PATH's Cervical Cancer Prevention Action Planner

Screening and treatment of precancerous lesions

Screening

Cervical cancer screening of sexually active or formerly sexually active women can determine whether they are at risk of developing cervical cancer. This determination can be made by examining the cells gently scraped from the cervix using the Pap test; by examining the surface layer of the cervix through visual inspection; or by detecting HPV DNA from cervical swabs.39,47 The Alliance for Cervical Cancer Prevention promotes ten findings and recommendations for effective cervical cancer screening programs.

Cytologic screening (Pap)

Since its introduction more than 50 years ago, the Pap or cervical smear has been used throughout the world to identify precancerous lesions for treatment or follow-up. Routine use of Pap smear screening in the industrialized world has contributed to the 70% to 80% reduction of cervical cancer incidence in developed countries since the 1960s.48 Even in industrialized countries, however, the level of success can vary. For example, in the United States, where an overall decline in the number of cervical cancer cases has occurred, rates nonetheless remain high in impoverished areas.49

Pap smear

Lack of similar success in developing countries can be attributed to limited resources (i.e., supplies, trained personnel, equipment, quality control, health care infrastructure, and effective follow-up procedures).48 As noted earlier, screening programs in developing countries either do not exist or have not proven to be sustainable or effective.1 One estimate is that about 75% of women in industrialized countries have been screened within the preceding five years. In contrast, a survey in India found that only 2.6% of women had been screened.50 Estimates in Kenya suggest that only 1% of participants had ever undergone any screening, despite numerous efforts to improve screening programs. One factor compounding the problem is that both women and health care workers often lack information about cervical disease and how to prevent it.51,52

Limitations of cytology

A single cytologic screening results in a high rate of false-negatives—that is, it lacks sensitivity and cannot detect many cervical abnormalities, making repeat screening necessary. Pap smear failure can be a consequence of the health care provider’s sampling technique or ability to read the smears. In addition, the need for follow-up medical appointments to present the results and manage any abnormalities can negatively affect treatment rates when women are unable to return for treatment appointments.15,39

Efforts to improve the reliability of Pap smears in the last ten years include the development of liquid-based cytology, which uses a small amount of fluid to preserve cells collected from the cervix, rather than directly smearing the cell sample onto a glass microscope slide. This method has greater laboratory efficiency, but in some countries, it adds to the cost of the test, has not been shown to have better accuracy, and requires additional instruments. For these reasons, it may not be well-suited for use in many low-resource settings.48,53 In addition, computer technology is now being used to identify the most abnormal areas on a Pap smear slide, thereby reducing the subjectivity of assessments and increasing the test’s sensitivity—however, this technology is also quite expensive.

Alternatives to cytology

Several new types of screening methods are either available now or under development. Ideally, the most effective screening method would be accurate, inexpensive, painless, and simple to perform; socially and culturally acceptable; without adverse effects; and able to provide immediate results. Some promising new methods may bring cervical cancer screening closer to this ideal.48,51,53

Visual inspection with acetic acid

Visual inspection with acetic acid (VIA) can be an alternative to cytologic testing or can be used along with Pap or HPV DNA screening. VIA involves washing the cervix with 3% to 5% acetic acid (vinegar) for one minute and observing the cervix with the naked eye afterward. If characteristic, well-defined white areas are seen near the transformation zone, the test is considered positive for precancerous cell changes or early invasive cancer. VIA does not require a laboratory or intensive staff training. The results are immediately available, allowing treatment at a single visit and thus reducing loss to patient follow-up. VIA’s sensitivity is as good as or better than that of the Pap smear, but like the Pap smear, visual inspection is subjective, and supervision is needed for quality control of visual inspection methods. VIA does not work as well in postmenopausal women because the transformation zone recedes into the cervical canal at menopause and cannot be seen with VIA.51,54

An additional advantage of VIA not offered by Pap or HPV DNA tests is that it allows providers to identify the small proportion of positive lesions that are unsuitable for treatment with cryotherapy, a mode of treatment appropriate for limited-resource settings (see Treatment of precancerous lesions below). An implication of this is that whether primary screening is done by Pap, VIA, or HPV testing, the decision not to treat with cryotherapy can be made only with VIA (unless a colposcope is available). VIA therefore can be used as a primary screening test or for treatment triage subsequent to primary Pap or HPV testing.

Visual inspection with Lugol’s iodine (VILI) is similar to VIA. However, data on VILI’s sensitivity and specificity remain limited.

