RxPG News : Cervical Cancer

New vaccine prevents cervical cancer in teens

Sat, 01 Jul 2006 15:57:37 PST

( from http://www.rxpgnews.com ) New research reported in the June issue of Clinical Pediatrics suggests that the possibility of preventing cervical cancer and other cancers caused by the human papilloma viruses (HPVs) will be a reality in the near future. Two new vaccines, one developed by Merck (approved in June 2006) and one developed by Smith Glaxo Kline (likely to be approved soon), target types of HPV known to have a link to cervical and other cancers. The new vaccines prevented the disease or reduced infection in over 90% of cases and was well tolerated.

In the past 20 years, advances in cellular, molecular and immunologic technologies have contributed to the discovery of the link between HPV and cervical cancer. Two types, HPV 16 and HPV 18 account for the development of 70% of all cervical cancer cases. Other types of HPV cause other types of cancers, including some vulvar and vaginal cancers in women and penile cancers in men. Approximately 50% of all sexually active women are infected with one or more high risk HPV types, and by age 50 at least 80% of women will have acquired genital HPV infection. Approximately 74% of new HPV infections occurred among individuals 15-24 years old.

Researchers at Harvard School of Public Health developed a computer-based model of various cancer-prevention policies and their research suggests that the most cost-effective approach would be to administer the vaccine to young girls starting at the age of 11-12 with conventional pap smears for cervical abnormalities beginning at a later age and less frequently than currently recommended.. This model suggests that the absolute lifetime risk of cervical cancer would be reduced by 94 percent compared to no intervention at all.

"The possibility of preventing cervical cancer is both exciting and challenging," writes author Michael E Pichichero, MD, in the article. "HPV vaccination would produce health gains that would be worth the cost."

Topotecan for Late-Stage Cervical Cancer Approved

Fri, 16 Jun 2006 00:44:37 PST

( from http://www.rxpgnews.com ) The U.S. Food and Drug Administration has approved a combination of Topotecan hydrochloride and cisplatin for use as the first drug treatment for women with late-stage cancer of the cervix when a physician determines that surgery or radiation therapy are unlikely to be effective. The approval includes a new indication for Hycamtin, which was approved in 1996 for treating ovarian cancer and in 1998 for small cell lung cancer.

In the United States there are an estimated 10,000 new cases of cervical cancer and about 3,700 related deaths each year.

"We are making great strides in the fight against cervical cancer, a disease that, world wide, is the second most common cancer in women," said Dr. Andrew von Eschenbach, Acting FDA Commissioner. "This course of drug therapy is a potentially life-prolonging option for thousands of women."

The combination of Hycamtin and cisplatin is specifically indicated for women with Stage IVB (incurable), recurrent, or persistent cancer of the cervix which spreads to other organs and is not likely respond to treatment with surgery or radiation.

In clinical trials involving this patient population, 293 patients were randomized to Hycamtin plus cisplatin or to cisplatin alone. Most of the participants had received prior radiation therapy as the standard treatment, while some may have undergone prior surgery. The combination therapy significantly improved survival compared to the use of cisplatin alone. Patients on combined therapy survived (9.4 months), about three months longer than patients on cisplatin alone (6.5 months).

Hycamtin is associated with a significant risk of neutropenia (a drop in white blood cell count), a condition which makes it more difficult for the body to fight infections. Serious side effects also include thrombocytopenia, a decrease in blood platelets that can lead to excessive bleeding and anemia. Less serious side effects include nausea and vomiting. The incidences of neutropenia, anemia, and thrombocytopenia were significantly increased among patients receiving the combination treatment compared to those receiving cisplatin alone, as were nausea and vomiting, mucositis, rash, and liver toxicity.

New HPV vaccine is 100 percent effective

Sat, 10 Jun 2006 13:28:37 PST

( from http://www.rxpgnews.com ) More than twenty years of collaborative research in the Georgetown lab of Dr. Richard Schlegel has resulted in a major medical breakthrough the worlds first cancer vaccine.

The vaccine's technology was generated by a team of Georgetown University researchers in the early 1990s and licensed for commercial development. On June 8, the Food and Drug Administration approved the vaccine, which scientists say could eliminate most new cases of cervical cancer worldwide. Called Gardasil, the vaccine blocks four strains of HPV, including two that give rise to nearly 75 percent of cervical cancer cases and two other strains that cause about 50 percent of genital warts.

Its a researchers dream to see something that started as a very cerebral idea in the laboratory to advance through animal and clinical trials, gain FDA approval and ultimately have a major global impact, Schlegel said. Its highly unlikely but extremely gratifying to see it through so far.

Schlegel, professor and chair of Georgetowns Department of Pathology, in the Lombardi Comprehensive Cancer Center, began a research project in the late 1980s studying the molecular biology of the human papillomavirus (HPV), the precursor to most cervical cancers. Looking at the biological makeup of the virus through an advanced microscope, Schlegel said he never imagined he was laying the groundwork for something that could change the face of global medicine.

Instead, he focused on the millions of people worldwide infected with the sexually transmitted disease, particularly those in developing countries where HPV strikes 400,000 women annually. Without access to routine preventative care and annual Pap screening, HPV can develop into cervical cancer, the most common form of cancer and the leading cause of cancer deaths among women in developing nations.

We realized these deaths were largely preventable thats really all the motivation we needed, he said.

