Cervical Cancer Vaccines May Start Soon
A cervical cancer vaccine programme is likely to be introduced in the Republic in the near future, on foot of today’s publication of a Health Information and Quality Authority (Hiqa) report.
The HIQA value-for-money report should pave the way for the early announcement of a formal immunisation programme aimed at 12-year-old girls. The report also recommends a once-off vaccination programme for 13 to 15 year-olds.
Cervical cancer is caused by certain types of the human papillomavirus (HPV), with evidence of infection found in 99 per cent of women with cervical cancer.
The Minister for Health, Mary Harney has said she would introduce a HPV/cervical cancer vaccine programme if advised to do so.
Although there are in excess of 200 HPV strains, just a small number are associated with the development of cancer of the cervix. HPV types 16 and 18 are found in almost 70 per cent of cervical cancers, while another five sub types are responsible of a further 20 per cent of cases. Some HPV types are non cancerous but are linked to the presence of warts in the genital area.
Cancer of the neck of the womb (cervix) is diagnosed in almost 200 women here every year; some 70 women die from the disease annually.
Cervical cancer usually develops quite slowly, passing through a number of pre invasive stages (carcinoma in situ - CIN) before progressing to full blown disease. If caught in the early stages, it has a five-year survival rate of 80 per cent or greater.
HPV is a sexually transmitted infection; it is estimated that almost 80 per cent of sexually active people have been infected with at least one virus type by the age of 50. It is usually symptomless and in 90 per cent of cases, the body clears itself of the virus within two years of infection. But it is when the virus persists that the risk of cervical cancer increases.
Gardasil and Cervarix are the approved vaccines against HPV. Both aim to prevent cervical cancer; in addition Gardasil is active against those HPV subtypes known to cause genital warts. Both products involve a three-vaccine course, given over a six-month period. And clinical trials involving a five-year follow-up, have shown that vaccination is 100 per cent effective in preventing HPV infection and non-invasive cancer .
HPV vaccines must be given before infection with the virus occurs. This means administering the course prior to the person becoming sexually active so that a comprehensive vaccination program would need to be administered to girls in the 11- to 13-year age bracket.
Vaccination Against Human Papillomavirus Decreases Related Tests and Treatment for Cervical Cancer
Researchers affiliated with the Quadrivalent HPV Vaccine Merck Study Group have reported that vaccination against human papillomavirus (HPV) is associated with a reduction in Pap tests, colposcopy, cervical biopsy, and definitive treatment among women who were uninfected at the time of vaccination. The details of this study were presented at the 39th annual meeting of the Society of Gynecologic Oncologists (SGO) in Tampa, Florida, from March 9 to 12, 2008.
Pap smears have decreased the incidence and death rate of cervical cancer among women in developed countries such as the United States. Cervical cancer is caused by specific high-risk strains of HPV, which can be detected by a special test called Hybrid Capture II (made by Digene).
Now that an HPV vaccine (Gardasil®, manufactured by Merck) has been approved by the U.S. FDA, further reductions in cervical cancer incidence and death may be anticipated. Gardasil is a quadrivalent vaccine because it confers protection against four subtypes of HPV (HPV 6 and HPV 11, which cause 90 percent of genital warts, and HPV 16 and HPV 18, which cause 70 percent of cervical cancers).
Despite the success of Pap smear programs and the ability to detect HPV, over 2 billion dollars in healthcare expenditure occurs annually as a result of abnormal Pap tests and their subsequent evaluation, which often requires cervical biopsies and other surgical procedures on the cervix. This is because, although Pap smears and HPV detection allow a pre-cancerous or dysplastic state of the cervix to be detected and treated before it can turn into cancer, neither of these two methods eliminate the original problem, which is infection with HPV.
The end-of-study data from three pivotal Phase II/III clinical trials of the quadrivalent HPV vaccine were reported at the SGO meeting. A total of 18,150 16 to 26-year-old women were enrolled in one of three randomized, placebo-controlled trials. Vaccine or placebo was given at Day 1, Month 2, and Month 6. Subjects underwent Pap testing on Day 1 and every six to 12 months for up to 48 months. Patients with specific abnormalities on the Pap smear were referred for colposcopy and, depending on the findings, definitive treatment was carried out.
After an average follow-up period of four years, the investigators noted a reduction in Pap tests, colposcopy, cervical biopsy, and definitive treatment among women who were uninfected with HPV at the time of vaccination. Interestingly, these reductions were seen irrespective of the specific type of HPV involved.