HPV DNA testing

New tests can detect DNA from cancer-causing HPV types in vaginal or cervical smears. A sample of cells is collected from the cervix or vagina using a small brush or swab, and the specimen is sent to a laboratory for processing. One advantage of HPV DNA testing is that when conditions are ideal, it is not as subjective as visual and cytologic screening. A review of studies concluded that HPV DNA testing is particularly valuable in detecting high-grade precancerous lesions in women older than 30. HPV infections in women younger than 30 are likely to clear up by themselves, so testing women at that age would lead to frequent overtreatment.55,56

The Cervista™ HPV tests

The United States Food and Drug Administration has approved an HPV DNA test called Cervista HPV 16/18 (Hologic™, Inc.), which detects DNA for HPV types 16 and 18. Another test, the Cervista HPV HR (High Risk) test, which detects most oncologic HPV types, also has been approved.57

The Hybrid Capture® 2 test

The US FDA has approved the HPV DNA detection assay Hybrid Capture 2, which was developed by QIAGEN, Inc. (formerly Digene). This test can detect 13 high-risk types of HPV and 5 low-risk types. It is more sensitive than visual inspection methods and cytology, but it is unaffordable for low-resource areas. In addition, the test requires laboratory facilities, special equipment, and trained personnel.58,59

The careHPV™ test

A new test called careHPV™ (QIAGEN, Inc.), based on Hybrid Capture 2 technology, has been developed specifically for use in low-resource settings. This test is able to detect DNA from 14 cancer-causing types of HPV, with test results available in two to four hours. CareHPV should become available commercially sometime in 2010 or 2011, and if it proves to be simple, rapid, accurate, and affordable, it may be a suitable screening tool for low-resource settings.59 One issue regarding both the careHPV test and the Hybrid Capture 2 test is that they are designed to test many samples at the same time, which might affect how programs will use them.

In addition to these tests, other molecular HPV tests are under development and are likely to be evaluated soon for clinical use.

Treatment of precancerous lesions of the cervix

Women with precancerous lesions who receive treatment have a high survival rate. The affected area of the cervix may be frozen with a cold probe (cryotherapy) or removed using a heated wire loop as a knife (loop electrosurgical excision procedure or LEEP). These are both outpatient procedures that can be used in developing countries, but LEEP is quite expensive and requires more training than cryotherapy (see descriptions in Table 2). If cryotherapy is restricted to lesions that are small (i.e., about 20 mm or less), and the entire lesion is visible (does not extend into the cervical canal), treatment efficacy is 85% to 95%. Both cryotherapy and LEEP are less radical than the previous standard treatment, cold-knife cone biopsy. Although no longer the standard, cone biopsy is still used for precancerous lesions that cannot be otherwise treated, or when cancer (squamous carcinoma or adenocarcinoma) is suspected.20,60,61

Table 2 Click for reference list.

Screen-and-treat programs

In developing countries, a promising method called screen-and-treat is being used. Women who test positive on VIA or HPV DNA tests do not undergo further diagnostic testing; instead, they are treated immediately or shortly after screening with cryotherapy or LEEP.20 The screen-and-treat approach is especially appealing where transportation, time, and other access issues make follow-up visits difficult. The main benefit is that women are less likely to be lost to treatment because they cannot return to the clinic.47 Screen-and-treat programs have been evaluated in Ghana, South Africa, and Thailand with good results. The data show that VIA and cryotherapy done in one or two clinical visits, without an intermediary colposcopic and biopsy diagnostic step, is one of the most cost-effective alternatives to conventional multi-visit strategies.62-64

New paradigms for screening in the age of HPV vaccination

The success of VIA, HPV DNA testing, and cryotherapy in field settings signals new potential for cervical cancer control in places where cytology programs are not feasible or sustainable. Single-visit approaches using VIA to screen can be offered now, and screen-and-treat approaches using HPV DNA tests for primary screening and VIA for triage may be possible in the near future in many low- to medium-resource settings.

Once HPV vaccination becomes routine, and more sensitive tests than Pap or VIA are in widespread use, it is likely that the screening strategies common today (such as Pap smears repeated every one to three years, as in the United States, or every three to five years, as in other countries) will change. One proposed scenario is to vaccinate prior to sexual debut, then screen only a few times when the woman is in her 30s and 40s using HPV DNA testing (or other future molecular tests that may give a better indication of which women are at highest risk of pre-cancer).65 Such a strategy would be feasible in low-resource settings and would save considerable costs in wealthier countries.

Another concern for the future is what will happen when the current generation of newly vaccinated girls reaches the appropriate age for screening. The vaccines protect against the two HPV types that cause 70% of cervical cancer, but not against those that cause the other 30%. Some epidemiologists have raised concerns that the vaccines will diminish the quality of Pap-based screening programs. According to this thinking, as cervical lesions become less prevalent, technicians will lose their skills of interpreting specimens, so the accuracy of Pap screening will fall. In this sense, the clear and objective results of the new HPV DNA or other molecular tests will provide an advantage. More generally, the principles of public health screening will help to determine how resources should be allocated in future decades, taking into consideration factors such as vaccine coverage and cervical cancer prevalence.
Photo: PATH/Mike Wang
Woman in lab coat 


Key resources

Watch video Screening for and Treatment of Precancerous Lesions video and transcript

Screening and treatment (RHO Cervical Cancer website)

Global Guidance for Cervical Cancer Prevention and Control (International Federation of Gynecology and Obstetrics, PDF)

Comprehensive Cervical Cancer Control: A guide to essential practice (World Health Organization)

Planning and Implementing Cervical Cancer Prevention and Control Programs: A Manual for Managers (PATH/Alliance for Cervical Cancer Prevention)

Alliance for Cervical Cancer Prevention website

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