurance

The Argentine Society of Cytology [137] currently mandates that first screen must be carried out by cytotechnicians under supervision of a pathologist who re-reads 100 % of abnormal smears and a percent of normals. Labs should read 10,000 smears annually [137].

Peru uses lab certification by the Peruvian Scientific Society of Cytology after they verify certain conditions, including that a certain number of Pap smears are read annually [137].

The United States implemented the Clinical Laboratory Improvement Amendment, which involves an evaluation of eight steps within the lab system as a means of evaluating and maintaining cytology quality [163].

Monitoring Systems are built for the purpose of evaluation through performance indicators and quality assurance (i.e. cytology assessment). Performance indicators can include documenting the coverage, interval from the test to reporting the results, proportion of unsatisfactory Pap tests, treatment compliance, timeliness of follow-up of abnormal results, sensitivity, specificity, and interval cancers. Use of these indicators has pointed to areas where improvement is needed.

When follow-up was assessed in three rural areas of Honduras that offered cytology screening, it was identified that when VIA was followed by immediate colposcopy, compliance was 83 %. When Pap test was followed up by an appointment to give results and then colposcopy, compliance was only 38 % [164].

The programme needs to have a designated management team responsible for planning, implementation, and evaluation [163, 165].

Conclusion

In this chapter, we identified four prerequisites necessary for defining whether a mass screening programme should be developed. We have shown that cervical cancer is one of the leading cancers in women, especially in low-resource settings, and it is a major cause of mortality. Cervical cancer is preceded by a long asymptomatic phase of disease. Several screening strategies can be used to identify precancer, and, if treated, the screening programme can decrease the occurrence of cancer or shift the presentation of cancer to earlier stage, which, when treated, results in low mortality. Organized screening programmes provide the best population prevention of disease with the lowest rate of harm. Various models of screening, diagnosis, and treatment exist and have been assessed within the low-, medium-, and high-resource settings. Given that the four WHO prerequisites have been met, each jurisdiction must decide on the model that meets the needs of that population. For low-resource settings with limited health infrastructure, a national “see-and-treat” programme with a once or twice in a lifetime assessment with VIA or HPV testing and cryotherapy for those with positive tests will lead to a quick reduction in cervical cancer rates at low cost with low technology. The emphasis should be on screening women aged 30–49. It is important that a screening programme address the populations’ knowledge and awareness of cervical cancer and HPV, facilitate compliance with screening, followup on abnormal test result, and ensure quality control.