HPV-16

HPV testing following excisional therapy for cervical neoplasia can identify high-risk patients: presented at IPC

Source: www.docguide.com
Author: Louise Gagnon

About one-quarter of women continue to have high-risk human papillomavirus (HPV) after excisional therapy for cervical intraepithelial neoplasia (CIN) 2/3, a study presented here at the 26th International Papillomavirus Conference (IPC) has found.

Women with CIN are at increased risk for developing invasive cervical cancer, and persistent infection of high-risk HPV is a main risk factor for treatment failure, said Wendy Mei, BSc, MLT, the study’s presenting investigator and clinical trials coordinator at the British Columbia Centre for Disease Control, Vancouver, British Columbia.

HPV testing and Pap smear together are more sensitive than using Pap smear alone, noted Mei.

“We wanted to evaluate the impact of implementing ASCCP [American Society for Colposcopy and Clinical Pathology] guidelines in British Columbia,” Mei told attendees here at an oral presentation on July 7. “We also wanted to determine the genotype distribution of women with higher risk HPV to gain insight on vaccine and diagnostics evaluation.”

Researchers used ThinPrep to collect cervical brushings, instead of conventional Pap smear, to permit an aliquot to be tested to determine if the HPV types were high-risk using a DNA test.

Mei and colleagues collected 1,007 specimens and found 25.4% (n = 256) were positive for high-risk HPV. They found HPV 16 in 29.7% of specimens and HPV 18 in 5.5% of specimens.

“HPV 18 was lower than expected, but the treatment options are more effective for HPV 18,” said Mei in an interview.

Investigators found single and multiple high-risk HPV genotypes were identified in 50.8% of specimens and 31.3% of specimens, respectively. As many as 9 genotypes were detected in 1 sample.

“Multiple infections were quite common, and there might be synergistic or competitive relationships where if you have a certain combination of genotypes, it might make the disease worse or prevent another genotype,” said Mei.

Detecting women who carry high-risk HPV genotypes can allow clinicians to streamline their energies to those women who are at greatest threat of developing cervical cancer, Mei explained.

“If we can identify those cases, we can focus our efforts on those at highest risk of developing cervical carcinoma,” said Dr. Mei, noting that women with high-risk HPV can be included in an intense screening program.

Both Digene and F. Hoffman-La Roche Ltd. supplied materials for investigators to conduct the study.

Note:
1. Presentation title: HPV Testing of Women in British Columbia Following Excisional Therapy for CIN 2/3. Abstract 414

Immune cells may guide therapy for oropharyngeal cancer

Source: www.medpagetoday.com
Author: Charles Bankhead, Staff Writer, MedPage Today

Higher pretreatment levels of cytotoxic T lymphocytes may help identify patients with head and neck cancer who have a favorable prognosis and require less aggressive treatment, according to a study reported here.

A higher proportion of CD8 cells predicted improved survival in patients with oropharyngeal cancer associated with human papillomavirus-16 (HPV-16), investigators reported at the American Head and Neck Society.

The finding supports the hypothesis that a patient’s adaptive immunity may play a role in the favorable prognosis of HPV 16-related head and neck cancer.

“We had hypothesized that a better immune status might be responsible for the better survival,” Gregory T. Wolf, MD, of the University of Michigan in Ann Arbor, said in an interview. “The next step will be find out what the function of these cells might be and whether they are really contributing to the control of the cancer or to good response to therapy.”

The results also support the feasibility of using a biologic marker to identify patients with head and neck cancer that can be treated less aggressively, sparing patients from some of the treatment-related morbidity, Wolf added.

Confirming the association between CD8 cells and survival is the latest step in a scientific journey that began about 15 years ago, when researchers and clinicians began to notice that a subgroup of patients with oropharyngeal cancer had a more favorable prognosis than would have been expected. Many of the patients tested positive for HPV, specifically HPV-16.

Wolf and colleagues previously found that pretreatment levels of CD8 and CD4 (helper T cells) were associated with a favorable prognosis in patients with head and neck squamous carcinoma. The current study was designed to define the association more specifically, particularly the contributions of a patient’s own adaptive immunity.

