Information about the prevention of cancer and the science of screening appropriate individuals at high-risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best "treatment" of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable. Cervical cancer accounts for 6% of all cancers in women, with an estimated 16,000 new cases and 5,000 deaths in the United States each year. Widespread use of a screening test called the Pap smear has led to a decline in the number of deaths resulting from cervical cancer. Continued progress and education about screening may allow for earlier detection and higher cure rates.

The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person´s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer.

Heredity or Genetic Factors

At this time, researchers have not identified any genetic factors that contribute to the development of cervical cancer.

Environmental or Non-Genetic Factors

Several risk factors have been associated with an increased risk of developing cervical cancer. These include early age at first intercourse (16 or younger), history of multiple sexual partners, smoking, and poor nutrition. In addition, a history of sexually transmitted diseases, such as chlamydia, human papillomavirus (HPV) and human immunodeficiency virus (HIV) appear to increase the risk of developing cervical cancer. Human Papillomavirus (HPV): The human papillomavirus is a sexually transmitted disease that is the primary cause of cervical cancer. HPV is present in virtually all cases of invasive cervical cancer. It is estimated that more than 6 million women in the United States have HPV infection. There are more than 100 types of HPV and over 30 of these can be transmitted through sexual contact. Different types of HPVs are classified as "low-risk" and "high-risk". While both low-risk and high-risk HPVs can cause the growth of abnormal cells, usually only the high-risk HPVs will develop into cancer. There are 13 types of HPV known to be associated with cervical cancer that are classified as high-risk. Only a small percentage of individuals who develop high-risk HPV infections will later develop cervical cancer. While HPV infection is one factor in the development of cervical cancer, researchers believe that a variety of factors work together to contribute to this development.

Chlamydia: Chlamydia is the most common sexually transmitted disease in the U.S. Results from a study performed in Scandinavia indicated that women with any type of chlamydia infection were 2.5 times more likely to develop cervical cancer than women who had no evidence of chlamydia infection. Moreover, women with a particular subtype of chlamydia, serotype G, were 6 times more likely to develop cervical cancer.

Human Immunodeficiency Virus (HIV): Women who are infected with HIV are at a high risk of contracting HPV as a result of immunosuppression and possibly risky sexual practices. HPV infections are recognized as the primary cause of cervical cancer, but often women will have coinfection with both HPV and HIV.

Prevention

Cancer is largely a preventable illness. Two-thirds of cancer deaths in the U.S. can be linked to tobacco use, poor diet, obesity, and lack of exercise. All of these factors can be modified. Nevertheless, an awareness of the opportunity to prevent cancer through changes in lifestyle is still under-appreciated.

Cervical cancer is one of the more preventable types of cancer. The two best ways to reduce the risk of developing cervical cancer are to avoid the risk factors and to receive an annual screening exam. As several sexually transmitted diseases have been associated with the development of cervical cancer, the prevention of these diseases may play a crucial role in reducing the risk of cervical cancer. Women are advised to delay sexual activity, limit the number of sexual partners and to protect themselves from sexually transmitted diseases.

Diet: Diet is a fertile area for immediate individual and societal intervention to decrease the risk of developing certain cancers. Numerous studies have provided a wealth of often-contradictory information about the detrimental and protective factors of different foods.

There is convincing evidence that excess body fat substantially increases the risk for many types of cancer. While much of the cancer-related nutrition information cautions against a high-fat diet, the real culprit may be an excess of calories. Studies indicate that there is little, if any, relationship between body fat and fat composition of the diet. These studies show that excessive caloric intake from both fats and carbohydrates lead to the same result of excess body fat. The ideal way to avoid excess body fat is to limit caloric intake and/or balance caloric intake with ample exercise.

There is convincing evidence that excess body fat substantially increases the risk for many types of cancer. While much of the cancer-related nutrition information cautions against a high-fat diet, the real culprit may be an excess of calories. Studies indicate that there is little, if any, relationship between body fat and fat composition of the diet. These studies show that excessive caloric intake from both fats and carbohydrates lead to the same result of excess body fat. The ideal way to avoid excess body fat is to limit caloric intake and/or balance caloric intake with ample exercise.

It is still important, however, to limit fat intake, as evidence still supports a relationship between cancer and polyunsaturated, saturated and animal fats. Specifically, studies show that high consumption of red meat and dairy products can increase the risk of certain cancers. One strategy for positive dietary change is to replace red meat with chicken, fish, nuts and legumes.

High fruit and vegetable consumption has been associated with a reduced risk for developing at least 10 different cancers. This may be a result of potentially protective factors such as carotenoids, folic acid, vitamin C, flavonoids, phytoestrogens and isothiocyanates. These are often referred to as antioxidants. Several studies have suggested that beta carotene, vitamin C and vitamin E may reduce the risk of developing cervical cancer.