For the past two decades, Dr. Schlegel has been a leader in improving public health for men, women and children around the world, said Stuart Bondurant, MD, interim executive vice-president for health sciences at Georgetown University Medical Center. His important work to develop a preventative cervical cancer vaccine will save millions of lives and is rooted in Georgetowns mission of service to others.

A cell biologist by training, Schlegel came to Georgetown from the National Institutes of Health in 1990 to join forces with immunology and pathology experts A. Bennett Jenson, PhD, and Shin-je Ghim, PhD, who were studying how cervical cancer originates after HPV infection. Together, the researchers based the vaccine on the protein that comprises the viruss outer shell. This protein stimulates an immune response in the body that attacks the virus, disabling it before reproduction and infection can occur.

At the time, Georgetown had one of the strongest HPV research programs of any institution in the country ... you couldnt have asked for a more capable team of people, Jenson said. We were the right group of people, at the right time, with the right stars shining in our direction.

Ghim remembers that once the three researchers began working together, they knew they were on to something. Progress was slow at first, but we sensed it was coming. No one really believed in a vaccines ability to prevent cancer, she said.

They first tested the vaccine in dogs and found it was 100 percent effective in preventing HPV infection. From there, they licensed the technology to an external company to begin clinical trials, which showed that the vaccine also protected women from contracting the virus.

Once we were able to grow the virus [in cell cultures], things started happening quickly, he said. It didnt take long at all for the vaccine to move through trials and into the hands of the pharmaceutical companies.

The development and approval of this cervical cancer vaccine is a watershed moment in cancer research, said Anatoly Dritschilo, MD, interim director of Georgetowns Lombardi Comprehensive Cancer Center. This promising work will have a major impact on the incidence of cervical cancer here in the United States and around the world.

Vaccine for Cervical Cancer Approved in US - Overview

Fri, 09 Jun 2006 02:04:37 PST

( from http://www.rxpgnews.com ) FDA has now announced the licensure of Gardasil, the first vaccine for the prevention of cervical cancer, abnormal and precancerous cervical lesions, abnormal and precancerous vaginal and vulvar lesions and genital warts. Gardasil is a recombinant vaccine and is effective against HPV types 6, 11, 16 and 18, and is approved for use in females ages 9-26 years.

Recombinant vaccines are made by genetic engineering, the process and method of manipulating the genetic material of an organism. In this case, the genes that code for a specific protein from each of the four virus types of HPV are expressed in yeast to create large quantities of the protein. The protein that is produced is purified and then used to make the vaccine. Because the vaccine only contains a protein, and not the entire virus, the vaccine cannot cause the HPV infection. It is the body's immune response to the recombinant protein(s) that then protects against infection by the naturally occurring virus.

HPV is the name of a group of viruses that includes more than 100 different types. More than 30 of these viruses can be passed from one person to another through sexual contact. For most women, the body's own defense system will clear the virus and they don't develop health problems. However, some types can cause cervical cancer or abnormal cells in the lining of the cervix that can sometimes progress to cancer. Other types are a major cause of genital warts.

For women who do develop cervical cancer, HPV is generally the root cause. In 2006, it is estimated that there will be 9,710 new cases of cervical cancer and 3,700 deaths attributed to it in the United States. Worldwide, cervical cancer is the second most common cancer in women; and it is estimated to cause over 470,000 new cases and 233,000 deaths per year.

HPV is the most common sexually transmitted infection in the United States. The Centers for Disease Control and Prevention (CDC) estimates that about 6.2 million Americans become infected with genital HPV each year and that over half of all sexually active men and women become infected at some time in their lives.

The vaccine is effective against HPV types 16 and 18 which cause approximately 70% of cervical cancers, and against HPV types 6 and 11 which cause approximately 90% of genital warts.

Gardasil is expected to prevent up to 70% of cervical cancers, because they are due to HPV types against which the vaccine is directed. However, it does not protect against the types of HPV that are not included in the vaccine, which can also cause some cancers. Furthermore, women aren't protected if they have already been infected with the HPV types(s) that are covered by the vaccine prior to vaccination.

Since no vaccine is 100% effective and Gardasil won't provide protection against the HPV types not in the vaccine, or against existing HPV infections, routine Pap screening remains critically important to detect precancerous changes in the cervix to allow treatment before cervical cancer develops.

Four multinational studies were conducted to show how well Gardasil worked in women between the ages of 16 and 26 by giving them either the vaccine or placebo. The results showed that in women who had not already been infected with the type of HPV contained in the vaccine, Gardasil was nearly 100 percent effective in preventing precancerous cervical lesions, precancerous vaginal and vulvar lesions and genital warts caused by infection with the HPV types against which the vaccine is directed . It is believed that prevention of cervical precancerous lesions is highly likely to result in the prevention of those cancers.

Two studies were also performed to measure the immune response to the vaccine among younger females aged 9-15 years. Their immune response was similar to that found in 16-26 year olds, indicating that the vaccine should have similar effectiveness when used in the 9-15 year age group.

It is important to note that Gardasil did not protect against HPV types that are not in the vaccine.

Gardasil only works to prevent cervical cancer, precancerous genital lesions and genital warts due to human papillomavirus (HPV); it won't work as treatment.

In the studies, females with current or past infection with one or more vaccine-related HPV types prior to vaccination were protected from the diseases caused by the other remaining HPV types contained in the vaccine.

