Related Pages Cancer Advances In Focus Index 1

Yesterday

• As recently as the 1940s, invasive cervical cancer was a major cause of death among women of childbearing years in the United States. However, with the introduction of the Papanicoloau (Pap) smear in the 1950s—a simple test that uses exfoliated cells to detect cervical cancer and its precursors—the incidence of invasive cervical cancer declined dramatically. Between 1955 and 1992, cervical cancer incidence in this country declined by 74%.
• Although epidemiologic evidence long suggested an association between sexual behavior (e.g., age at first intercourse, number of sexual partners) and cervical cancer, scientists and clinicians did not know the underlying reason for this link.
• In the early 1970s, cervical cone biopsy and hysterectomy were the mainstays of treatment. Clinical researchers were only beginning to develop and test more moderate procedures, such as cryosurgery, for treating preinvasive disease.

Today

• Cervical cancer—once one of the most common cancers affecting U.S. women—now ranks 14th in frequency in this population. In 2007, an estimated 11,150 women in the United States will be diagnosed with cervical cancer, and an estimated 3,670 will die of this disease. The lifetime risk of cervical cancer would be an estimated 3.7% in the absence of cervical cancer screening.
• In certain populations and geographic areas of the United States, cervical cancer death rates are still high, in large part due to limited access to health care and cervical cancer screening. Worldwide, especially in middle and low income countries, cervical cancer is the second most common cancer in women, and the third most frequent cause of cancer death, accounting for nearly 300,000 deaths annually.
• In 1996, the U.S. Food and Drug Administration (FDA) approved the use of the first liquid-based, thin-layer slide preparation as an alternative to the conventional Pap smear. This new technique separates cells from background material and provides a thin layer of cells for analysis. Various studies have suggested that liquid-based cytology is more sensitive than standard Pap smears in detecting cervical cancers and precancerous cellular abnormalities.
• Research conducted by the National Cancer Institute (NCI) and other investigators throughout the 1980s and 1990s demonstrated that virtually all cases of cervical cancer are caused by persistent infection with specific types of human papillomavirus (HPV), which can be transmitted by sexual contact. There are more than 100 types of HPV. Of the 15 types that are considered to be cancer-causing, or oncogenic, HPV types 16 and 18—which were first identified and molecularly cloned by researchers at the German Cancer Research Center—are responsible for about 70% of cervical cancers worldwide. In most women infected with HPV, however, the infection will resolve and cervical cancer will not develop; therefore, HPV infection is necessary but not sufficient for development of the disease.
• Highly-sensitive and specific molecular techniques for identifying HPV DNA in cervical specimens are now available. The current FDA-approved HPV DNA test can identify 14 of the high-risk strains associated with cell changes in the cervix. The NCI-supported ASCUS/LSIL Triage Study (ALTS) found that HPV DNA testing is sensitive in detecting underlying serious abnormalities among women with a Pap test diagnosis of ASCUS, or Atypical Squamous Cells of Undetermined Significance. An ASCUS result is considered to be borderline or ambiguous. The HPV DNA test can help to identify women who need further medical attention. The FDA has approved HPV testing, in conjunction with cytology, for screening women 30 years of age and older. If both tests are negative, screening is not repeated for 3 years.
• In June 2006, the FDA approved the vaccine Gardasil®, which is highly effective in preventing persistent infections with HPV types 16 and 18, two "high-risk" virus types that cause the majority of cervical cancers. Gardasil also protects against HPV types 6 and 11, which cause about 90% of genital warts. The vaccine is based on technology developed by NCI scientists, whose work laid the foundation for the production of HPV "virus-like particle," or VLP, vaccines. Using genetic engineering techniques to manipulate the genetic material of the virus, scientists created a vaccine consisting of non-infectious VLPs formed by a single protein—the L1 protein—from the outer surface of HPV. The L1 protein triggers a robust antibody response that neutralizes HPV infection. Gardasil is comprised of a mixture of HPV type 6, 11, 16, and 18 VLPs. Studies to date have shown that this vaccine provides protection against HPV 16 infection for at least 4 years. The vaccine is approved for use in females 9-26 years of age, but is most effective if given before the onset of sexual activity.
• Treatment for cervical cancer has improved considerably. The 5-year survival rate for women diagnosed with cervical cancer is close to 75%. Most cervical cancer patients receive radiation as part of their treatment. In addition, recent studies have demonstrated the value of chemotherapy treatment. Five large, randomized clinical trials found that chemotherapy administered with radiation therapy decreased the risk of death from cervical cancer by 30% to 50%, supporting the use of concomitant chemotherapy with radiotherapy for advanced disease. Cisplatin is the most common chemotherapy agent for cervical cancer.