The study involved 66 patients with stage III-IV previously untreated head and neck cancer. Pretreatment peripheral blood lymphocyte subpopulations were assessed in 47 of the patients. Subset analysis included CD3, CD4, CD8, natural-killer, and B cells, as well as total white blood cell (WBC) count.

All patients received the same therapy: a single course of neoadjuvant chemotherapy, followed by either surgery or concurrent chemoradiation.

After a median follow-up of 6.6 years, four-year disease-specific survival was 76%.

Statistically significant predictors of improved survival were a higher percent CD8 level (P=0.043), lower expression of epidermal growth factor receptor (P=0.002), and HPV status (P=0.017).

HPV-positive patients had significantly higher levels of CD8 cells (P=0.038), a significantly lower CD4/CD8 ratio (P=0.021), and a lower total WBC (P=0.016).

A higher proportion of CD8 cells predicted an increased likelihood of response to induction chemotherapy (P=0.022) and complete tumor response after chemoradiation (P=0.045). Local failure was associated with low CD8 levels (P=0.035).

The mean WBC was higher and hemoglobin lower in smokers versus former smokers and nonsmokers, but lymphocyte subsets did not differ between smokers and nonsmokers.

The field of oropharyngeal cancer has changed dramatically in a relatively short period of time, said Wolf. As recently as the 1990s, about 25% to 30% of oropharyngeal cancers were HPV positive. Current estimates are in the range of 80% to 90%.

HPV-related oropharyngeal cancer affects men and women with roughly equal frequency. Most patients do not smoke, and most are not heavy drinkers, factors closely associated with other types of head and neck cancer.

As in HPV-associated cervical cancer, sexual activity is strongly associated with HPV-positive oropharyngeal cancer, Wolf continued.

Most specialists in oropharyngeal cancer now refer to the HPV-related cancer as a sexually transmitted disease, he said. Clinical trials are assessing whether vaccination against HPV can prevent the cancer in men as well as women.

“We’re in a paradigm-shifting kind of moment in head and neck cancer,” said Wolf. “Up to now, I think clinicians had been reluctant to accept a biologic marker, if you will, to help select treatment. The improved prognosis associated with HPV-16 is so consistent and so overwhelming that it will change the way clinicians approach these cancers.”

Notes:
1. Wolf disclosed a relationship with IRX Therapeutics.
2. Source: American Head and Neck Society
3. Reference: Wansom D, et al “Cellular immunity correlates with human papillomavirus-16 (HPV-16) status and outcome in patients with advanced oropharyhngeal cancer” AHNS 2010; Abstract S043.

Needed: HPV vaccine, simple screening test, for women and men

Source: jhu.edu/~gazette
Author: Valerie Mehl, Johns Hopkins Medicine

A call to explore a broader use of human papillomavirus vaccines and the validation of a simple oral screening test for HPV-caused oral cancers are reported in two studies by an investigator at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Leading HPV expert Maura Gillison, the first to identify HPV infection as the cause of certain oral cancers and who identified multiple sex partners as the most important risk factor for these cancers, reports her latest work Nov. 3 in the journal Clinical Cancer Research and in a Centers for Disease Control and Prevention monograph. The CDC report on HPV-associated cancers appears online Nov. 3 and in the Nov. 15 supplement edition of Cancer.

In the CDC report, believed to be the first and most comprehensive assessment of HPV-associated cancer data in the United States, investigators analyzed cancer registry data from 1998 to 2003 and found 25,000 cancer cases each year occurred at cancer sites associated with HPV infection. In additional analysis, Gillison and colleagues at the National Cancer Institute identified HPV infection as the underlying cause of approximately 20,000 of these cancers.

Gillison and her team found that approximately 20,000 cases of cancer in the United States each year are caused by HPV infection. Oral cancers are the second most common type of HPV- associated cancers and are increasing in incidence in the United States, particularly among men. Add to that anal, penile, vaginal and vulvar cancers that are also linked to HPV infection, and Gillison says that these cancers, when combined, equal the number of cervical cancers, the most common and well known of the cancers caused by HPV.