Gardasil is not approved for use in males, but the manufacturer currently has a study underway to see if it is safe and effective for them. Once the study is complete and submitted to FDA, the agency will review the data and decide whether to approve Gardasil for males.

Gardasil is given as three injections over a six-month period; the first dose is given at an initial time selected by the vaccine recipient and her healthcare practitioner, followed by another dose 2 months later, and the third and last dose, six months after the first dose. The vaccine is administered intramuscularly in the upper arm or thigh.

The results of the studies show that the vaccine only works when given prior to infection with HPV types 6, 11, 16 and 18.

FDA has approved Gardasil as safe and effective for use in females ages 9-26 years. Now that the vaccine has been licensed, CDC's Advisory Committee on Immunization Practices (ACIP) will discuss Gardasil at its June 29, 2006, meeting and make recommendations concerning its use.

More than 10,500 females who received Gardasil were evaluated for adverse reactions. Most of the reactions experienced by the study participants were not serious and included mild or moderate local reactions, such as pain or tenderness at the site of the injection. It is always possible that unexpected and rare adverse events can occur when a vaccine is used more widely. The manufacturer has committed to FDA to performing additional studies of the safety of Gardasil. In addition, FDA and CDC carefully monitor the safety of approved vaccine through the Vaccine Adverse Event Reporting System (VAERS) in order to detect any problems.

Females who are allergic to yeast or to any component of the vaccine should not receive Gardasil. FDA has approved Gardasil as safe and effective for use in females ages 9-26 years.

Gardasil is not a live virus vaccine; it does not contain the HPV virus and therefore, cannot cause the HPV infection. Gardasil does not contain thimerosal or any other preservative.

Quadrivalent Human Papillomavirus (HPV) Recombinant Vaccine Approved by FDA

Fri, 09 Jun 2006 00:36:37 PST

( from http://www.rxpgnews.com ) U.S. Food and Drug Administration (FDA) today approved a Quadrivalent Human Papillomavirus Recombinant Vaccine. It is the first and only vaccine to prevent cervical cancer and vulvar and vaginal pre-cancers caused by HPV types 16 and 18 and to prevent low-grade and pre-cancerous lesions and genital warts caused by HPV types 6, 11, 16 and 18 and is developed by Merck and will be marketed under trade name Gardasil.

The FDA approved Gardasil for the prevention of cervical cancer; cervical intraepithelial neoplasia (CIN) 2/3 and adenocarcinoma in situ (AIS), vulvar intraepithelial neoplasia (VIN) 2/3 and vaginal intraepithelial neoplasia (VaIN) 2/3 caused by HPV types 16 and 18. Gardasil is also approved for the prevention of genital warts and low-grade cervical lesions (CIN 1) caused by HPV types 6, 11, 16 and 18. Gardasil is approved for 9- to 26-year-old girls and women.

"Merck is proud to be the leader in cervical cancer vaccine research and development," said Richard T. Clark, chief executive officer and president, Merck & Co., Inc. "Bringing forward this life-saving scientific advance is yet another testament to Merck's long-standing mission to research and develop novel vaccines and medicines that can greatly improve public health."

Gardasil is designed to prevent the majority of HPV-related clinical diseases, those caused by HPV 6, 11, 16 and 18. HPV types 16 and 18 account for approximately 70 percent of cases of cervical cancer, AIS (non-invasive cervical cancer), CIN 3, VIN 2/3 and VaIN 2/3, and account for 50 percent of CIN 2 lesions. HPV 6 and 11 cause approximately 90 percent of genital wart cases. These four types of HPV also cause approximately 35 to 50 percent of all low-grade cervical, vaginal and vulvar lesions (CIN I, VIN I and VaIN I). There are an estimated 4.7 million abnormal Pap results that require follow-up each year in the United States. At least 3 million of these results are caused by some type of HPV. All four types cause abnormal Pap test results; the lesions caused by types 6 and 11 are clinically indistinguishable from pre-cancerous lesions caused by types 16 and 18.

"Gardasil is a major health breakthrough - the first vaccine specifically designed to prevent cancer - and is approved to prevent not only cervical cancer but also genital warts," said Kevin Ault, MD, associate professor, Department of Gynaecology and Obstetrics, Emory University School of Medicine, and clinical study investigator for Gardasil. "Use of Gardasil can help significantly reduce the human and economic burden of cervical cancer, pre-cancerous or low-grade lesions and genital warts caused by HPV 6, 11, 16 and 18 in the United States, and the rest of the world, in this generation and future generations."

In the United States, approximately 10,000 women are diagnosed with cervical cancer every year, and an average of 10 women die each day from the disease.

In clinical studies, Gardasil prevented 100 percent of HPV 16 and 18 related cervical cancer in women not previously exposed to the relevant HPV types. The efficacy of Gardasil, which includes results from an HPV-16 prototype of Gardasil, was evaluated in four placebo-controlled, double-blind, randomized Phase II and Phase III clinical studies. Together, the Phase II and III studies evaluated 20,541 women aged 16 to 26 years. Study participants were followed for up to five years after enrolment.

