Screening

To date, cervical cancer prevention efforts worldwide have focused on screening at-risk women using Pap smears and treating precancerous lesions. Pap smears involve scraping
cells from the cervix, fixing and staining them on a glass slide, and having them evaluated by a trained cytologist. Where screening quality and coverage have been high, these efforts have reduced invasive cervical cancer incidence by as much as 80 percent.12 

Effective Pap screening faces challenges. 

• Although Pap smear-based screening efforts have been introduced in several developing countries, many have achieved only limited success. Problems have included:
• screening is offered opportunistically (often for a fee) to younger, relatively low-risk women;
• cytology services are limited and/or of poor quality;
• follow-up diagnostic and treatment services are unavailable to most women; and
• clients often do not understand that having a Pap smear is important to cancer prevention.13

In most countries, developing systems to ensure access to high-quality cytology services is a challenge. In Mexico, for example, the low quality of cytology services has been a major barrier. A study of 13 cytology centers found a range of problems from poor-quality services to inadequately trained technicians; the false-negative rate for Pap smears in these centers was as high as 54 percent.14 In Colombia’s cervical cancer prevention program, a shortage
of cytotechnicians has been a key barrier to achieving screening goals.2 

Efforts to improve the quality of the Pap smear itself are ongoing. For example, the ThinPrep® slide system uses a liquid-based cytology system to produce slides that, in general, are easier to read with fewer difficult-to-interpret slides. The slides can be read either by a cytologist or an automated Pap smear reading machine. This approach adds considerable cost to Pap smear-based programs, however, and requires technical capability that is difficult to maintain in many settings.

Several alternative approaches to screening women at risk of cervical cancer currently are being investigated. These include visual screening to identify cervical lesions and HPV tests to identify women at high risk for dysplasia. 

Visual inspection: an alternative to Pap smears.

Given the difficulty of ensuring high-quality cytology-based services in many settings, there is significant interest in new approaches to screening for precancerous lesions. Of these, visual inspection of the cervix is a promising option, especially for low-resource settings. Early studies of visual inspection involved simply looking at the cervix for any signs of early cancer. Also known as “downstaging,” this approach was not effective generally should focus on high-grade dysplasia, in identifying precancerous conditions.15 By contrast, visual inspection after swabbing the cervix with an acetic acid (vinegar) solution highlights differences in cell structure and absorption rates, and causes precancerous cells to turn white. One study found that when combined with Pap smear screening, visually inspecting the cervix after a one-minute acetic acid wash improved detection of cervical disease by 30 percent.5

Visual inspection with acetic acid (VIA). 

VIA is defined as visual inspection of the acetic acid-swabbed cervix without any magnification. The cervix is illumi-nated with a light source and examined with the naked eye by a trained health care worker. Although protocols have varied, results of several studies in developing countries suggest that VIA is as sensitive as Pap smears in detecting high-grade dysplasia in many settings, although not as specific.

A 1996 study of 2,426 women in South Africa found that VIA detected more than 65 percent of high-grade lesions and invasive cancer and, according to the study authors, warranted consideration as an alternative to cytologic screening.16 A 1999 study in Zimbabwe used nurse-midwives to perform the screening exam. The study reported that the sensitivity (proportion of true positives identified as positives) and specificity (proportion of true negatives identified as negatives) of VIA in detecting HSIL were 77 and 64 percent, respectively, compared to 43 percent and 91 percent for Pap smears.17 A study of 1,351 women in India found that VIA performed by trained nurses detected 96 percent of moderate-severe dysplasia and cancer, while Pap smears (obtained by trained nurses and examined by a cyto-pathologist) detected 62 percent. The specificity of VIA for detecting these lesions was 68 percent.18 

Some studies of VIA have added low-power magnification to the procedure. This approach—called VIA with magnification (VIAM)—currently uses a low-power (4x), hand-held visual inspection device with a built-in light source (an Aviscope ™ ) to examine the cervix after application of acetic acid. A small Indonesian evaluation of an earlier version of the device indicated that VIAM may be acceptably sensitive and specific (over 90 percent) in identifying moderate to severe cervical lesions. It is not yet known if use of the Aviscope offers a significant advantage over VIA without magnification, although the potential for increased specificity is of particular interest. Several studies in developing countries are underway to assess its ability to provide accurate results. 

Many aspects of VIA make it an attractive approach for use in low-resource settings. VIA is a relatively simple, low-tech approach that is minimally reliant upon infrastructure for performance. Non-physicians can perform the procedure, provided that they receive adequate and ongoing training. Furthermore, results of the procedure are available immediately, making it possible, in principle, to provide treatment during the same visit (see page 5). However, VIA is less effective for screening postmenopausal women because physiological changes make observation of cervical lesions difficult. This limitation should be taken into consideration by all
screening programs using VIA. Pap smears also can be more difficult to obtain in postmenopausal women. 

As countries begin to evaluate broad-scale use of VIA, it is important to consider the issue of false-positives and determine the balance between false-positives and false-negatives that is consistent with local health policy and programmatic capabilities. Regular training of health care providers is an important component of any cervical cancer prevention program. Because VIA is an entirely provider-dependent screening method, clear standards for identifying the precancerous lesions that should be treated are essential, along with approaches for ensuring that providers make appropriate judgments, both after initial training and throughout routine service provision. Other visual inspection approaches also are being used. For example, Cervicography® involves taking photographs of the cervix through a specially equipped camera. Once developed, the photographs (called cervigrams) are projected as slides and interpreted by specially trained colposcopists. While the sensitivity of Cervicography can be comparable to cytology, as with other visual inspection approaches, specificity appears to be lower.19 Cervicography is relatively expensive and requires a reliable logistics infrastructure. 

HPV testing. 

There is growing interest in the potential for using HPV testing in cervical cancer prevention programs. While epidemiological and technical barriers remain, several scenarios have been suggested. The most commonly proposed approaches are to use positive HPV tests to (1) identify women with low-grade dysplasia who should be managed more aggressively; (2) determine which women treated for high-grade dysplasia should be monitored more closely; and (3) determine which women aged 35 and older are at greatest risk of high-grade dysplasia.

Recent data point to the potential for using HPV testing as a primary screening strategy in older women. For example, one study evaluated the use of the Digene Corporation’s Hybrid Capture® II (HC II) test (which detects the presence of 18 high-risk HPV types in cervical/vaginal specimens) to identify women likely to have high-grade lesions and cancer. The study involved more than 9,000 sexually active women aged 18 and older in Guanacaste Province, Costa Rica, and found that HPV testing detected 88.4 percent of high-grade lesions and cancers. The HPV test demonstrated greater sensitivity than Pap smears in this setting (88 versus 78 percent) but lower specificity (89 versus 94 percent). When results were calculated by age group, specificity was highest (94 percent) in women aged 41 and older.20

A second study evaluated the HC II test’s ability to identify women likely to have high-grade lesions and cancer among more than 1,400 previously unscreened black South African women aged 35 to 65. HPV testing (using self-collected vaginal samples) was more sensitive than Pap smears (66 versus 61 percent) in this population, but less specific (as the false-positive rate was 17.1 percent for HPV testing, and 12.3 percent for Pap smears). These differences, however, were not statistically significant.21

Key barriers to further exploration of HPV test protocols in low-resource settings are cost and technical requirements. In the U.S., the current HC II test retails for about US$22 per test, takes six to seven hours to process, and requires access to laboratory equipment and a computer. A simpler, less-expensive, but equally accurate test will be required before screening protocols utilizing HPV testing can be initiated in most developing countries.