There is strong evidence that moderate to high alcohol consumption also increases the risk of certain cancers. One reason for this relationship may be that alcohol interferes with the availability of folic acid. Alcohol in combination with tobacco creates an even greater risk of certain types of cancer.

Exercise: Higher levels of physical activity may reduce the incidence of some cancers. According to researchers at Harvard, if the entire population increased their level of physical activity by 30 minutes of brisk walking per day (or the equivalent energy expenditure in other activities), we would observe a 15% reduction in the incidence of colon cancer.

Screening and Early Detection

For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for that cancer. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection, and treatment strategies.

All women are advised to receive regular gynecological exams at the onset of sexual activity or by the age of 18. Gynecological exams should include both a manual pelvic exam and a Pap smear. Regular surveillance can increase the possibility that cancer could be found at an early stage when treatment is most likely to produce a cure.

Papanicolaou (Pap) Smear: The Pap smear is one component of the annual gynecological exam. Routine screening with a Pap smear is used to detect cancerous cells in the cervix early, as well as to detect abnormal cells in the cervix before they become cancerous. During a Pap smear, a sample of cells from the cervix is taken with a small wooden spatula or brush and examined under the microscope.

The results of the Pap smear are classified into five categories: negative or within normal limits (normal); atypical squamous cells of undetermined significance (ASCUS); low-grade squamous intraepithelial lesions (abnormal); high-grade squamous intraepithelial lesions (abnormal); or carcinoma (cancer).

If the results are normal, no further evaluation is necessary. Women who have normal results will simply need to continue receiving an annual examination and Pap smear.

Abnormal results from a Pap smear do not necessarily indicate cancer. Other conditions such as inflammation and sexually transmitted diseases can cause abnormal changes in cells. Some women will exhibit mild dysplasia (abnormal cells), in which case they may need to schedule frequent Pap smears to monitor for any changes. Women with severe dysplasia may need to undergo a biopsy for closer examination of abnormal tissue.

Often, when the results are not clear, women will be asked to repeat a Pap smear. Sometimes, when results show cells that are clearly abnormal, but not yet cancerous, more diagnostic procedures are done and, if needed, treatment is provided to prevent cancer from developing.

Hybrid Capture II HPV: When the results of the Pap smear are categorized as ASCUS, doctors cannot determine whether the cells are likely to progress into cancer or not. The Hybrid Capture II HPV test can sometimes help determine whether treatment is necessary for women with ASCUS results. The Hybrid Capture II HPV test is a new DNA-based test designed to detect the 13 types of HPV that are associated with cervical cancer, a function that the Pap smear does not provide. Women with a Pap smear identified as ASCUS can undergo additional testing with the HPV test to determine whether any cancer-associated HPV cells are present. An ASCUS Pap smear and the detection of a high-risk HPV type would suggest the presence of high-risk precancerous cells, requiring further diagnostic testing. Alternatively, an ASCUS Pap smear and detection of a low-risk HPV type would suggest the presence of cells that are less likely to progress to cancer.

Several other screening procedures exist that are more invasive and can be used to determine the significance of abnormal Pap smear results. These procedures are not routine screening procedures, but are used for diagnosis and sometimes as treatment for dysplasia.

Colposcopy and Punch Biopsy: After abnormal results from a Pap smear, an HPV test, or both, a physician may opt to perform a colposcopy. During a colposcopy, a physician uses a special microscope called a colposcope to better visualize the cervix. The physician then applies a special solution to the cervix that makes abnormal cells appear white, while normal cells appear pink. The physician then performs a punch biopsy (also referred to as a cervical biopsy) and removes a tiny sample of abnormal tissues in order to evaluate the cells under a microscope.

Endocervical Curettage: This procedure may be performed at the same time as the punch biopsy, especially if there is concern that there may be abnormal tissue past the opening of the cervix that cannot be seen with the colposcope. During an endocervical curettage, a small spoon-shaped instrument called a curette is used to scrape cells away from inside the endocervical canal. These cells are then sent to the lab for examination under a microscope.

Conization: If the information obtained from colposcopy, biopsy and/or curettage is inconclusive, a physician might perform a conization. During a conization, or cone biopsy, the physician removes a cone-shaped sample of tissue from the cervical canal. The sample is then sent to the lab for examination. Conization can also serve as the primary treatment of precancerous cervical cancer, as a large sample is removed and can sometimes remove any cancerous tissue in the process. This is a fairly intrusive procedure and can involve significant complications.

Loop Electrosurgical Excision Procedure (LEEP): Loop electrosurgical excision procedure (LEEP), also called large loop excision of the transformation zone (LLETZ), is simpler and less invasive than conization. Some physicians believe that this procedure will replace conization, while others disagree. During LEEP, a physician applies a local anesthetic to the cervix and then inserts a wire loop into the vagina. A high frequency electrical current is run through the wire to remove abnormal tissue from both the cervix and the endocervical canal. Like conization, LEEP can be used not only as a diagnostic tool, but also as treatment, as large and deep sections of abnormal tissue can be removed.