The studies' primary analyses were conducted in women who received all three vaccinations within one year of enrollment, did not have major deviations from the study protocol and were naïve to the relevant HPV type(s) prior to dose one and through one month post-dose three (Month 7). Efficacy was studied in the individual studies and in combined analyses and measured starting after the Month 7 visit. In the combined analyses Gardasil prevented 100 percent of HPV 16- and 18- related cervical pre-cancers and non-invasive cervical cancers (CIN 2/3, and AIS, or adenocarcinoma in situ). There were no cases in the 8,487 women who received Gardasil compared to 53 cases in the 8,460 women who received placebo. It also prevented 95 percent of low-grade cervical dysplasia (low grade lesions) and pre-cancers (CIN 2/3 or AIS) caused by HPV 6, 11, 16 or 18. There were 4 cases in the 7,858 women who received Gardasil compared to 83 cases in the 7,861 women who received placebo. It prevented 99 percent of cases of genital warts caused by HPV 6 or 11. There was one case in the 7,897 women who received Gardasil compared to 91 cases in the 7,899 women who received placebo.

Gardasil also prevented 100 percent of HPV 16- and 18-related vulvar and vaginal pre-cancers (VIN 2/3 or VaIN 2/3) in women not previously exposed to the relevant HPV types. There were no cases in the 8,641 women who received Gardasil compared to 24 cases in 8,667 women who received placebo. VIN 2/3 and VaIN 2/3 are the immediate precursors to vulvar and vaginal cancers.

These studies also showed that administration of Gardasil to women who are already infected with one or more vaccine related HPV types prior to vaccination protects them from clinical disease caused by the remaining vaccine types but may not alter the course of an infection that is already present.

In all studies, Gardasil was generally well tolerated and few subjects (0.1 percent) discontinued due to adverse events. Vaccine-related adverse experiences that were observed in clinical trials at a frequency of at least 1.0 percent among recipients of Gardasil and also greater than those observed among recipients of placebo, respectively, were pain (83.9 percent vs. 75.4 percent), swelling (25.4 percent vs. 15.8 percent), erythema (24.6 percent vs. 18.4 percent), fever (10.3 percent vs. 8.6 percent), and pruritis (3.1 percent vs. 2.8 percent). Most injection-site reactions were reported to be mild to moderate in intensity.

Prior vaccination strategies have shown that the ideal time to administer any vaccine is before exposure to the infection. Adolescents are an important group to vaccinate against HPV - one in four people ages 15 to 24 are infected with HPV. In addition, in a survey of 525 mothers with children as young as 11 years, up to 80 percent of mothers said they would allow their daughters to receive a vaccine that helps protect against cervical cancer.

Merck studied the anti-HPV 6, -11, -16 and -18 immune responses for Gardasil in 10-to 15-year-old girls compared to those in 16- to 23-year-old adolescent and young adult women. Among the study participants who received Gardasil, the immune responses (geometric mean titers, GMTs) in 10- to 15-year-old girls were similar to those in 16- to 23-year-old women. Similar outcomes were observed in a comparison of immune responses among 9- to 15-year-old girls to immune responses in 16- to 26-year-old adolescents and females. Based on these analyses, the FDA approved Gardasil for use in adolescent girls ages 9 to 15.

Studies examine impact of Gardasil in the general population
A secondary analysis to assess the potential impact of Gardasil on rates of cervical cancer and other HPV-related diseases on the general population was also conducted. This analysis included all women regardless of whether they were infected with HPV prior to vaccination, developed an infection after the start of vaccination and those who may not have completed the 3-dose vaccination. In this analysis, Gardasil reduced the risk for development of cervical pre-cancerous lesions and cervical cancer caused by HPV types 16 and 18 by approximately 40 percent in just two to four years. Genital warts (related to type 6, 11, 16 and 18), which develop more quickly than cervical cancer and pre-cancerous lesions, were reduced by almost 70 percent. Virtually all of the cases of CIN and genital warts seen in subjects who received Gardasil resulted from infections that were present when the women received their vaccination.

In the United States, approximately 20 million people are infected with HPV, and approximately 80 percent of females will have acquired HPV by age 50. For most people, HPV goes away on its own; however in some, certain high-risk types of HPV, if unrecognized and untreated, can lead to cervical cancer. In the United States, approximately 10,000 women are diagnosed with cervical cancer every year, and an average of 10 women die each day from the disease. Cervical cancer is the second most common cause of cancer death in women worldwide, resulting in nearly a half-million diagnoses and 240,000 deaths each year. In addition, certain low-risk types of HPV cause genital warts and can lead to abnormal Pap results. Approximately 1 million cases of genital warts occur each year in the United States and an estimated 32 million cases occur worldwide. Additionally, there are an estimated 4.7 million abnormal Pap results that require follow-up each year in the United States. At least 3 million of these results are caused by some type of HPV. HPV related disease, including screening, follow-up and treatment, costs about $5 billion per year in the U.S. Used in conjunction with screening, Gardasil can help significantly reduce the human and economic burden of cervical cancer and other HPV-related diseases in the United States.

In 1995, Merck entered into a license agreement and collaboration with CSL Limited relating to technology used in Gardasil. Gardasil is the third new Merck vaccine to be approved by the FDA in 2006. ROTATEQ® received FDA approval in February to prevent rotavirus gastroenteritis, a leading cause of severe infant diarrhea, and ZOSTAVAX® was approved by the FDA and in the European Union in May to prevent shingles in adults 60 and older. Other regulatory agencies around the world are reviewing applications for Gardasil, ROTATEQ and ZOSTAVAX.

