Invasive cancer of the cervix is a major cause of death from gynaecological cancer worldwide, with almost half a million cases diagnosed each year. Reported incidence rates in developing countries are much higher than those in developed countries. The reported age-standardised incidence rates per 100,000 for cervical cancer range from 83.2 in Recife, Brazil to 3 for non-Jews in Israel.

In Singapore the age-standardised rates per 100,000 per year has declined from 18.1 between the years 1968-72 to 10.6 between the years 1998-02. Although the incidence has declined over the years, cervical cancer, which is a preventable cancer, is still the second most common gynaecological cancers in Singapore.

In countries where cytological screening is not widely available, cervical cancer remains common. Worldwide, it is the second most common cancer among women, the third most common cause of cancer-related death, and the most common cause of mortality from gynaecological malignancy.

The primary goal of cervical cancer screening is to prevent cervical cancer. Cervical cytology screening is, in many respects, the ideal screening test. Cervical cancer has a defined premalignant phase of many years, which allows repeated tests to significantly reduce the impact of individual false-negative tests results. Cervical cytology is inexpensive and is readily accepted amongst women. However, it is a well-established fact that to be successful in population-based cervical screening, the coverage of the population screened must be adequate. Our efforts to educate women especially the high risk ones to come forth for screening must continue.

In some cases however, cervical cancer is undetected despite a recent screening test because of errors in sampling, interpretation, or follow up. Many methods to refine and improve cervical cytology have been proposed. In the 1980s, new devices were developed for enhancing the collection of exfoliated cells from the cervix. These include nylon brushes for sampling the endocervix and “broom” sampling devices, which simultaneously sample both the ectocervix and the endocervix.

Cervical cytology is the basis of the most effective and cost-effective cancer screening program ever implemented. Cervical cytology however is not a diagnostic test. In its attempt at improving the sensitivity of the test, liquid-based cervical cytology (LBC) has been introduced. In this method samples are collected in the usual manner from the cervix but are then transferred directly into the fixative solution rather than dispersed on a slide.

The liquid is then passed through a filter and the cells are transferred to a slide as a monolayer. The slide is then processed like a conventional Pap test. The ability to interpret the slide is improved because the cells are more evenly distributed and there is less artifactual material such as blood and mucus, thus reducing the incidence of unsatisfactory reports. The ability to test LBC specimens for HPV DNA and other sexually transmitted organisms further enhances the clinical appeal of this technology. Although slide evaluation is then performed by cytotechnicians/cytologists, automated image analysis technology also may be used.

Real time screening for cervical cancer using an electronic device called the Truscan consists of applying a probe that analyses its electrical and optical properties of the cervix. This makes it possible to distinguish among normal cervix, precancer and cancer. The potential advantages are instant diagnosis, good acceptance and relatively low cost. This screening method is still being evaluated.

In recent years, molecular biology has firmly established a causal relationship between persistent infection with high-risk human papillomavirus (HPV) genotypes and cervical cancer. The prevalence of the virus in cervical cancer is as high as 99.7%. It is however too earlier to speculate on the role of HPV testing as a primary screening or even complementary screening tool for use in population-based screening programs.

Cervical neoplasia develops in susceptible individuals in response to infection with high-risk type of HPV (16, 18, 31, 33, 45). HPV infections are commonly acquired by young women, but in most they are cleared by the immune system within 1-2 years without producing neoplastic changes. The risk of neoplastic transformation increases in those women whose infection persists.

In Singapore, we recommend that all women who have ever had sexual intercourse to have their first Pap smear by the age of 25 years and they can be discharged from screening at 65 years of age if the smear taken at 65 years is negative and the previous smears were negative.

The optimal number of negative cytology test results needed to reduce the false-negative rate to a minimum has not been demonstrated. Several studies have showed that in an organized program of cervical cancer screening, annual cytology examinations offer little advantage over screening performed at 2-or 3-year intervals.

With the potential for call and recall in its CervicalScreen Program, Singapore has adopted the policy of a three-yearly interval. However, women who are infected with human immunodeficiency virus (HPV) and who are immunosuppressed (such are those who have received renal transplants) may require more frequent cervical cytology screening.

Conclusion
The traditional approach to screening and management of precancerous lesions of the uterine cervix is effective as a winning strategy to prevent cervical cancer, particularly when there is extensive coverage of the screened population, and when a quality assurance procedure is an integral part of the program. Truly cervical cancer is a most preventable malignancy and death from cervical cancer is death from neglect.

 

Tew-Hong, Ho
Clinical Associate Professor
Head & Senior Consultant
Department of Obstetrics & Gynaecology, Singapore General Hospital
Chief of Gynaecology, KK Women’s and Children’s Hospital
Visiting Consultant, National Cancer Centre, Singapore