While about one-quarter of HPV-linked cancers occur in men, vaccines are currently approved for use only in girls and young women for cervical cancer prevention. “We need to have a more comprehensive discussion of the potential impact the HPV vaccine could have on cancer rates among men and women in this country,” said Gillison, an associate professor of oncology at Johns Hopkins. “Currently available HPV vaccines have the potential to reduce the rates of HPV-associated cancers, like oral and anal cancers, that are currently on the rise and for which there are no effective or widely applied screening programs.” Gillison said, however, that studies are needed to confirm that the vaccine effectively prevents HPV infections that lead to oral and anal cancers.

Gillison’s findings were part of a project known as ABHACUS, for Assessing the Burden of HPV- Associated Cancers in the United States. The data studied came from the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and End Results program. More than 80 investigators from across the country participated in the project, which addressed a variety of HPV cancerÐassociated issues, including racial disparity, economic impact, behavioral risk factors and cancer mortality.

Other than prevention, early detection is held by cancer experts as the best way to control cancer. In the Clinical Cancer Research study, the first to track the disease and related oral infections over an extended period, Gillison found that simple “swish and spit” oral rinses can successfully track oral HPV infection over time. These findings open the door to a potential noninvasive screening test to detect the disease and monitor for tumor recurrence. Head and neck cancer is the broad term for a variety of cancers of the oral cavity, including the tonsils, base of the tongue and the side and back walls of the throat.

The study found that oral rinses successfully detected high-risk HPV infections in patients with HPV 16 positive head and neck cancers for up to five years after treatment for their cancer. Gillison said that the findings indicate a high rate of persistent infection and reaffirm the connection between high-risk types of HPV and HPV-positive head and neck cancers.

In the study, the researchers used oral rinses to collect cells shed from inside the mouths of 135 head and neck cancer patients. The researchers genetically sequenced the DNA obtained from the rinses and tumor samples to identify those with HPV-positive cancers and determine the HPV type. There are approximately 120 types of HPV, but HPV 16 is one of the two most common associated with cancer.

The analysis revealed 44 patients with HPV 16-positive tumors and found that these patients were more likely to have continuing oral HPV 16 infections both before and after cancer treatment. While this study did not link the continued post-treatment infections to tumor recurrence, it was noted that patients with high-risk oral HPV infections prior to therapy maintained high rates of infection after completing therapy. The team plans further long-term research to determine if this continued infection leads to cancer recurrence.

In 2000, Gillison identified HPV-positive head and neck cancer as a distinct subtype of the disease and linked it to improved survival.

“There is no question of cause,” Gillison said. “It has now become a question of tracking the infection over time to identify those at risk of developing cancer or cancer recurrence.”

Other researchers participating in the study were Yuri Agrawal, Wayne M. Koch, Weihong Xiao, William H. Westra and Anna L. Trivett, all of Johns Hopkins; and David E. Symer, of NCI.

Note:
1. The research was funded by the Oral Cancer Foundation, the National Institute of Dental and Craniofacial Research and the National Cancer Institute.

March, 2010|Oral Cancer News|

Oral sex can add to risk of HPV positive cancers

Source: www.time.com
Author: Coco Masters

Oral sex can get most men’s attention. The topic becomes considerably more relevant, however, when coupled with a new study linking the human papillomavirus (HPV) to an increased risk of a kind of oral cancer more often seen in men.

The study, which appears in this week’s New England Journal of Medicine (NEJM), shows that men and women who reported having six or more oral-sex partners during their lifetime had a nearly ninefold increased risk of developing cancer of the tonsils or at the base of the tongue. Of the 300 study participants, those infected with HPV were also 32 times more likely to develop this type of oral cancer than those who did not have the virus. These findings dwarf the increased risk of developing this so-called oropharyngeal cancer associated with the two major risk factors: smoking (3 times greater) or drinking (2.5 times greater). HPV infection drives cancerous growth, as it is widely understood to do in the cervix. But unlike cervical cancer, this type of oral cancer is more prevalent in men.

HPV is ubiquitous. Of the 120 strains isolated from humans — about 40 of which are in the mouth and genital tracts — Merck’s recently FDA-approved vaccine, Gardasil, protects against four: HPV-6 and HPV-11, which cause warts; and HPV-16 and HPV-18, which cause about 70% of cervical cancers. Similarly, according to the study, HPV-16 was present in 72 of the 100 cancer patients enrolled in the study. Between 12,000 and 15,000 new cases of oropharyngeal cancer are diagnosed each year, and about 3,000 people die from it. “It is a significant health issue,” says Dr. Robert Haddad, clinical director of the Head and Neck Oncology Program at the Dana-Farber Cancer Institute. Haddad says that public awareness of the HPV virus needs to be just like that of HIV because the virus causes multiple types of cancer.