On June 1, 2006, Gardasil was approved in Mexico. Applications for Gardasil are currently under review with regulatory agencies on five continents, including but not limited to agencies in Argentina, Australia, Brazil, the European Union, New Zealand, Singapore and Taiwan. Additionally, Merck is actively working to accelerate the availability of Gardasil in the developing world: in December, Merck announced a partnership with India's Council of Medical Research to study Gardasil. Merck is also working with PATH and the Gates Foundation to develop HPV vaccination programs that will facilitate introduction of Gardasil to the most impoverished nations.

HPV Vaccination: Predicting Its Effect on Cervical Cancer Rates

Wed, 05 Apr 2006 21:20:37 PST

( from http://www.rxpgnews.com ) Each year, nearly 500,000 new cases of cervical cancer are diagnosed around the world, and more than 250,000 women die from the disease. Most of these cases occur in developing countries where there is no routine screening for precancerous lesions. By contrast, in developed countries, national screening programs have greatly reduced the number of women dying from this cancerbetween 1955 and 1992 in the US, for example, cervical cancer deaths dropped by 74%.

Infection with a sexually transmitted human papillomavirus (HPV) is a precondition for the development of cervical cancer. Of the 35 HPV types that can infect the genital tract, about half have oncogenic potentialthe rest cause benign warts. The immune system clears most HPV infections but persistent infection with HPV type 16 accounts for approximately 55% of cervical cancers. Because of the strong association between cervical cancer and HPV infection, several HPV type-specific vaccines are being developed. Early results suggest that these vaccines can prevent almost 100% of persistent infections with the relevant HPV type, raising the possibility of reducing the incidence of cervical cancer by prophylactic vaccination. But what would the impact of such vaccines be in countries that already have cervical cancer screening programs? To find out, Ruanne Barnabas and colleagues have developed a dynamic transmission model of HPV 16 infection and progression to cervical cancer using epidemiological data from Finland. Their analyses indicate that high coverage of women alone over many decades with a vaccine that provides long-term protection would greatly reduce type-specific cancer incidence, a reduction that would be maximized by combining vaccination with routine screening.

The researchers' model is represented by a flow chart in which susceptible women acquire an HPV infection that, in most cases, is cleared by their immune system. In some women, persistent infection induces precancerous lesions that can progress to invasive cervical cancer, regress spontaneously, or be screened and treated. HPV infection in men is represented by a simpler flow chartthey simply become infected and then develop immunity. The researchers incorporated values for parameters such as sexual activity, screening protocols, and treatment rates obtained from published Finnish studies in their model and calibrated it using historical data on the proportion of the Finnish population with antibodies to HPV 16.

To allow them to model how vaccination will affect the incidence of cervical cancer, Barnabas and colleagues first estimated the transmission probability of HPV in the Finnish population. This probability provides a measure of how easily HPV spreadsif it were 1.0, every sexual partnership a woman had with a man infected with HPV would result in her also becoming infected. The researchers' transmission probability estimate of 0.6 is high, which indicates that universal coverage with a very effective vaccine will be needed to eliminate HPV infection in the population. The researchers put this value (which is subject to great uncertainty) and estimated values for age at sexual debut and the annual number of sexual partners into their model; they also assumed that vaccination takes place before sexual debut, is 100% effective, and gives life-long protection.

The model predicts that vaccinating both men and women will be little better than vaccinating women alone, irrespective of whether vaccine coverage is high or low. Furthermore, although vaccinating 90% of young women before sexual debut could decrease HPV type-specific cervical cancer incidence by 91%, delaying vaccination until after sexual debut could decrease the impact of vaccination. The model also predicts that if 90% of women were vaccinated without screening, there would be 0.6 cases of cervical cancer per 100,000 women per year (compared with seven out of 100,000 with no intervention); vaccination plus screening every five years would reduce this incidence further, by two-thirds. Finally, the researchers investigated how the duration of vaccine-conferred protection might affect invasive cervical cancer rates. The model predicts thatunintuitivelyshort-lived protection will marginally increase cervical cancer rates compared with no vaccination if, as some people believe, older women are more susceptible to the persistent HPV infections that progress to cervical cancer than are younger women. Booster vaccinations would avoid this potential problem.

The researchers conclude that the most effective strategy for the reduction of cervical cancer in developed countries in which incidence is already low is widespread vaccine coverage (both in terms of the HPV type targeted and the fraction of the population vaccinated), combined with current screening protocols. Whether this recommendation is adopted will depend on how vaccines perform in ongoing phase III trials and on a detailed economic assessment of the options available.

HPV testing is more sensitive for screening cervical cancer

Mon, 03 Apr 2006 14:31:37 PST

( from http://www.rxpgnews.com ) The current technique for screening for cervical cancer involves collecting cells by way of a pap smear and examining them under a microscope. Although this method has reduced cervical cancer in countries where it is regularly used, it has several weaknesses. A new study found that the test for human papillomavirus (HPV), which is present in almost all cervical cancers, is more sensitive than cytology (cell examination) in detecting cervical cancer.

Cytology is currently the gold standard for cervical cancer detection, but it has several limitations: high-quality samples must be collected; identifying the cell changes that may lead to cancer is highly subjective; and the method itself is very repetitive, which can further lead to interpretive errors. Several studies have shown that HPV testing is more sensitive than cytology at detecting cervical intraepithelial neoplasia (CIN), the changes in cervical cells that can lead to cancer. The current study was an analysis of data from several countries comparing the two methods.

