Extra Protection: New HPV Vaccine Extends Protection to Nine Strains of The Virus

 

By Asu Erden

The human papillomavirus (HPV) is responsible for 5% of all cancers. Until, 2006 there were no commercially available vaccines against the virus. That year, the Food and Drug Administration (FDA) approved the first preventive HPV vaccine, Gardasil (qHPV). This vaccine conveys protection against strains 6, 11, 16, and 18 of the virus and demonstrates remarkable efficacy. The Centers for Disease Control (CDC) estimates that this quadrivalent vaccine prevents 100% of genital pre-cancers and warts in previously unexposed women and 90% of genital warts and 75% of anal cancers in men. While this qHPV protects against 70% of HPV strains, there remains a number of high-risk strains such as HPV 31, 35, 39, 45, 51, 52, 58 for which we do not yet have prophylactic vaccines.

 

In February of this year, a study by an international team spanning five continents changed this state of affairs. The team led by Dr. Elmar A. Joura, Associate Professor of Gynecology and Obstetrics at the Medical University, published its study in the New England Journal of Medicine. It details a phase 2b-3 clinical study of a novel nine-valent HPV (9vHPV) vaccine that targets the four HPV strains included in Gardasil as well as strains 31, 33, 45, 52, and 58. The 9vHPV vaccine was tested side-by-side with the qHPV vaccine in an international cohort of 14, 215 women. Each participant received three doses of either vaccine, the first on day one, the second dose two months later, and the final dose six months after the first dose. Neither groups differed in their basal health or sexual behavior. This is the immunization regimen currently implemented for the Gardasil vaccine.

 

Blood samples as well as local tissue swabs were collected for analysis of antibody responses and HPV infection, respectively. They revealed the same low percentage of high-grade cervical, vulvar, or vaginal. Antibody responses against the four HPV strains included in the Gardasil vaccine were similar in both treatment groups. Of note is that participants in the 9vHPV vaccine group experienced more mild to moderate adverse events at the site of injection. Dr. Elmar A. Joura explained that these effects are due to the fact that the “[new] vaccine contains more antigen, hence more local reactions are expected. The amount of aluminium [editor’s note: the adjuvant used in the vaccine] was adapted to fit with the amount of antigen. It is the same amount of aluminium as used in the Hepatitis B vaccine.”

 

These results confirm that the novel 9vHPV vaccine raises antibody responses against HPV strains 6, 11, 16, 18 that are as efficacious as the original Gardasil vaccine. In addition, the novel vaccine also raises protection against HPV strains 31, 33, 45, 52, and 58. Importantly, the immune responses triggered by the 9vHPV vaccine are as protective against HPV disease as those raised by the qHPV vaccine.

 

Yet we are all too familiar with the contention surrounding the original qHPV vaccine. And no doubt, this new 9vHPV vaccine will reignite the debate. Those who specifically oppose the HPV vaccine question its safety and usefulness. In terms of its safety, the HPV vaccine has been tested for over a decade prior to becoming commercially available and has been proven completely safe since its introduction a decade ago. Adverse effects include muscle soreness at the site of injection, which is expected for a vaccine delivered into the muscle…

 

As for its usefulness, don’t make me drag the Surgeon General and Elmo onto the stage. The qHPV vaccine has been shown to be safe and to significantly impact HPV-related genital warts, HPV infection, and cervical complications, “as early as three years after the introduction of [the vaccine]” in terms of curtailing the transmission and public health costs of HPV infections and related cancers.   “HPV related disease and cancer is common. It pays off to get vaccinated and even more importantly to protect the children,” noted Dr Elmar A. Joura.

 

Other opponents to the HPV vaccines raise concerns regarding the use of aluminium as the adjuvant in the formulation of the vaccine. This inorganic compound is necessary to increase the immunogenicity of the vaccine and for the appropriate immune response to be raised against HPV. Common vaccines that include this adjuvant include the hepatitis A, hepatitis B, diphtheria-tetanus-pertussis (DTP), Haemophilus influenzae type b, as well as pneumococcal vaccines.