The study’s findings bring to light a part of the debate over HPV vaccination and treatment that is often overlooked: the elevated risks of cancer that being HPV-positive has for men. According to Johns Hopkins’ researcher Dr. Maura Gillison, who worked on the study: “When you look at the cancers associated with HPV in men — including penile cancer, anal squamous cell carcinoma, oral cancers — it’s very close to the number of cases of cervical cancer that occur in the U.S. in women every year. We need to adjust the public’s perception… that only women are at risk.”

hpv_vaccine_0511

In his practice, Haddad has seen an increase in the number of younger people developing this cancer, people in their 30s and 40s. He attributes it in part to a “change in sexual behavior over the last decade.” He says: “The idea that oral sex is risk-free is not correct. It comes with significant risks, and developing cancer is one of them.”

Gardasil has become a vaccine rock star, but vaccines to fight HPV are still in their infancy. Another study in this week’s NEJM points out that while the preventative vaccine works 98% of the time to protect girls not yet infected with HPV-16 and HPV-18, the vaccine is only 17% effective against cancer precursors overall. These findings could undercut the argument ensuing in more than 15 states to make the vaccine mandatory for young girls.

Gardasil and some vaccines in clinical trial are preventative, but drug companies such as MGI Pharma are studying therapeutic vaccines to treat those already infected with the virus. “We need to come up with better vaccines — and we need to study them in men,” says Haddad. Gardasil has not been tested against oral HPV, but Dr. Douglas Lowy, laboratory chief at the National Cancer Institute, says that there is every reason to think that, in principle, “the vaccine should be able to have an impact on oral cancers attributable to HPV.” Lowy says that the next studies might start with a look at the rate of acquisition of oral HPV in those who are vaccinated and those who aren’t.

“There’s no question that the debate needs to go further than where it is now,” says Haddad. “Men are carriers and that is one way of transmitting this virus.”

March, 2010|Oral Cancer News|

OralDNA Labs introduces OraRisk HPV salivary diagnostic test

Source: www.rdhmag.com
Author: press release

OralDNA Labs , a leader in advancing wellness in dentistry through salivary diagnostics and a subsidiary of Quest Diagnostics, recently introduced a OraRisk HPV test.

The test is a noninvasive, screening tool to identify the type(s) of oral human papillomavirus (also called HPV). Oral HPV is a mucosal viral infection that is a known risk factor for oral, head, and neck cancers.

High-risk types of HPV that persist present an increased risk for cancers in these regions. This test will provide the dental clinician with the ability to establish risk for HPV-related cancers of the oral, head, and neck regions, and determine appropriate referral and monitoring conditions.

Squamous cell carcinoma of the head and neck, which can be found in the oral cavity, tongue, tonsils, oropharynx, and larynx, affects approximately 40,000 individuals in the United States each year.

The most common symptoms of SCCHN include sore throat, earache, hoarseness–and often–enlarged lymph nodes in the neck. Early detection of oral HPV presents an important opportunity to detect those at risk for these types of cancers before symptoms appear.

According to OralDNA Labs’ Medical Director Ronald C. McGlennen, MD, “The availability of the OraRisksm HPV test marks an important and timely advance in oral diagnostics, because the at-risk profile for oral cancer is rapidly changing.”
The use of tobacco and heavy alcohol consumption has traditionally been considered to be the primary risk factor for SCCHN, but an alarming number of new cases are being diagnosed each year among persons who do not fit the tobacco and alcohol user profile.

“In fact, a new high-risk profile for SCCHN has emerged,” explained Dr. McGlennen. “Recent research studies have identified several high-risk strains of the human papillomavirus, especially the variant known as HPV-16, as potential etiologic agents in the development of SCCHN.”

It is now estimated that 50% of all diagnosed cases of oral cancer in the United States are attributed to the HPV virus. It has been well documented that HPV transmission is associated with sexual contact with the risk of contracting HPV higher among those with multiple sex partners.

