Head and Neck Cancer Survivors at Risk of Secondary Cancers, esp if They Smoke

MedicalResearch.com Interview with:

Eric Adjei Boakye, PhD, MA Saint Louis University Center for Health Outcomes Research (SLUCOR) St. Louis, Missouri

Dr. Boakye

Eric Adjei PhD, MA
Saint Louis University Center for Health Outcomes Research (SLUCOR)
St. Louis, Missouri 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Survivors of head and neck cancer (HNC) develop second primary cancers (SPCs) at a higher rate than most common cancers. This is concerning because the number of HNC survivors are increasing due to advancements in treatment and technology. Patients whose head and neck cancer was caused by smoking and alcohol are different than those whose HNC were caused by human papillomavirus (HPV). We therefore used data from 2000-2014 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) 18 database to examine if the incidence and the type of SPC that patients with smoking-related HNC develop were different from those from HPV-related head and neck cancer.

First, independent of group of HNC (HPV-related or not), we found that SPCs among survivors of head and neck cancer were high, with about 1-in-8 patients developing an SPC. Additionally, irrespective of whether the index . head and neck cancer was from smoking-related or HPV-related, the majority of SPCs were second malignancies in head and neck region (e.g. tongue, gum, mouth floor etc), lung and esophagus. However, we observed different incidence rates between the two groups. Patients with smoking-related head and neck cancer developed SPCs at a higher rate (14%) than those with HPV-related HNC (10%).

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HPV Testing Detects Cervical Pre-Cancer Earlier Than PAP Tests

MedicalResearch.com Interview with:

Gina Ogilvie | MD MSc FCFP DrPH Professor | Faculty of Medicine | University of British Columbia Canada Research Chair | Global control of HPV related disease and cancer Senior Public Health Scientist | BC Centre for Disease Control Senior Research Advisor | BC Women's Hospital and Health Centre BC Women's Hospital and Health Centre Vancouver, BC

Dr. Gina Ogilvie

Dr. Gina Ogilvie | MD MSc FCFP DrPH
Professor | Faculty of Medicine | University of British Columbia
Canada Research Chair | Global control of HPV related disease and cancer
Senior Public Health Scientist | BC Centre for Disease Control
Senior Research Advisor | BC Women’s Hospital and Health Centre
BC Women’s Hospital and Health Centre
Vancouver, BC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: HPV is known to be the cause of 99% of cervcial cancers.

In this study, we compared the routine screening test for cervical cancer, Pap test, to HPV testing.

We found that by using HPV testing, women were significantly more likely to have cervical pre-cancers detected earlier. In addition, women with negative HPV tests were significantly less likely to have pre-cancers 48 months later.

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Potentially Cancerous Genital Lesions Common in Transplant Population

MedicalResearch.com Interview with:

Dr. Christina Lee Chung, MD Associate Professor Department of Dermatology Drexel University

Dr. Chung

Dr. Christina Lee Chung, MD
Associate Professor
Department of Dermatology
Drexel University

MedicalResearch.com:  What is the background for this study?  What are the main findings?

Response: In early 2016, five years after the inception of our specialty medical-surgical transplant dermatology center, we realized our nonwhite transplant patients were developing skin cancer at higher rates and found interesting trends. These data were published in a previous manuscript. One of the more striking findings was that these patients were developing a high proportion of skin cancer in non-sun-exposed areas such as the genital region. There are no standard guidelines regarding genital skin evaluation and it is unclear how often it is performed in any capacity amongst dermatologists, including practitioners in our center, quite frankly. Our group was concerned that we could be missing skin cancers in this “hidden” area in our high-risk organ transplant population so we launched a quality improvement initiative that incorporated thorough genital skin evaluation as a standard part of post-transplant skin cancer screening.   

Fifteen months after we started this modified screening process, we decided to evaluate the results. To account for any variation in examination, we looked at the findings of a single practitioner.