Comments: Vaccination with the quadrivalent vaccine appears to be able to decrease the number of Pap tests, colposcopies, cervical biopsies, and treatment women require. This occurs presumably because the vaccine protects against infection with HPV, which is the inciting event in the development of pre-cancerous cervical disease. Long-term studies are required to determine the duration of protection that is achieved by the three-dose vaccination series.
Gen-Probe HPV assay launched in Europe
Gen-Probe has launched its new Aptima HPV Assay in Europe. The diagnostic test, for detecting high-risk strains of the human papillomavirus (HPV), has been CE-marked and is now available for sale in 13 European countries.
The assay is an amplified nucleic acid test that detects 14 high-risk HPV types associated with cervical cancer. Specifically, it detects two messenger RNAs (mRNAs), E6 and E7, that are made in higher amounts when HPV infections progress toward cervical cancer. Gen-Probe believes that targeting these mRNAs may more accurately identify women at higher risk of having, or developing, cervical cancer than competing assays that target HPV DNA. Detecting HPV DNA identifies women who are infected, but HPV infections are common and many resolve without causing cervical cancer.
“Increased specificity – meaning fewer false positive results – is important so women are not subjected to the anxiety and expense of unnecessary medical procedures,” said Jack Cuzick, professor of epidemiology at the Cancer Research UK Centre for Epidemiology, Mathematics and Statistics in London, who is leading the 953-woman ‘Predictors’ study – a head-to-head comparison of various HPV assays.
The assay has been designed to run on Gen-Probe’s fully-automated Tigris instrument system and on the company’s semi-automated DTS instrument platform.
It is being manufactured in Cardiff by Molecular Light Technology, a subsidiary of Gen-Probe.
The assay is still in clinical studies in the US, and has not yet been approved for marketing in that country by the US Food and Drug Administration.
HPV is a group of viruses with more than 100 types, 14 of which are considered to be high-risk for the development of cervical cancer. Most women will be infected with HPV at some point in their lives, but most of these infections resolve without any clinical symptoms or consequences. A small number of HPV infections progress and result in disease, which can range from genital warts to cervical cancer.
HPV Vaccine & Fainting
by Amy Fleming
Allentown, PA - Recently the Centers for Disease Control & Prevention reported that in the last two years, more than 450 youngsters fainted after getting a vaccination.
That may explain why some teenagers are taking a new position on the HPV vaccine.
Gardasil protects against a virus that cervical cancer and genital warts.
Researchers aren’t sure why, but about 10% of girls in studies for the HPV vaccine got dizzy or passed out after the shot.
The Gardasil website lists fainting as a possible side effect.
To be safe rather than sorry, doctors are proposing an easy solution.
“The recommendation as a result of this, is pretty simple. Just that you give them a vaccine either sitting sown or lying down and you watch them for 15 to 20 minutes just to make sure that they don’t have any significant reaction,” said Dr. Larry Glazerman.
The vaccine is given in a series of three shots.
For more information on the vaccine go to www.gardasil.com.
More links found between cancer in men and HPV, but men aren’t approved for vaccination
by Brian Boyer
Men are neither vaccinated nor screened for human papillomavirus, but two university studies suggested last week that it may be the cause of cancer for many men, and that those cancers could have been prevented.
The virus, better known as HPV, is the primary cause of cervical cancer in women. Recent research, at the University of Michigan and University of Louisville, suggests that it is also the cause of a disease that disproportionately affects men, cancers of the head and neck.
“You should be testing everybody,” said Payal Desai, leader of a pilot study at the Louisville’s James Graham Brown Cancer Center. Both men and women carry HPV, the virus that will affect at least 50 percent of sexually active people, according to the Food and Drug Administration, though only a fraction of those will develop cancer.
More than 35,000 new cases of head and neck cancer are expected to be diagnosed in the United States in 2008, according to the American Cancer Society. Twice as many men as women will develop the disease, which the society estimates will kill 7,590 Americans this year.
Currently a screening test only exists for women. Similarly, a vaccine for HPV exists, but is only approved for use in women ages 9 to 26. Studies are under way to test the efficacy of the HPV vaccine in men, according to the FDA.
If the vaccine were successful in preventing HPV infections in men, the studies suggest it is possible that a significant number of cancer cases in men could be avoided.