Led by Jack Cuzick, Ph.D., of the Cancer Research UK Department of Epidemiology, Mathematics and Statistics at Queen Mary School of Medicine in London, researchers performed an overview on patient data for more than 60,000 women in the United Kingdom, France, Germany, the Netherlands, the United States and Canada. They analyzed the comparison of HPV testing to cytology both overall and for different age groups. The results showed that HPV testing was very sensitive (96 percent overall) in all the studies and that this sensitivity was not affected by age of patient. Cytology was substantially less sensitive than HPV testing (53 percent overall, although results varied widely) but it was more effective in women over 50 than in younger women. HPV testing was less specific for women under 35, but for older women the differences in specificity between the two methods were quite small. Specificity refers to the percentage of people who are disease-free and who test negative. There will always be some people who do not have the disease, but who are positive for the screening test (HPV or cytology).

"While well-conducted screening programmes based on cytology have undoubtedly led to a large reduction of cervical cancer in some countries, the high variability in sensitivity reported here indicates the need for strict quality control," the authors note. "HPV testing is highly reproducible, more easily monitored, provides an objective test outcome and can easily be automated." Since only persistent HPV infections are thought to be associated with pre-cancerous lesions, they suggest that procedures need to be developed for repeat testing to detect infections that may be transient, especially in younger women. They also suggest performing the HPV test as the sole primary test, since it is the more sensitive of the two methods, and follow it with cytology, the more specific test, in those who test positive initially.

A recent statement from the International Agency for Research on Cancer (IARC) concluded that HPV testing could reduce the incidence and mortality from cervical cancer and that it is likely to be at least as effective as cytology. The English Cervical Screening Advisory Committee has recently accepted the IARC statement and agreed that the HPV test could be used by the national screening program. "These statements should be influential in establishing streamlined large-scale demonstration projects employing HPV testing as part of primary screening," the authors conclude. "Such projects are needed to determine how best to implement this new test, and to see if it can reduce invasive cancer rates below those now achieved with cytology-based programmes."

Community's income status predicts cervical screening rates

Tue, 27 Dec 2005 17:16:38 PST

( from http://www.rxpgnews.com ) African-American women living in communities with high poverty rates are less likely to be screened for cervical cancer, even after adjusting for other factors known to raise the risk of non-screening, such as older age, lower educational attainment, and smoking.

The study, appearing in the February 1, 2006 issue of CANCER (http://www.interscience.wiley.com/cancer-newsroom), a peer-reviewed journal of the American Cancer Society, demonstrates that a community's income status predicts cervical screening rates.

Screening for cervical cancer using the Pap test has long been shown to be a cost-effective screening tool to reduce mortality. Mortality rates from cervical cancer have dropped 50 to 70 percent since the test's introduction. However, disparities in screening rates persist among different ethnicities, often blamed on individual factors, such as lack of access to regular healthcare, older age, obesity, and health status. A few studies now show that community and state level factors contribute to low screening rates among black women. However, those studies have thus far failed to distinguish the impact between these and other factors.

Led by Geetanjali Dabral Datta, Sc.D., M.P.H. of the Harvard School of Public Health in Boston, researchers investigated the relationship between individual characteristics and larger socioeconomic factors and their impact on recent cervical cancer screening rates. To do this they analyzed responses from over 40,000 African American women across the United States who participated in the Black Women's Health Study of Boston University and Howard University.

The investigators found that after adjusting for individual factors, residing in a community where at least 20 percent of the population lives below the poverty line was a significant predictor of failure to receive cervical cancer screening using the Pap test. State of residence was also found to be a predictor, but this association was not explained by the level of poverty in the state.

"The study adds to the literature by demonstrating that [community] and state factors influence cervical cancer screening behaviors above and beyond individual factors," the authors conclude. Further, they recommend "that community outreach programs should focus on high poverty neighborhoods to decrease the proportion of black women who are not adhering to cervical cancer screening recommendations."

Novel technique to remove "inoperable" cervical spinal tumours

Sun, 06 Nov 2005 11:22:38 PST

( from http://www.rxpgnews.com ) UCSF surgeons are using a novel technique to remove tumors from the cervical region of the spine that were previously thought "inoperable."

Called a lateral paramedian transpedicular approach, the technique uses advances in spinal instrumentation and reconstructive strategies to provide a direct approach to the removal of cervical spinal tumors with minimal, or no, neural manipulation.

The procedure is reported in the November issue of Operative Neurosurgery. UCSF is the only medical institution in the United States where patients can undergo this surgery.

Developed by neurosurgeon Christopher Ames, MD, co-director of neurospinal disorders and director of the Spinal Biomechanics and Spinal Neuronavigation Laboratory at UCSF Medical Center, the surgery uses standard and innovative devices to first remove and then reconstruct portions of the cervical spine in order to access tumors. Once the bone is removed, surgeons have a direct line of sight to the tumor and are able to remove it in its entirety without having to move or manipulate the spinal cord.

After the tumor is removed, surgeons immediately rebuild the spine with artificial pedicle screws, a reconstruction technique also developed by Ames. The technique is particularly useful in cases in which the tumor is located in the middle of the spinal canal and attached to the lining of the spine. These types of tumors include meningiomas, neurofibromas and exophytic astrocytomas.

Patient Stacey Hall recently underwent surgery to remove a neurofibroma, a usually benign tumor of the peripheral nerves. Hall's tumor caused her skin to be acutely sensitive to touch, her hands to experience numbness, and her legs to collapse from under her at times. "The damage was so severe, the slightest breeze against my skin caused me excruciating pain," said Hall. "The first thing I noticed after my surgery was that my skin no longer hurt for the first time in more than a year."