We found that genital lesions are common in the transplant population and include high rates of genital warts and skin cancer. However, patient awareness of the presence of genital lesions was alarmingly low. Nonwhite transplant patients, Black transplant recipients in particular, were disproportionately affected by both genital warts and genital skin cancer in our cohort. Similar to cervical cancer, high-risk HPV types were closely associated with genital squamous cell carcinoma development in our transplant population. Continue reading

Cancer in Young Adults Disproportionately Affects Women

MedicalResearch.com Interview with:

Dr Miranda M Fidler, PhD Section of Cancer Surveillance International Agency for Research on Cancer Lyon, France 

Dr. Fidler

Dr Miranda M Fidler, PhD
Section of Cancer Surveillance
International Agency for Research on Cancer
Lyon, France 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The burden of cancer among young adults has been rarely studied in depth. To our knowledge, we describe for the first time the scale and profile of cancer incidence and mortality worldwide among 20-39 year-olds, highlighting major patterns by age, sex, development level, and geographic region.

Although cancer is less frequent than that observed at older ages, its impact remains considerable because these individuals have a large proportion of their expected lifespans remaining, contribute substantially to the economy, and play a major role in caring for their families. Worldwide, almost 1 million new cases of cancer and 400 000 cancer-related deaths occurred among young adults aged 20–39 years in 2012.

Overall, the most common cancer types in terms of new cases were female breast cancer, cervical cancer, thyroid cancer, leukemia, and colorectal cancer, and the most common types of cancer-related deaths were those due to female breast cancer, liver cancer, leukemia, and cervical cancer. The burden was disproportionately greater among women, with an estimated 633 000 new cancer cases (65% of all new cancer cases in that age group) and 194 000 cancer-related deaths (54% of all cancer-related deaths in that age group) in 2012.

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Oropharyngeal Cancer Rising In Incidence and Costs to Over $140,000

MedicalResearch.com Interview with:

David R. Lairson, PhD Professor of Health Economics Division of Management Policy and Community Health Co-Director, Center for Health Services Research School of Public Health The University of Texas Health Science Center at Houston (UTHealth)

Dr. Lairson

David R. Lairson, PhD
Professor of health economics
Department of Management, Policy, and Community Health
The University of Texas Health Science Center at Houston (UTHealth) School of Public Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The study of oropharyngeal cancer treatment cost was initiated by the Head and Neck Cancer Surgery Department at the University of Texas MD Anderson Cancer Center as part of a larger study of the economic and health consequences of human papillomavirus (HPV) related conditions in Texas.  State specific information is required for policy-makers to consider future investments in cancer prevention based on HPV immunization and cancer screening.  The cost estimates at $140,000 per case for the first two years of treatment are substantially higher than previous estimates.  They indicate the potential savings associated with cancer prevention and partially justify increased investment in immunization efforts.

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Increase in HPV+ Oropharyngeal Cancers Suggests Both Sexes Should Be Vaccinated

MedicalResearch.com Interview with:

Steven Habbous MSc, PhD candidate Ontario Cancer Institute Scarborough, Ontario, Canada

Steven Habbous

Steven Habbous MSc, PhD candidate
Ontario Cancer Institute
Scarborough, Ontario, Canada

MedicalResearch.com: What is the background for this study?

Response: Human papillomavirus (HPV) is a strong risk factor for oropharyngeal cancers (a subset of head and neck cancers). Because HPV-related oropharyngeal cancers generally respond well to treatment and may be prevented through HPV vaccination, it is critical to be able to accurately estimate the incidence and prevalence of this disease. Only recently, however, has testing for HPV become routine at most cancer centres across Canada.  As a result, attempts to estimate the growth of HPV-related oropharyngeal cancer over time may be inaccurate.

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How Does HPV Virus Lead To Skin Cancer?

MedicalResearch.com Interview with:
Prof. Dr. med. Sigrun Smola
Institute of Virology, Saarland University
Homburg/Saar, Germany

MedicalResearch.com: What is the background for this study?

Response: Non-melanoma skin cancer (NMSC), the most common cancer in humans, is caused by UV-irradiation. The potential co-factor role of cutaneous genus beta-human papillomaviruses (beta-HPV) in skin carcinogenesis, particularly in immunosuppressed patients, has become a major field of interest. However, the underlying mechanisms were unclear.