In one study, tissue samples from 43 head and neck cancer patients were tested by the Louisville team. They found that almost one-third of the samples tested positive for HPV, specifically the strain of the virus known as HPV 16.
In the other study, at Michigan’s Comprehensive Cancer Center, had similar findings. More than one-third of the 66 head and neck cancer cases they examined tested positive for HPV 16. This study’s primary finding was encouraging: The HPV-associated tumors responded significantly better to treatment than those not associated with HPV.
In women, HPV types 16 and 18 are responsible for 70 percent of cervical cancer cases. The American Cancer Society estimates that 11,070 cases will be diagnosed, and that the disease will kill 3,870 women in the United States in 2008.
Infection by strains 16 and 18 can be prevented through vaccination, with almost 100 percent effectiveness. The drug Gardasil, first made available to young women in 2006, also vaccinates against types 6 and 11, which are responsible for 90 percent genital warts cases.
Desai presented the findings of their study May 15 at the American College of Physicians Internal Medicine Conference. The results have not yet been published. The University of Michigan study was published online May 12 in the Journal of Clinical Oncology. In February, another study, at the National Cancer Institute and Johns Hopkins Medical Insitutions, suggested a link in men between HPV and oral cancer.
Boys should also get HPV protection
Kelly Sinoski, Vancouver Sun
Published: Saturday, May 17, 2008
B.C. I Boys as well as girls should be offered the free HPV vaccine to stop the spread of the cervical cancer-causing disease, former deputy health minister Dr. Penny Ballem says.
The vaccine, which will be offered by the provincial government to girls entering Grade 6 and 9 on a voluntary basis next year and women up to age 26, is not even licensed for use on males in Canada.
But Ballem insists that should change if the province is intent on controlling the spread of the human papillomavirus, which can lead to cervical cancer in women and genital warts and other cancers in both sexes.
“If you really want to wipe out a scourge, you have to go after the people who carry the virus and pass it on,” Ballem said. “There needs to be more of a burden on men in our society in protecting women.”
The virus is among the most common sexually transmitted infections in Canada. The vaccine, Gardisil, targets the two strains of the infection responsible for 70 per cent of cervical cancer.
Boys and men can only access the vaccine “off label” from their doctors if they want it but will have to pay the full cost, which is about $300 to $400 for treatment, said provincial health officer Dr. Perry Kendall.
Kendall said although there are calls to offer the vaccine to men, he doubts doctors are recommending it to males because of the high cost. Nor does he think it will be offered to the male population in the next year because it hasn’t been tested or licenced for use on males in Canada.
If it was to spend $100 million, he said, the government would likely to find other areas where the money could be better spent.
He noted it would about $8 million to vaccinate the Grade 6 girls, but said if you calculated over a lifetime how many deaths the vaccine would prevent and the quality of life for survivors, it works out to “$25,000 per quality of life adjusted year.”
For males, it would be about $35,000.
“The question is the return worth the investment?” he said.
“If the price comes down substantially it might be something you offered to both sexes.”
Kendall noted that while HPV can cause genital warts and a few hundred cases of penile and other cancers in males, it carries a higher risk for women, who can get cervical cancer and be possibly rendered sterile if they require invasive surgery to their cervix.
Cervical cancer is the second most common cancer for Canadian women aged 20 to 44, with 150 women contracting the disease each year, he said. Of those about 50 die annually.
“Far fewer boys die from cancer associated with HPV and no one dies from genital warts,” Kendall said. “We’re doing it for cancer.”
But Ballem said she doesn’t believe the decision to offer the vaccine to only girls and women was well thought out, noting there are “gaps in the coverage.”
The vaccination, which requires three shots over six months, will not prevent all cervical cancers, meaning women will still have to have annual pap smears, she said.
She added girls may even get false sense of security that sex is safer than it is because they’ve had the vaccine.
Apart from passing on the disease, she maintains that by vaccinating boys it would help boost immunity across the sexually active population.
She added women are more vulnerable to disease because they have more mucus membranes exposed to bodily fluids than men.
“The focus was never on where do they get the virus from? They get it from men,” Ballem said. “Frankly, maybe we should go after the source of HPV and the people who are spreading it around.”
Treating and Preventing HPV
Consequences of HPV
Understanding HPV
More throat, mouth cancers linked to HPV
By Jill Coley
Many young nonsmokers get disease as result of contracting virus from oral sexual contact
About once a week, Dr. Boyd Gillespie shocks a young nonsmoker with the diagnosis that he has cancer in the back of his mouth.