“Oral HPV is a silent, serious infection that can now be detected and closely monitored by the dental professional,” stated OralDNA Labs’ Chief Dental Officer, Thomas W. Nabors, DDS.

“Specifically, the laboratory report derived from the OraRisksm HPV salivary diagnostic test helps dental professionals identify the specific types(s) of oral HPV present, as well as the associated risk profile for each type of HPV variant detected in the patient’s oral cavity.”

Strong candidates for the OraRisksm HPV test include patients with the following profile characteristics:
* Sexually active
* Family history of oral cancer
* Signs and symptoms of oral cancer
* Traditional risk factors for oral cancer
* Suspicious oral lesions

Salivary diagnostic tests from OralDNA Labs are fundamental elements of a patient’s wellness plan. OraRisksm HPV is the third molecular salivary DNA test that OralDNA Labs has introduced to the dental profession in less than a year. In 2009, the company launched two tests for periodontal disease named MyPerioPath and MyPerioID PST.

Specifically, MyPerioPath identifies the type and concentration of specific perio-pathogenic bacteria that are known to cause periodontal disease and helps support clinicians with better risk assessment and personalized treatment options for more predictable patient outcomes.

MyPerioID PST identifies an individual’s genetic susceptibility to periodontal disease and enables clinicians to establish which patients are at increased risk for more severe periodontal infections due to an exaggerated immune response.

March, 2010|Oral Cancer News|

New vaccine against HPV approved in Canada

Source: www.ctv.ca
Author: staff

Canadian women have a choice of two vaccines against HPV, the family of viruses that can cause cervical cancer, now that Health Canada has approved GlaxoSmithKline’s vaccine, Cervarix.

The vaccine, which is expected to be available by the end of the month, will compete against Gardasil, a product of Merck Canada, which has been on the Canadian market since 2006.

Cervarix has been available in Europe since 2007, and was approved in the U.S. this past fall. Health Canada said its approval was based on a review of clinical trials on nearly 30,000 women.

The competing vaccines will be similarly priced, at about $400. Each vaccine requires three doses and are meant for girls and women aged 10 to 25, ideally before they become sexually active.

While there are differences between the two vaccines, each offers good protection against infection with the most dangerous strains of HPV, the Society of Gynecologic Oncology of Canada (GOC) said in a statement Tuesday. The GOC added that each vaccine has had an excellent safety profile both in pre-market testing and after extensive use worldwide.

Cervarix is designed to protect against two human papillomavirus strains: HPV 16 and 18. Those strains are responsible for more than 70 per cent of cases of cervical cancer.

It also offers some protection against three other cancer-causing strains HPV 31, 33 and 45. Between them, the four strains account for more than 80 per cent of cervical cancer cases.

Gardasil also prevents infection with four strains of HPV 16 and 18, as well as HPV 6 and 11. The latter two strains cause about 90 per cent of cases of genital warts.

In all, there are almost 200 strains of HPV, some that cause common warts on the skin, others that cause genital warts and that are sexually transmitted, and some that cause no symptoms at all.

While a number of strains have linked to cervical cancer, others have been linked to throat cancer, cancer of the head and neck, anal cancer, penile cancer and other cancers of the female genital tract such as vulvar and vaginal cancer.

In Canada, every province and territory now offers school-based HPV vaccination although the age group targeted varies by jurisdiction, from Grade 4 in Quebec through to Grade 8 in Ontario. Currently, all school-based programs use Gardasil. But GSK officials say they are in discussions with several provinces and territories.

The GOC stresses that neither vaccine offers 100 per cent protection and women and sexually active girls should still go for regular Pap screening, regardless of whether they’ve been vaccinated.

“With vaccination, in combination with continued cervical screening, cervical cancer and its precursors are now highly preventable,” the group said in a statement.

In Canada, there are approximately 1,400 new cases of cervical cancer and 420 deaths annually.

February, 2010|Oral Cancer News|

HPV-associated base of tongue squamous cell carcinoma incidence increasing in Sweden

Source: www.hemonctoday.com
Author: staff

The incidence for base of tongue squamous cell carcinoma increased significantly in Sweden between 1998 and 2007, and by 2007, more than 80% of these cases were HPV-positive.