The skin has natural mechanisms providing protection against UV-induced damage. One important factor suppressing UV-induced skin carcinogenesis is the transcription factor C/EBPα belonging to the CCAAT/enhancer binding protein family. C/EBPα can induce cellular differentiation and is regarded as a tumor suppressor in various tissues. When C/EBPα expression is blocked in these tissues, tumorigenesis is enhanced.

Another important factor is the microRNA-203. It has been shown to control “stemness” in normal skin by suppressing a factor called p63. In many tumors miR-203 expression is shut off releasing this “brake”.

In our study we demonstrate that cutaneous beta-HPV interferes with both protective factors providing an explanation how cutaneous beta-HPV enhances the susceptibility to UV-induced carcinogenesis. Moreover, we provide evidence that these viruses regulate miR-203 via C/EBPα.

We have investigated this mechanism in Epidermodysplasia verruciformis (EV) patients that serve as a human model disease for studying the biology of genus beta-HPVs. They are highly susceptible to persistent genus beta-HPV infection, such as HPV8, and have an increased risk to develop non-melanoma skin cancer at sun-exposed sites.

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Quadrivalent HPV Vaccination and the Risk of Adverse Pregnancy Outcomes

MedicalResearch.com Interview with:
Anders Hviid

Senior Investigator, M.Sc.,Dr.Med.Sci.
Department of Epidemiology Research
Division of National Health Surveillance & Research

MedicalResearch.com: What is the background for this study?

Response: HPV vaccination targeting girls and young women has been introduced in many countries throughout the world. HPV vaccines are not recommended for use in pregnancy, but given the target group, inadvertent exposure will occur in early unrecognized pregnancies. However, data on the safety of HPV vaccination in pregnancy is lacking.
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Pubic Hair Grooming Linked To Increased Risk of STDs

MedicalResearch.com Interview with:

E. Charles Osterberg, M.D. Assistant Professor of Surgery Genitourinary Reconstruction and Trauma University of Texas- Dell Medical School Dell-Seton Medical Center / University Hospital

Dr. Osterberg

E. Charles Osterberg, M.D.
Assistant Professor of Surgery
Genitourinary Reconstruction and Trauma
University of Texas- Dell Medical School
Dell-Seton Medical Center / University Hospital

MedicalResearch.com: What is the background for this study?

Response: Pubic hair grooming has become an increasingly common practice among men and women. Perceptions of genital normalcy have changed as modern society’s definition of attractiveness and feelings of femininity and masculinity have changed. Pubic hair grooming has been shown to increase morbidity such as genital injuries, however little is known about the relationship between grooming practices and sexually transmitted infections.

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Epidemic of HPV Associated Throat Cancer in Men

MedicalResearch.com Interview with:

Eric M Genden, MD, FACS Isidore Friesner Professor and Chairman Department of Otolaryngology-Head and Neck Surgery The Icahn School of Medicine at Mount Sinai

Dr. Eric Genden

Eric M Genden, MD, FACS
Isidore Friesner Professor and Chairman
Department of Otolaryngology-Head and Neck Surgery
The Icahn School of Medicine at Mount Sinai

MedicalResearch.com: What is the background for this report? How has the clinical picture of HPV infections of oral and throat cancers changed over the past two decades?

Response: There has been no change however there has been a epidemic of viral induced throat cancer in men. The HPV virus has been established a the causative agent in cervical cancer in women. It has now been identified as a major causative agent in tonsillar and base of tongue cancer.

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Cell Biomarkers To Distinguish Deadly From Less Aggressive HPV Oral Cancers

MedicalResearch.com Interview with:

Elizabeth Franzmann, M.D. Scientific Founder and Chief Scientific Officer Vigilant Biosciences

Dr. Elizabeth Franzmann

Elizabeth Franzmann, M.D.
Scientific Founder and Chief Scientific Officer
Vigilant Biosciences

MedicalResearch.com: What is the background for this study?