Most of the surgeries to date have been done on patients with conditions similar to Hall. Neurofibromas can occur as a sporadic condition or as a genetic disorder such as neurofibromatosis. While a common type of spinal tumor, neurofibromas are challenging lesions to approach surgically, according to Ames. Found at the base of the skull on or near the spine, the tumors often sit just below the brain stem and press against the spinal cord as they grow.

Some tumors span several vertebral levels. In time, the pressure against the spinal cord can cause pain, numbness and loss of mobility in the hands, arms and legs. If left untreated, patients can become paralyzed. Because of the proximity to sensitive anatomy including the spinal cord, pharynx, nerves, and major blood vessels, surgeons often refuse to operate for fear of causing irreversible nerve damage, paralysis and even death, Ames noted, and as a result, patients presenting with extensive intradural tumors are often left without hope.

"We are treating patients with this technique who were told by physicians that nothing more could be done," said Ames. "The next step is to train other surgeons in the technique so it is accessible to patients throughout the country."

HPV Vaccine Prevented 100 Percent of Cervical Pre-cancers

Fri, 07 Oct 2005 13:54:38 PST

( from http://www.rxpgnews.com ) A quadrivalent human papillomavirus types 6, 11, 16, 18, recombinant vaccine (GARDASILTM), an investigational vaccine from Merck & Co., Inc., prevented 100 percent of high-grade cervical pre-cancers and non-invasive cervical cancers (CIN 2/3 and AIS) associated with human papillomavirus (HPV) types 16 and 18 in a new phase III study. The analysis compared GARDASIL to placebo in women who were not infected with HPV 16 and 18 at enrollment and who remained free of infection through the completion of the vaccination regimen. Women were followed for an average of two years after enrollment.

This trial is part of the ongoing phase III program for GARDASIL, which involves over 25,000 people in 33 countries worldwide. Merck remains on track to submit a Biologics License Application for GARDASIL to the Food and Drug Administration in the fourth quarter of 2005.

More than 12,000 women from 13 countries participated in this trial
This phase III study, titled FUTURE II, is a prospective, randomized, double-blind, placebo-controlled study with two vaccination groups. Women aged 16 to 26 years were randomized to receive a three-dose regimen of either GARDASIL or placebo at Day 1, Month 2, and Month 6. A total of 12,167 women were enrolled from 90 study centers in Brazil, Colombia, Denmark, Finland, Iceland, Mexico, Norway, Peru, Poland, Singapore, Sweden, the United Kingdom and the United States (including Puerto Rico) and were equally allocated between the two groups. A group of 6,082 females received GARDASIL and another group of 6,075 received placebo.

FUTURE II evaluated the incidence of HPV 16/18-related cervical pre-cancers known as CIN (cervical intraepithelial neoplasia) 2/3 and non-invasive cancers. CIN 2 is a moderate-grade lesion of the cervix. CIN 3 represents both high-grade lesions and CIS (carcinoma in situ), the immediate pre-cursor to invasive squamous cell cervical cancer. AIS (adenocarcinoma in situ) is the early development of adenocarcinoma (or glandular cancer) of the cervix. CIN 3 and AIS are defined as Stage 0 cancer according to the International Federation of Gynecology and Obstetrics (FIGO) classification.

The primary analysis of this trial evaluated the incidence of CIN 2/3 and AIS in women who received three doses of GARDASIL, had no major protocol violations and remained free of HPV 16 and/or HPV 18 infection through month 7; this analysis started 30 days after completion of the vaccination regimen, and followed women for an average of 17 months after completion of the regimen. In this group, GARDASIL prevented 100 percent of cases of high-grade pre-cancer and non-invasive cancer (CIN 2/3 or AIS) associated with HPV types 16 and 18 (p < 0.001); no cases of CIN 2/3 or AIS were observed in the vaccine group (n=5,301) compared to 21 cases in the placebo group (n= 5,258).

"These are the first pivotal data to show that vaccination with GARDASIL reduced HPV 16 and18-related cervical pre-cancer and non-invasive cervical cancer," said Laura Koutsky, Ph.D., principal investigator, HPV research group, University of Washington, Seattle.

A secondary analysis, also being presented, evaluated the incidence of CIN 2/3 and AIS in a broader group of women. This analysis started 30 days after administration of the first dose of GARDASIL or placebo, and included all of the women in the primary analysis group, as well as women who may have become infected with HPV 16 or HPV 18 during the vaccination period and women who may have violated the protocol in significant ways (for example, by missing certain protocol visits). On average, these women were followed for approximately two years. In this group, GARDASIL reduced the risk of developing high-grade pre-cancer and non-invasive cancer (CIN 2/CIN 3, or AIS) associated with HPV types 16 and 18 by 97 percent (n= 5,736); one case was observed in the vaccine group compared to 36 in the placebo group (n= 5,766).

There were no discontinuations due to serious vaccine-related adverse events. Adverse events were higher among those who received GARDASIL compared with placebo recipients. The most common vaccine-related adverse event reported was local discomfort at the injection site.

"Merck has been committed to vaccine research and development for over a century," said Peter S. Kim, Ph.D., president, Merck Research Laboratories. "We have hope that GARDASIL will continue the great Merck tradition of developing medicines and vaccines that make a real difference in people's lives."