Various studies during the past 20 years have indicated that HPV is a risk factor for oropharyngeal cancer. However, few studies have assessed the specific sub-sites of the oropharynx.

In this study, researchers assessed the increased incidence of base of tongue cancer and the association of HPV in 109 patients diagnosed with base of tongue cancer between 1998 and 2007 in Stockholm, Sweden.

The researchers obtained diagnostic pretreatment paraffin-embedded tumor biopsies from 95 patients. DNA samples were obtained from 30-mcm paraffin-embedded base of tongue biopsy slices. Age at diagnosis ranged from 41 to 85 years.

From 1970 to 2007, the age-standardized incidence of base of tongue squamous cell carcinoma increased from 0.15 per 100,000 person-years between 1970 and 1974 to 0.47 per 100,000 person-years between 2005 and 2007.

HPV DNA was found in 75% of base of tongue cancer cases during this time. Of the HPV-positive tumors, 86% were HPV-16–positive and seven were HPV-33–positive.

During the study period, the incidence of HPV-positive base of tongue cancers persistently increased (see chart). A significant increase was found in the proportion of HPV-positive cancer between 1998 and 2001 compared with 2004 and 2007 (58% vs. 84%; P<.05).

When compared with patients with HPV-negative tumors, patients with HPV-positive tumors were likely to be stage IV (P<.02) and had less advanced T-stage (P<.05 for T2; P<.01 for T3); however, these patients had more advanced N-stage (P<.01 for N0; P<.01 for N2a-c).

Source: Attner P. Int J Cancer. 2010;doi:10.1002/ijc.24994.

February, 2010|Oral Cancer News|

Liverpool scientists working on vaccine for mouth cancer

Source: www.liverpoolecho.co.uk
Author: Liza Williams

ONE central project the scientists and doctors are working on is a vaccine for mouth cancer. Liverpool researchers have found some cases are caused by the HPV virus – the same bug which causes cervical cancer. They have discovered that two-thirds of tonsil cancer tumour samples showed evidence of the HPV-16 gene.

The work is particularly important because the researchers are also seeing the rates of tonsil cancer doubling in non-smokers and non-drinkers – two of the main causes of the disease.

They have found a DNA test helps to predict whether a patient has HPV. This could be used to decide which treatment is best for the patient, because both chemo and radiotherapy are more successful in patients with the virus.

They are now developing a clinical trial for a HPV vaccine for head and neck cancer, like the jab given to teenage girls to prevent cervical cancer.

January, 2010|Oral Cancer News|

Vaccines plus screening could end cervical cancer

Source: www.cancernetwork.com
Author: Fram Lowry

Out with the old and in with the new is a commonly followed maxim in medicine given the rapid pace of developments in diagnosis and treatment. Human papillomavirus vaccines are relative newcomers to the cervical cancer armamentarium, but they cannot be relied on to do the job on their own; screening is still a must.

Richard B. Roden, PhD, from Johns Hopkins University in Baltimore, and Carlos L. Santos, MD, from the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, discussed the merits and drawbacks of HPV vaccines and standard screening during a session on female malignancies at ASCO 2009 in Orlando


Long-term protection

The widespread vaccination of adolescents against HPV will be critical to the eradication of cervical cancer, said Dr. Roden, an associate professor in the department of pathology. “HPV virus-like particle [VLP] vaccines are very effective in preventing genital HPV infection and neoplastic disease,” he explained. “Solid protection has been observed for more than six years after vaccination, suggesting vaccine protection is likely to be long-term, although the need for a booster is not out of the question.”

To date, two HPV vaccines are FDA-approved: Gardasil from Merck, produced in yeast, and Cervarix from GlaxoSmithKline, produced in insect cells. In October 2009, Gardasil was approved by the FDA for use in boys and men (aged 9-26) for the prevention of genital warts caused by HPV-6 and HPV-11.

Both vaccines target HPV-16 and HPV-18, the two most common oncogenic HPV types. Gardasil also targets HPV-6 and HPV-11, which cause benign genital warts.