Response: Head and neck cancer involves cancers of the oral cavity, oropharynx and larynx. It is difficult to treat. Part of the challenge is that it is distinguishing the patients with tumors that are going to behave aggressively from those with less aggressive disease. As a result, many patients undergo treatment that may be more intensive and morbid than they need while others need more aggressive treatment. Tissue markers associated with prognosis may be able to help clinicians differentiate patients who need more aggressive treatment from those whose treatment can be less intensive. CD44 is a cell surface glycoprotein and tumor-initiating marker. CD44 and another surface protein, EGFR, are involved in tumor extension and are associated with poor prognosis. Certain forms of Human Papillomavirus (HPV) are known to cause oropharyngeal cancer and are associated with a good prognosis. P16 is a surrogate marker for the kind of HPV that causes cancer. Understanding the relationships between how these markers are expressed in cancer tissue may direct patient treatment in the future.

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HPV-Related Cancers Continue to Risk, Most Preventable With Vaccine

MedicalResearch.com Interview with:
Laura J. Viens, MD
Division of cancer prevention and control
CDC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We analyzed the most recent available data from 2008–2012 from CDC’s National Program of Cancer Registries (NPCR) and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program for HPV-associated cancers.

  • These data cover 99% of the US population.
  • These data represent the official federal statistics on cancer incidence (new cases).
  • Every year between 2008 and 2012, about 39,000 men and women were diagnosed with cancers associated with HPV, an overall increase when compared with the 33,000 cancers associated with HPV between 2004 and 2008.
  • 23,000 (13.5 per 100,000 population) among females and 15,793 (9.7 per 100,000 population) among males.

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Kidney Transplant Patients May Not Be Protected From HPV Strains in Vaccines

MedicalResearch.com Interview with:

Dr. Delphine Robotham MD Division of Pediatric Nephrology Johns Hopkins University School of Medicine Baltimore, Maryland

Dr. Robotham

Dr. Delphine Robotham MD
Division of Pediatric Nephrology
Johns Hopkins University School of Medicine
Baltimore, Maryland

Medical Research: What is the background for this study? What are the main findings?

Response: Cervical cancer is the second most common cancer in women worldwide and is almost entirely caused by high risk HPV genotypes.  Vaccines to high risk HPV genotypes have shown great success in protecting healthy women from the sequelae of infection, including cervical cancer and genital warts. Young women with a kidney transplant as well as those with chronic kidney disease have abnormal immune systems and as a result have a significantly increased burden of HPV-related disease making the potential health benefits of the HPV vaccine substantial in this particularly vulnerable population.  This study examined the immune response to the HPV vaccine among girls and young women with kidney disease.

The goal of this research was to determine if girls and young women with chronic kidney disease (abnormal kidney function, on dialysis, or post kidney transplant) showed evidence of immune response to the quadrivalent HPV vaccine.  Immune response was determined by measuring the amount of antibody made by the patients against each of the 4 HPV genotypes included in the vaccine.  There are established thresholds of antibody above which patients are believed to have protection from infection.  We found that study participants with chronic kidney disease and those on dialysis had antibody levels above the threshold, indicating the vaccine should be effective in protecting them from HPV related disease.  A significant proportion of patients with kidney transplants showed evidence of inadequate antibody response.  This is important information as it means patients with a kidney transplant, whom we know are at increased risk of developing cervical cancer from HPV infection, may not be protected from HPV infections from the HPV genotypes included in the vaccine.
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Hepatitis C Raises Risk of HPV Head and Neck Cancers

MedicalResearch.com Interview with:

Harrys A. Torres, MD, FACP, FIDSA Associate Professor Director of Hepatitis C Clinic Department of Infectious Diseases, Infection Control and Employee Health The University of Texas MD Anderson Cancer Center Houston TX 77030

Dr. Harrys Torres

Harrys A. Torres, MD, FACP, FIDSA
Associate Professor
Director of Hepatitis C Clinic
Department of Infectious Diseases, Infection Control and Employee Health
The University of Texas MD Anderson Cancer Center
Houston TX 77030

Medical Research: What is the background for this study? What are the main findings?