 

The only question we face is that given the availability of Gardasil, why do we need a nine-valent vaccine? In order to achieve even greater levels of protection in the population at large, extending coverage to additional high-risk HPV strains is of central importance for public health. The team of international scientists that contributed to the study underlined that the 9vHPV vaccine “offers the potential to increase overall prevention of cervical cancer from approximately 70% to approximately 90%.” Thus the novel 9vHPV vaccine offers hope in bringing us even closer to achieving this epidemiological goal. “With this vaccine cervical and other HPV-related cancers could potentially get eliminated, if a good coverage could be achieved. This has not only an impact on treatment costs but also on cervical screening algorithms and long-term costs,” highlighted Dr. Elmar A Joura.

Cancer DNA: The New Frontier for Preventing and Curing Cancer

By Jesica Levingston Mac Leod, PhD

 

DNA Biomarkers are the hot topic in oncology right now, and the more precise, easy and effective they may be to detect cancer, the better.  This cutting edge technique has its origins in the discovery that fetuses shed fragments of DNA into the bloodstreams of the mothers, so do normal and cancer cells. The strategy to search for the most accurate “bar code” for each type of cancer is been approach from a bunch of oncologists around the world.

Researchers from the National Cancer institute, MD, published this month in the Lancet, a correlative biomarker study for lymphoma. In the study publish by Roschewski and col., they detected circulating tumor DNA encoding the clonal immunoglobulin gene sequence (VDJ) in the serum of patients with diffuse large-B-cell lymphoma. The VDJ immunoglobulin genes contain unique sequences that are markers of clonality. Malignant cell VDJ gene sequences could be detected in the serum of patients with diffuse large B-cell lymphoma and used to predict clinical disease recurrence after treatment. For this, they used next-generation DNA sequencing to analyze cell-free circulating tumor DNA in patients assigned to one of three different treatment protocols during a period of 20 years. They concluded that “Surveillance circulating tumor DNA identifies patients at risk of recurrence before clinical evidence of disease in most patients and results in a reduced disease burden at relapse. Interim circulating tumor DNA is a promising biomarker to identify patients at high risk of treatment failure.”

Earlier this year, Hyman and col., reported the analysis of a biomarker (the mutant BRAF(V600E)) in 2 systemic histiocytic disorders characterized by accumulation and infiltration of histiocytes in multiple tissues of the body, leading to organ compromise. These researchers from Memorial Sloan Kettering Cancer Center, New York, showed that in plasma and urinary samples cell free DNA provides a reliable method to detect the mutation that is a biomarker for these disorders, and it can monitor response to therapy in these disorders.

In Australia, the group of doctors  Tie, Cosgrove and col., identified and validated 3 protein-based biomarkers in independent cohorts of colorectal cancer (n = 145 and n = 197), which could be translated to a reliable, non-invasive blood-based screening test. The biomarker “winners” were selected by Elisa kits, and they are the following proteins: Insulin like growth factor binding protein 2 (IGFBP2), Dickkopf-3 (DKK3), and Pyruvate kinase M2(PKM2). (3) Anyways, this article is bout DNA markers: So, in a follow up study Tie and col. detected circulating tumor DNA in a high proportion of treatment naïve metastatic colorectal cancer patients. Moreover, they described that early changes in circulating tumor DNA during first-line chemotherapy predict the later radiologic response.  On other notes, they also reported that the intake of aspirin is not associated with improvements in survival in colon cancer patients, yeah, bad news for the daily aspirin takers.

Studying the blood samples of healthy elders (“wellderlies”, adults age 80 plus), the team lead by doctor Eric Topol, at the SCRIP center, is trying to find the immune response that attacked and effectively destroyed cancer cells. There is a high probability that these healthy elders had had abnormal cell/cells in their bodies at some point of their lives, which they attacked and destroyed, generating immune memory and powerful anti-cancer antibodies. In fact, a member of the team, Doctor Brunie Felding, had discovered that one of the proteins recognized by “wellderly” antibodies was Apolipoprotein E, suggesting that antibodies against this protein may help develop a targeted therapy against highly-expressing ApolipoproteinE cancers.

These new discoveries, plus the recently  FDA approval of three new immuno-oncology therapy drugs, called PD-1 inhibitors,  are bright examples of the importance of cancer research funding and support from the public to the government officers.

One of the most influential bioinformaticians/molecular biologists, Dr. George Church, genetics professor at Harvard, thinks that “the DNA is the ultimate computer code and we are all computer programmers”. Therefore, the study of the DNA fragments can help to solve multiple problems… it is working for cancer therapy, and it could be useful to treat even the most common disease: aging.