Most oral cancers are related to a lifetime of tobacco or alcohol abuse, but that profile is changing.
Gillespie, a head and neck cancer surgeon at the Medical University of South Carolina’s Hollings Cancer Center, is seeing an increasing number of patients who are young, have little if any smoking history and have cancers predominantly of the tonsil and the back of the tongue.
The culprit is human papillomavirus, or HPV, the same sexually transmitted virus that causes cervical cancer. The oral cancer does not discriminate between sexes, striking men and women at equal rates, Gillespie said.
About 25 percent of the 40,000 head and neck cancers annually in the United States, or about 10,000 cases, might be attributable to HPV, Gillespie said. A decade ago, the number of mouth cancers related to the virus was nearly zero.
It’s a trend that other head and neck practitioners around the country also have witnessed, he said. Boyd and virologist Natalie Sutkowski have studied and confirmed that factors such as age, smoking history and tumor location and appearance are highly predictive of which tumors are caused by HPV.
Risk factors are similar to those for cervical cancer: younger age of first sexual intercourse and multiple sexual partners. With throat and mouth cancers, oral sexual contact also is a factor.
“Oral sex is probably a bigger part of first sexual contact than maybe it was in the past,” Gillespie said. A 2005 national study reported that more than half of U.S. teenagers from 15 to 19 had engaged in oral sex. That percentage jumped to 70 percent by ages 18 and 19.
But the complete story of the virus’s transmission is not known. “It’s unclear if it’s only passed through sexual contact,” Sutkowski said. “It would not be impossible in my mind that it could be passed through kissing.” A recent study in Nature Clinical Practice Oncology reported that “direct mouth-to-mouth contact or other means could not be excluded.”
Another factor contributing to the rise in HPV-related oral cancers could be that doctors 10 years ago didn’t necessarily look for the virus, Sutkowski said, and methods of testing have improved.
Also, more people smoked 10 years ago, so it was easier to blame tobacco.
But as more patients in their 20s and 30s appeared who didn’t smoke or abuse alcohol, the medical community took note.
Symptoms of HPV-related oral cancer include a visible growth or lesion on the tonsils or the base of the tongue that might affect speech or swallowing.
The ulcer might be sore, might bleed and could cause hoarseness. Gillespie recommends patients seek medical attention if they’ve had symptoms for a month or longer.
Some positive news is that HPV-related oral cancers have a good prognosis. But early intervention is key, Gillespie said, as survival rates fall from 90 percent to 50 percent when the cancer spreads to the lymph nodes.
To help people get medical attention early, the Hollings Cancer Center will open the Oral Lesion Clinic this month. The clinic will be staffed by a head and neck surgeon and an oral pathologist who will evaluate sores, ulcers and growths in the mouth or throat. A majority of patients will be referred by doctors or dentists.
The increased attention could lead to a push in boys receiving the HPV vaccine, marketed as Gardasil by Merck.
There are more than 100 strains of HPV, about 13 of which are considered high-risk.
The vaccine protects against four types: HPV-16, which is responsible for half of cervical cancers and the majority of virus-related mouth and throat cancers, HPV-18, which is also responsible for cervical cancers, and strains 11 and 6, which are associated with genital warts.
Whether the vaccine protects against oral cancer remains to be seen but seems logical, Boyd said.
“Our hope is that by reducing the number of people incubating HPV-16 in the community, we will also see a dropoff of throat cancer.”
From virus to tumor
How a virus interacts with tissue and becomes a tumor is complicated. Virologist Natalie Sutkowski might have unlocked one process that contributes to human papillomavirus’s transformation to cancer.
Sutkowski has discovered an ancient viral conversation that takes place when HPV meets human DNA.
About 8 percent of human DNA is derived from virus particles that have worked their way into the human genome over millions of years, Sutkowski said.
Normally, these viral particles do nothing. But when HPV is introduced, the viral particles are activated and cause inflammation. The increased blood flow, in turn, nourishes tumors.
“It’s known that inflammation helps tumors grow,” Sutkowski said. “And these viral particles turn on inflammation. So maybe it’s just as simple as that — the inflammation may be helping tumors grow.”
Sutkowski, working closely with head and neck cancer surgeon Boyd Gillespie, is now turning her attention to searching for drugs to inhibit these ancient genes, stop the inflammation and interrupt the tumors’ growth.