Dr. Torres: Hepatitis C virus (HCV) is an oncogenic virus and is associated with an increased risk of liver cancer and certain types of non-Hodgkin lymphomas. In 2009, at MD Anderson Cancer Center, we set up the first clinic in the United States, and probably in the world, specifically devoted to managing HCV infection in cancer patients. In the clinic, we expected to see a number of patients with liver cancers and non-Hodgkin’s lymphoma, as these have documented associations with HCV. Unexpectedly, we saw a high number of HCV-infected patients with head and neck cancers, and wondered whether there was an undiscovered association between having the infection and head and neck cancers. To explore this, we conducted a case-control study using 409 head and neck cancer subjects (164 oropharyngeal, 245 non-oropharyngeal [oral cavity, nasopharynx, larynx] cancers) and 694 control subjects with other smoking-associated cancers (378 lung, 168 esophagus, and 148 urinary bladder cancers), and compared the prevalence of HCV infection in the two groups. We observed a high prevalence of HCV infection in oropharyngeal (14%) and non-oropharyngeal (20%) cancer patients when compared to control subjects (6.5%). After adjusting for confounders such as smoking, alcohol intake, and socioeconomic status, HCV-infected individuals were 2.04 times more likely to have oropharyngeal cancers and 2.85 times more likely to have non-oropharyngeal cancers. Of note, HCV was associated only with patients with oropharyngeal cancers that tested positive for human papilloma virus, which is one of the main virus linked with increased risk of oropharyngeal cancers.

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Vaginal Ultrasound Probes Should Be Covered With Condom To Reduce HPV Infection Risk

MedicalResearch.com Interview with:
Andrew Combs MD
Alan Fishman MD

Obstetrix Medical Group
San Jose, California

MedicalResearch.com: What is the background for this study?

Response: Vaginal ultrasound is a common procedure in gynecology and obstetrics. To perform vaginal ultrasound, an ultrasound probe is placed in the vagina in order to get a close-up view of a woman’s pelvic organs. In non-pregnant women, this is the preferred method for ultrasound of the uterus and ovaries. In early pregnancy, vaginal ultrasound often yields better images of the developing embryo than abdominal ultrasound. In later pregnancy, vaginal ultrasound gives more accurate pictures of the cervix and placenta than abdominal ultrasound.

In order to prevent transmission of disease from patient to patient, it is mandatory to clean and disinfect the probe after each vaginal exam. The FDA has a list of “high level” disinfectants that neutralize or kill a variety of bacteria and viruses. Several manufacturers make disinfectant systems that are approved for disinfection of ultrasound probes.

It is also mandatory to cover the probe with a barrier during each exam. Various companies manufacture ultrasound probe covers intended to be barriers against infection. 

MedicalResearch.com: What are the main findings?

Response: Recent studies found that two widely-used disinfectants (glutaraldehyde and ortho-ophthalaldehyde) do not neutralize human papilloma virus (HPV) even though they are on the FDA list of high level disinfectants. HPV is the most common sexually transmitted infection in the USA, affecting over 8 million women of reproductive age. HPV is responsible for 60% of cervical cancer worldwide. Clearly, it is critical to neutralize this virus on vaginal ultrasound probes. A different high-level disinfectant system, sonicated hydrogen peroxide, was found to be highly effective at neutralizing HPV.

Other studies show that commercial ultrasound probe covers have a high rate of leakage, 8-81%. Condoms are safer probe covers, with leakage rates of 0.9 to 2%.

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Dual and Concordant Vaginal and Oral HPV Infections in Women

MedicalResearch.com Interview with:

Ryan K. Orosco, MD Division of Head and Neck Surgery Department of Surgery University of California, San Diego

Dr. Ryan Orosco

Ryan K. Orosco, MD
Division of Head and Neck Surgery
Department of Surgery
University of California, San Diego

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Orosco: Our group at UC San Diego is interested in HPV as it relates to diseases of the head and neck.  HPV is a well-publicized cause of cervical cancer, and awareness about its link to throat (oropharynx) cancer is rapidly increasing.

Less well-known, is the relationship between HPV and benign (non-cancerous) diseases such as genital warts and papilloma of the throat.  As we strive to understand how to best care for patients with HPV-related disorders, it is important to understand the entire process of disease progression, which begins with HPV infection. Our group wanted to explore the relationship between HPV infection in the two most commonly infected body sites: oral and vaginal.