Two types of trials, efficacy trials and immunogenicity bridging trials, have contributed to the licensing of these HPV VLP vaccines. All of the six efficacy trials have been placebo-controlled (randomized 1:1 between vaccine and placebo) and double-blinded, and they have included young women.

“Some of the results from these trials have been confusing to some people, and that reflects the different types of analyses that were done,” Dr. Roden said. The cohorts analyzed were:

• According to protocol (ATP)
• Intention to treat (ITT)
• Modified intention to treat (MITT)

The most clearcut study results came from ATP trials that were conducted with no protocol violations. Also, the endpoints were not counted until the intervention was completed. In ITT, endpoints were counted from the start of enrollment; these trials offer a better estimation of the impact of general use. Finally, in MITT trials, protocol violations were still counted as were endpoints that occurred after one intervention/dose. In the trials with Gardasil and Cervarix, efficacy in the ATP cohort was consistent and impressive, ranging from 96% to 100%. However, the efficacy dropped off in the MITT cohort: between 94% and 100% for the Gardasil trials and between 76% and 94% for Cervarix trials. Based on MITT/ITT analysis for any HPV type, vaccine efficacy came in at 34% in the FUTURE I study, 17% in the FUTURE II study, and 52% in the GSK 001/07 study.

“Why is this efficacy so low? These are really the expected results. The prophylactic vaccine produces somewhat type-restricted protection,” Dr. Roden said. “The vaccine does not induce the regression of established infection. Disease from prevalent infection dominated disease from incident infection in the trials that had a relatively short follow up.” In short, the vaccines are not therapeutic, he added.

The HPV vaccine has been shown to be effective in other groups, Dr. Roden said. ATP data on Gardasil have demonstrated a 90% reduction in HPV-6 and HPV-11 in women aged 24 to 45. It has also been deemed effective in adolescent boys and men (aged 16 to 23), with an approximately 85% reduction in incident, persistent six-month infection and a near 90% reduction in incident external warts caused by the main HPV types.

Finally, immunobridging studies provide rationale for vaccination in groups that were not included in the major trials, such as adolescent girls, he said. Solid protection for more than six years after vaccination suggests that the benefits are long-term.

Screening remains main option in many countries
While the evidence for the efficacy of vaccination may be solid, its widespread, global distribution is less certain at this time. In developing areas with limited resources, vaccination with the current HPV vaccines may not be an option, said Dr. Santos, who is a gynecologic oncologist at his institution. This is particularly problematic because cervical cancer is prevalent in these areas, with the highest incident mortality rates in sub-Saharan Africa, Latin America, and some Asian countries, Dr. Santos said. In half of Latin American countries, cervical cancer is the number one female malignancy.

“Let’s take a look at the development of cervical carcinogenesis in order to understand the place for secondary prevention,” he said. “This is a long-lasting process, starting with HPV infection and ending up in invasive carcinoma capable of killing the host. Fortunately, we have a long period of precancerous or premalignant lesions, usually five to 15 years, and these are easily treatable.”

There are two ways to establish a cervical cancer screening program, Dr. Santos said. An opportunistic program takes advantage of any visit that a female patient makes within her healthcare system as a chance for screening. An organized program is promoted by a central public health institution, which ensures coverage to all at risk.

The standard methodology for screening is cytology, followed by colposcopy if it is deemed necessary, followed by biopsy. This system has proved very effective in industrialized nations, Dr. Santos pointed out. He cited data from Scandinavia as an example. “Sweden and Finland get the best results in terms of reduction of the mortality rate because they have long-standing and very well organized screening programs,” he said. “Norway started screening a bit later compared to its neighbors. In Denmark, there is a mixture of opportunistic and organized screening and their results are not as good.”

Unfortunately, developing nations cannot claim such success rates, Dr. Santos said. Some of the reasons that screening has failed include:

• Failure to reach the population at risk
• Lack of sensitivity of cytologic screening
• Infrequency of repeated screening
• Inadequate management of abnormalities found at screening
• Ineffective treatment

However, some countries are having success with screening programs that work outside the confines of traditional, cytology-based methods. In Peru, a “see and treat” approach has been effective, Dr. Santos said. The 10-minute screening starts with the application of a solution of 5% acetic acid on the cervix, which will demarcate the borders of any lesion in the transformation zone. Any lesions that are found are considered high-grade and are treated immediately with cryotherapy, he said, adding that the advantage of cryotherapy is that it is an outpatient procedure that requires no anesthesia.

