Worldwide, there were approximately 493,243 new cases, and 273,505 deaths attributed to cervical cancer in 2002, which is about one-tenth of total female cancer deaths 1. Cervical cancer incidence 2, and mortality in the United States has declined significantly since the 1950's by more than 70% 3,4. This decline is mainly attributed to the introduction of the Papanicolaou test in the 1940's. Cervical cancer which in this country was the number one killer of women, is now ranked 12th in cancer deaths for women in the US 5,6. In the US, it is estimated that 11,150 women will be diagnosed with cervical cancer, and approximately 3,670 will die of it. However, cervical cancer is the second most frequent of all female malignancies worldwide, with 80% of the cases occurring in resource-poor countries 7. While in the United States and most developed countries, cervical cancer accounts for 7% of all female malignancies, in developing countries, it accounts for 24% of all such cancers 1. This disparity is primarily attributed to the lack of screening and treatment of pre-cancerous lesions 1.
The anatomical accessibility of the cervix to direct examination, with a long preclinical stage during which precursor lesions can be treated conservatively and successfully (~95%) 8, make cervical neoplasia ideal for secondary prevention efforts such as screening. The Pap smear test is probably the most widely used cancer screening test, even though it has never been evaluated in a randomized controlled trial, and will not be because it is been accepted as an effective screening tool. Additionally there are numerous convincing epidemiological data which show that since the introduction of Pap in countries with well organized screening programs, and with wide population coverage, both incidence of, and mortality from cervical cancer has significantly decreased. The best data to support these observations come from Nordic countries. Incidence of cervical cancer has fallen by more than 50% in Finland, Sweden, Denmark, and Iceland, where organized cervical screening programs were established in the 1960s 9. Interestingly, despite the availability of a Pap screening program in England, cervical cancer incidence remained relatively constant, until the introduction of an organized screening program in 1988, which led to a dramatic reduction in subsequent years 9.
Since the introduction of organized cervical screening in the 1960's in the U.S., incidence and mortality from cervical cancer have declined by 75%, however, this decline is not uniform. In the 1990s U.S. women experienced at least 33% higher incidence of, and 71% higher mortality from cervical cancer in high poverty counties than in low poverty counties 10. The Healthy People 2010 objective of 90% Pap screening for women aged 18 or older has not yet been achieved by any State or territory 11. Unscreened populations of women in the U.S. historically include older women, uninsured and impoverished women, migrant and minority women, and those residing in rural areas 12. Data from the 1994 and 2003 U.S. National Health Interview Survey showed that screening trends have remained unchanged from the 1994 survey to the 2003 survey - 77% and 76% of women reported having had a Pap test in the past 3 years, respectively 13,14. Additionally, they show that age is still a risk factor for inadequate screening; in the 1994 survey screening was higher among 18-44 year old women (82%) compared to 57% among women 65 or older. This age difference may be due to a cohort effect. Pap testing was still gaining acceptance in the late 1950's and 1960's. Women who were in the reproductive age group at that time (and are now over 65 years) never became accustomed to regular cytology screening. This trend remained virtually unchanged in the 2003 survey; 81% of the 18-44 and 57% of 65 or older women had a Pap in the previous 3 years. The 2003 survey showed that while screening rates among African-Americans and Whites were similar, screening rates were much lower in other race groups (76%, 80%, and 69% for Whites, African-Americans, and other race groups, respectively).
Organizing screening programs in developing countries where the burden of cervical cancer is the greatest has remained a challenge. There are many obstacles to cervical cancer screening in resource poor countries, generally attributed to a lack of infrastructure and resources – technical, medical, and financial - and a lack of awareness and education about cervical cancer among women and health-care providers. Moreover, in Africa and South America which bear the biggest cervical cancer burden, there are competing health care needs such as HIV/AIDS, infectious diseases such as malaria, tuberculosis, and high infant and maternal mortality rates. In addition there are not many trained clinicians, and there is a lack of adequate laboratory supplies and personnel, and treatment facilities 5. We refer interested readers to an excellent review specific to this topic 15.
Furthermore, there are considerable cultural barriers to routine pelvic screening, especially in the absence of any symptoms, underscoring the profound need for an acceptable and reliable screening method that focuses on timely detection of early lesions, and treatment of the lesions so as to reduce cervical cancer burden. Although cytology has proven to be extremely effective in detection of abnormal cervical cells in developed countries, it is still under-utilized by many even in regions with successful screening programs. An important aspect of the success of cytology screening in developed countries is attributed to repeated screening of women during the long natural history of cervical cancer development. The repeated nature of the screening makes it cost-prohibitive for resource-poor countries. Moreover, the need for multiple visits – one to perform the test, a second to obtain results, and a possible third for treatment – can lead to loss of follow-up of women who may be at greatest risk of cervical cancer, further compounding a complex issue. Screening programs in resource-poor settings must consider these limitations and develop approaches sustainable and suitable for those settings such considering screening methods that target the etiologic agent HPV, appropriate age to initiate screening, and screening interval, and one designed to encompass screening and treatment at one time.
A range of abnormal cellular changes occur in the transformation zone of the cervical epithelium. There are two embryologically distinct cell types that make up the cervical epithelium. 1) The ectocervix, the part of the cervix that extends into the vagina, is made of nonkeratinized stratified squamous epithelium, similar to the lining of the vagina; 2) the endocervix, the part of the cervix that leads to the uterus, is made of mucus secreting, columnar epithelium 16. The junction of the columnar and the stratified squamous epithelial cells is called the squamocolumnar junction, which recedes towards the endocervix with age, replacing columnar cells with stratified squamous epithelium. This process is called squamous metaplasia, and leads to the formation of the ‘transformation zone’ from the original squamocolumnar junction to the current squamocolumnar junction. Due to the rapid turn over of cells in the transformation zone, it is very susceptible to carcinogens and carcinogenesis, and HPV infections. Most precancerous cervical lesions and cancers arise in the transformation zone. Approximately 75 to 80% of all cervical cancers are squamous cell carcinoma (SCC) 17. Adenocarcinomas account for the remaining 25%.