Dilation and Curettage (D and C): Infrequently, it may still remain unclear whether the abnormal cells detected from a Pap test are confined to the cervix or arise from inside the uterus. In this situation, a D and C may be recommended. During a D and C, the cervical opening is dilated (stretched) and a curette is inserted to remove cells from the lining of the uterus and cervical canal.

Strategies to Improve Screening and Early Detection

The potential for earlier detection and higher cure rates increases with the advent of more refined screening techniques. In an effort to provide more screening options and perhaps more effective prevention strategies, researchers continue to explore new techniques for the screening and early detection of cancer.

Some new strategies for the screening of cervical cancer have recently emerged. Despite progress in this area, it is still important that women continue to utilize the standard screening procedures in an effort to maintain their health and detect cervical cancer early when it is most treatable. However, these new procedures hold promise for earlier and more reliable detection of cervical cancer and some women may be interested in participating in clinical trials that will help to determine the effectiveness of these new techniques.

ThinPrep Pap Test: The ThinPrep Pap Test improves upon the conventional Pap smear by improving the way the sample is prepared. With the ThinPrep Pap Test, the physician uses the same procedure as the conventional Pap smear to collect a sample from the patient, but then rinses the collection device into a vial of preserving solution, thereby capturing the entire sample. The vial is then sent to the laboratory, where an instrument called the ThinPrep 2000 processor disperses and filters the contents to reduce blood, mucus and inflammation. This instrument then deposits a thin, even layer of cervical cells onto a slide. This slide contains a more uniform sample of well-preserved cells than that offered by the traditional smear method.

In clinical trials, the ThinPrep Pap Test reduced the number of inadequate samples by more than 50%. In addition, results from the clinical trials indicate that the test is 65% more effective in detecting cancerous and precancerous lesions.

The ThinPrep Pap Test received FDA approval in the spring of 2000 and is becoming increasingly available at medical centers nationwide. The test will initially cost a few more dollars than the conventional method, but researchers predict that it will eventually save the healthcare system hundreds of thousands of dollars by detecting cervical cancer earlier, when it is most treatable. In addition, the improved quality of samples will reduce the number of unnecessary repeat tests.

Vaccines: As the human papillomavirus (HPV) is the primary cause of cervical cancer, the development of a vaccine to prevent HPV could also prevent cervical cancer. A vaccine, HPV16 L1 VLP, has been developed against HPV16. In early trials, the vaccine was shown to be safe and produced an immune response that was 40 times higher than the response produced by natural infection. These results prompted researchers to initiate a phase II trial of the vaccine. More research is needed before vaccines become widely available, but vaccines show promising potential in the prevention of cervical cancer.

HPV Test: Recent research indicates that the Hybrid Capture II test for the human papillomavirus (HPV) may be a valuable diagnostic tool in women whose Pap smear results are classified as atypical squamous cells of undetermined significance (ASCUS). A multi-center clinical trial compared three management strategies following an ASCUS diagnosis.

The study involved 3,488 women who had a recent diagnosis of ASCUS. The women were randomized to receive one of three follow-up options: immediate colposcopy, Hybrid Capture II HPV test, or a follow-up Pap smear. If the follow-up Pap smear indicated high-grade squamous intraepithelial lesions or the results of the HPV test were positive, then these women were referred to colposcopy.

The results indicated that the HPV test was an effective next-step following an ASCUS diagnosis. In this study, 55% of women with ASCUS tested positive for HPV and would be referred to colposcopy using this management strategy. About 5% of the women in the trial were diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3), which is a lesion at high risk of progressing to invasive cancer. Of these women, 96.3% tested positive for HPV. The results also indicated that the HPV test in women with ASCUS results has a negative predictive value of 99.5%, so the 45% of women who were HPV-negative are highly unlikely to have a significant abnormality.

The results of this study make a strong case for using the Hybrid Capture II HPV test as an intermediate step following an ASCUS diagnosis, but prior to performing a colposcopy. By reducing the number of women referred to colposcopy, this triage strategy could help to reduce the medical costs of performing more invasive procedures and spare healthy women from undergoing unnecessary procedures.

Veda-Scope: A new device developed in Australia, the Veda-Scope, could potentially replace the traditional speculum and make Pap smears more comfortable. The Veda-Scope uses a combination of air pressure and fiber optics to visualize the cervix. The device operates through a filtered air pump that inflates the vagina and allows the physician to view the cervix. It has a fiber-optic head that provides internal illumination of the cervix and can magnify up to six times. The Veda-Scope also has a 4 cm single-use disposable speculum with a soft foam cup and a brush pushed into the speculum for taking samples.

Researchers from the Sydney Center for Reproductive Health (SCRH) and the University of Sydney surveyed 120 women and found that 94% thought that the Veda-Scope was more comfortable than the traditional bi-valve speculum. Because the Veda-Scope is more comfortable, it could lead to an increase in the number of women who undergo screening with Pap smears.