While HPV vaccination may not happen in developing nations for some time, HPV DNA testing is coming to the forefront as the primary screening method. HPV DNA testing offers many advantages, according to Dr. Santos. “It has a sensitivity over 95%, although it is less specific than cytology,” he said. “Another virtue of HPV DNA testing is that it has very good predictive value: having a negative HPV test means that there is little or no probability of developing a lesion in the next 10 years.”

The obstacle to using HPV testing in the developing world is cost, with the price tag on an individual test ranging from $70 to $80. But a less expensive reliable test—the careHPV at $5 per test—is on the horizon, Dr. Santos said. “This is the plan for developing countries. Women will be screened with careHPV. Those with negative studies will return in three to five years for follow-up testing. Those with positive results will be triaged the same day to visual inspection, and if necessary, will be treated with cryotherapy.”

Even after HPV vaccination goes global, screening will still be necessary, he said. Women who have been vaccinated will undergo screening with HPV DNA testing or biomarker testing later in life (around age 30), and the interval between screenings may be as long as a decade, Dr. Santos predicted.

December, 2009|Oral Cancer News|

Cervarix® vaccination against HPV lasts at least six years

Source: professional.cancerconsultants.com
Author: staff

Researchers affiliated with the GlaxoSmithKline Vaccine HPV-007 Study Group have reported that Cervarix® [human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine] has “high and sustained immunogenicity, and a favorable safety” profile for up to 6.4 years following administration. The details of this study appeared in an early online publication in the Lancet on December 3, 2009.[1]

Cervarix is approved by the U.S. Food and Drug Administration for the prevention of cervical pre-cancers and cervical cancer associated with HPV types 16 and 18. It is approved for use in girls and women between the ages of 10 and 25 years.

Human papillomaviruses consist of more than 100 different viruses. Some types of HPV cause warts on the hands or feet; others cause genital warts; and some have been linked with cancer, most notably cervical cancer. The types of HPV most commonly linked with cervical cancer are HPV 16 and HPV 18, but several other high-risk types contribute to cancer as well.

The types of HPV that cause cervical cancer or genital warts are transmitted sexually. HPV infection is extremely common and generally occurs soon after an individual becomes sexually active. Although most infections resolve on their own, some persist and can lead to precancerous or cancerous changes to the cervix, vulva, vagina, penis, and anus. HPV infections have also been linked with some head and neck cancers.

The first HPV vaccine to be approved in the United States was Gardasil®, which protects against HPV types 6 and 11 (linked to genital warts), as well as the cancer-associated types 16 and 18. Cervarix also protects against HPV types 16 and 18. Both Gardasil and Cervarix are intended to prevent infection with certain types of HPV and do not treat existing HPV infections or cervical abnormalities. It’s also important to keep in mind that these vaccines do not protect against all types of HPV; women who are vaccinated should continue to be screened for cervical cancer.

The current report presents the results of follow-up analyses of young women participating in two randomized controlled trials of Cervarix for prevention of cervical cancer with follow-ups extending to 6.4 years. These authors reported that prevention of HPV 16/18 was 95.3% and prevention of persistent infection was 100%. Cervarix was 100% effective in preventing cervical intraepithelial neoplasia (CIN) 2+ associated with HPV 16/18in young women. Cervarix was 72% effective in preventing lesions independent of HPV DNA. They also reported that antibody concentrations remained 12 times higher than in control women. There were also no more side effects to the vaccine than to the placebo.

Comments:
This is important information, as durability of vaccination is a necessity for application to underdeveloped countries, where the risk of cervical cancer is the highest. An accompanying editorial suggests that this new information provides an impetus to develop methods to vaccinate more young women before sexual activity in order to prevent the 0.5 million new cases of cervical cancer that occur worldwide each year.[2]

References:
[1] The GlaxoSmithKline HPV-007 Study Group. Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years. Lancet [early online publication]. December 3, 2009.

[2] Clifford GM. Global access to HPV vaccination: what are we waiting for? Lancet [early online publication]. December 3, 2009.

December, 2009|Oral Cancer News|