Tomorrow

• Research on HPV vaccines is continuing. Cervarix™ (not approved for use in the United States), a second vaccine for preventing HPV infection, is in the late stages of clinical testing. This candidate vaccine is also based on the technology developed by NCI scientists. Initial studies of this vaccine—which also targets HPV types 16 and 18—have shown that Cervarix protects against persistent infection with these two HPV types, and may also confer some protection against very closely related HPV types. An NCI-sponsored Phase III clinical trial under way in Costa Rica—where HPV infection is particularly high—is evaluating the safety, efficacy, and other performance characteristics of Cervarix. The approximately 7,500 women participating in this trial will be followed for at least 4 years.

• Although Cervarix and Gardasil protect against infection with HPV types 16 and 18, these vaccines do not protect against HPV types found in approximately 30% of cervical cancers. Including VLPs from other oncogenic types of HPV in the vaccines is one approach to increase protection against the other viruses. In an alternative approach, researchers are now working to develop a vaccine targeted against a minor surface protein of HPV, known as L2, which contains regions that induce neutralizing antibodies against a broad range of HPV types. This property means that a single vaccine targeting the L2 protein may have the potential to provide broad protection against many HPV types.
• Studies of other experimental vaccines for treating HPV infection also are under way. Many of these experimental vaccines target two HPV oncogenic proteins, E6 and E7, which play an important role in inducing and maintaining cellular transformation.
• Scientists are striving to better understand why HPV infections resolve in most women but persist in others and lead to cervical cancer in only some women with persistent infections. Efforts to characterize the molecular pathways in cervical cancer cells, and to better understand how the interplay between these cells and their microenvironment may affect cancer development and progression, should provide critical insights.

• NCI's Centers for Population Health and Health Disparities are supporting research to understand and reduce differences in health outcomes, access, and care. Some studies are focused on increasing early detection of cervical cancer in women who live in the Appalachian region of the United States—where limited access to care may account for higher rates of cervical cancer incidence.

• NCI is also supporting efforts to make cervical cancer screening and treatment more affordable to help reduce the incidence of cervical cancer in developing nations—where 80% of cervical cancer occurs.

Glossary Terms

Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).

A process in which anything complex is separated into simple or less complex parts.

A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

The lower, narrow end of the uterus that forms a canal between the uterus and vagina.

Treatment with drugs that kill cancer cells.

A drug used to treat many types of cancer. Cisplatin contains the metal platinum. It kills cancer cells by damaging their DNA and stopping them from dividing. Cisplatin is a type of alkylating agent. Also called Platinol.

Occurring or existing at the same time as something else. In medicine, it may refer to a condition a person has or a medication a person is taking that is not being studied in the clinical trial he or she is taking part in.

Surgery to remove a cone-shaped piece of tissue from the cervix and cervical canal. Cone biopsy may be used to diagnose or treat a cervical condition. Also called conization.

A procedure in which tissue is frozen to destroy abnormal cells. This is usually done with a special instrument that contains liquid nitrogen or liquid carbon dioxide. Also called cryoablation and cryosurgical ablation.

The study of cells using a microscope.

The process of identifying a disease, such as cancer, from its signs and symptoms.

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered experimental in other diseases or conditions. Also called investigational.

An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The FDA also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called Food and Drug Administration.

An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called FDA.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

Refers to the genitalia (external and internal sex organs and glands).

A type of virus that can cause abnormal tissue growth (for example, warts) and other changes to cells. Infection for a long time with certain types of HPV may cause cervical cancer. HPV may also play a role in some other types of cancer. Also called human papillomavirus.

A type of virus that can cause abnormal tissue growth (for example, warts) and other changes to cells. Infection for a long time with certain types of human papillomavirus may cause cervical cancer. Human papillomavirus may also play a role in some other types of cancer. Also called HPV.

Surgery to remove the uterus and, sometimes, the cervix. When the uterus and the cervix are removed, it is called a total hysterectomy. When only the uterus is removed, it is called a partial hysterectomy.

The number of new cases of a disease diagnosed each year.

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

Cancer that has spread from the surface of the cervix to tissue deeper in the cervix or to other parts of the body.

A condition in which the cells of the uterine cervix are slightly abnormal. LSIL is not cancer. Also called low-grade squamous intraepithelial lesion.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. It conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://www.cancer.gov. Also called National Cancer Institute.

A procedure in which cells are scraped from the cervix for examination under a microscope. It is used to detect cancer and changes that may lead to cancer. A Papanicolaou test can also show conditions, such as infection or inflammation, that are not cancer. Also called Pap smear and Pap test.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant.

In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. The survival rate is often stated as a five-year survival rate, which is the percentage of people in a study or treatment group who are alive five years after diagnosis or treatment. Also called overall survival rate.

In medicine, the change that a normal cell undergoes as it becomes malignant.

A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.

In medicine, a very simple microorganism that infects cells and may cause disease. Because viruses can multiply only inside infected cells, they are not considered to be alive.

A raised growth on the surface of the skin or other organ.