GARDASIL was designed to target HPV types 16 and 18, which account for 70 percent of cervical cancers, and HPV types 6 and 11, which account for 90 percent of cases of genital warts. These four types also cause benign cervical changes that result in "abnormal" Pap tests.

GARDASIL is one of three late-stage vaccines in development at Merck. In April, Merck submitted Biologics License Applications to the FDA for ROTATEQ, a vaccine for rotavirus gastroenteritis, and ZOSTAVAX, a vaccine for shingles.

Approximately 20 million American men and women are infected with HPV
HPV has been identified as the cause of cervical cancer, pre-cancers, benign cervical lesions and genital warts. Cervical cancer, one of the leading cancers among women, results in approximately 290,000 deaths worldwide each year. In the United States an estimated 10,400 new cases of cervical cancer will be diagnosed in 2005, and there will be an estimated 3,700 deaths from cervical cancer. It is estimated that approximately 20 million men and women in the United States are infected with HPV. In most people, HPV goes away on its own. In some, however, certain high-risk or oncogenic types of HPV can lead to cervical cancer. The virus is also associated with abnormal Pap tests and genital warts. Each year, about one million women in the United States are told they have "an abnormal Pap" - which may trigger additional testing, anxiety, and in some cases fears of cancer.

In 1995, Merck entered into a license agreement and collaboration with CSL Limited relating to technology used in GARDASIL. GARDASIL is also the subject of other third-party licensing agreements.

Clues to 'disappearing' precancers uncovered

Fri, 01 Jul 2005 12:56:38 PST

( from http://www.rxpgnews.com ) New research sheds light on why cervical precancers disappear in some women and not in others. Scientists at the Johns Hopkins Kimmel Cancer Center report in the July 1 issue of Clinical Cancer Research that the reason many of these lesions persist is an unlikely mix of human papilloma virus (HPV) strain and a woman's individual immune system.

For decades, scientists have known that HPV causes nearly all cases of cancer in the neck of the womb. Most sexually active women some reports say up to 80 percent are exposed to HPV and more than half of these women are infected with strains of the virus that could likely turn a precancerous lesion to cancer. But only a small percentage of precancers progress to full-blown cancer, a process that takes years.

To find out why, gynecologic oncologist Cornelia Trimble, M.D., closely monitored 100 women with high-grade, precancerous cervical lesions before standard surgery to remove the abnormal tissue. Some of the lesions about 28 percent -- regressed by themselves before surgery within a time period considered within the bounds of care standards. But among patients whose pre-cancers lingered, Trimble discovered that women were three times less likely to resolve their lesions if they carried a certain immune system gene and did not have HPV16, the most common strain of the virus.

Trimble was particularly interested in these molecular differences because she is using HPV-targeted vaccines in related studies to treat early cervical lesions before they turn into cancer. "It's important for us to know the immunologic fingerprint of women who may best benefit from our vaccine," she says. "Some lesions are on the brink of resolving, but may need the vaccine to push them over."

Lesions containing HPV16 alone are the most troublesome and difficult to resolve. In the subset of 44 patients with HPV16 only, their type of immune system made no impact on whether or not their lesion resolved. But in 30 women with non-HPV16 lesions, those who carry a gene called HLA*A201 were three times less likely to clear up their lesions than those without the gene (14.3 percent vs. 42.3 percent). According to Trimble, 40 percent of people carry the HLA*A201 gene, which codes for certain white blood cell proteins.

None of the lesions got worse during the study period, and all unresolved lesions were surgically removed when the observation period ended. "Since none of the lesions progressed after 15 weeks, we can be reasonably assured that this window of time is safe for vaccine treatments," she said.

Trimble is studying a larger group of patients to confirm her results and rule out other potentially confounding factors such as age, smoking status, and contraceptive method, which may influence how these lesions clear. Trimble recently published results linking second-hand cigarette smoke to cervical cancer progression. She also is looking for additional immune system characteristics that could predict mechanisms of immune responses to HPV. This may provide more information on which women have lesions more likely to regress and potentially avoid surgery, plus provide the opportunity to treat early-stage disease.

Failure to Screen, Pap Test Failure Most Common Reasons for Cervical Cancer Diagnosis

Wed, 04 May 2005 17:25:38 PST

( from http://www.rxpgnews.com ) Increasing Pap screening adherence and improving the accuracy of Pap screening could reduce the incidence of invasive cervical cancer among women with access to screening and could afford earlier detection of cervical cancer, a new study concludes.

Cervical cancer is highly preventable and treatable. Therefore, the occurrence of an invasive cervical cancer represents a failure in the screening process. To elucidate factors associated with screening failure, Wendy A. Leyden, of Kaiser Permanente in Oakland, Calif., and colleagues examined the medical records of 833 women enrolled in one of seven comprehensive health care plans who were diagnosed with cervical cancer despite having access to cancer screening and treatment services.

They found that 56% of cases were in women who had not had a Pap test during the period 4 to 36 months prior to diagnosis, whereas 32% of cases were attributed to Pap test detection failure and 13% of cases to failure to follow up an abnormal test result. Most (81%) of the women with no Pap screening had had at least one unrelated outpatient visit 4 to 36 months prior to their cancer diagnosis.

"Despite the many exciting new technologies that may improve our ability to predict or detect cervical neoplasia, we must not lose sight of the need to increase screening adherence," the authors write. "Even the most perfect screening method will not detect disease in a woman who has not participated in the prevention process."