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HPV Strains Raise Risk of Head and Neck Squamous Cell Cancer

Ilir Agalliu, M.D., Sc.D. Assistant Professor, Department of Epidemiology & Population Health and Department of Urology Albert Einstein College of Medicine Jack and Pearl Resnick Campus Bronx, NY

Dr. Ilir Agalliu

More on HPV on MedicalResearch.com 

MedicalResearch.com Interview with:
Ilir Agalliu, M.D., Sc.D.
Assistant Professor, Department of Epidemiology & Population Health and Department of Urology
Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
Bronx, NY


Medical Research: What is the background for this study?

Dr. Burk: We performed this study since we had previously detected an unusually high prevalence of HPV types found on the skin and skin cancers in the oral cavity in addition to HPV16 and other high-risk (HR) types (as defined by their association with cervix cancer) (see Journal of Infectious Diseases 204:787, 2011). We wished to determine if these types were associated with risk of head and neck cancers (HNSCCs). In addition, we wished to determine if HPV detection preceded the diagnosis of HNSCCs and might serve as a biomarker. Currently there are no good screening tests for HNSCC.

Dr. AgalliuTo-date, there have been no prospective studies examining the temporal relationship between oral HPV detection and risk of head and neck squamous cell carcinoma (HNSCC). In this manuscript we examined prospectively associations between detection of a wide spectrum of oral HPVs (alpha, beta and gamma) with incident HNSCC in a nested case-control study among ~100,000 participants who provided mouthwash samples in the American Cancer Society-CPS II cohort and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Dr. Agalliu: Oral HPV16 detection, which preceded cancer development on average for 4 years, was associated with a 22-fold increased risk for incident oropharyngeal cancer.

Detection of other oral HPVs (beta1 HPV5, and gamma11 and 12 species) were associated with a 3.3 to 5.5-fold higher risk of  head and neck squamous cell carcinoma after adjustment for smoking, alcohol and HPV16. Associations of beta and gamma HPVs, which have been identified in the skin, with risk of HNSCC suggest a broader role for HPVs in HNSCC etiology.

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HPV Vaccination Rate Low for Girls Under Both Commercial and Medicaid Plans

Shannon Stokley, MPH Epidemiologist in the CDC Immunization Services Division

Shannon Stokley MPH

MedicalResearch.com Interview with:
Shannon Stokley, MPH

Epidemiologist in the
CDC Immunization Services Division

Medical Research: What is the background for this study? What are the main findings?

Response: To determine whether the recommended HPV vaccination series is currently being administered to adolescents with health insurance, CDC and the National Committee for Quality Assurance (NCQA) assessed 2013 data from the Healthcare Effectiveness Data and Information Set (HEDIS). The HEDIS HPV Vaccine for Female Adolescents performance measure evaluates the proportion of female adolescent members in commercial and Medicaid health plans who complete the recommended HPV vaccination series by age 13 years. In 2013, in the United States, the median HPV vaccination coverage level for female adolescents among commercial and Medicaid plans was 12% and 19%, respectively (ranges = 0%–34% for commercial plans, 5%–52% for Medicaid plans). The results of this study indicate that there are significant opportunities for improvement as HPV vaccination coverage among female adolescents was low for both commercial and Medicaid plans.

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Women Who Don’t Get HPV Vaccine May Also Not Get PAP Tests

MedicalResearch.com Interview with:
Ann Goding Sauer
Epidemiologist, American Cancer Society, Inc.
Atlanta, GA 30303

MedicalResearch: What is the background for this study?

Response: Among US women, a positive association between Pap test uptake and HPV vaccination has been shown, though potential variation of the association by race/ethnicity had not been explored previously. The prevalence of some HPV types varies across different racial/ethnic groups so it is important to explore the association between Pap test uptake and HPV vaccination in detail.

MedicalResearch: What are the main findings?

Response: Pap test uptake was significantly lower among those who had not initiated HPV vaccination (81.0%) compared to women who had initiated vaccination (90.5%) (adjusted prevalence ratio = 0.93, 95% CI: 0.90–0.96). This result was seen across most of the sociodemographic factors examined, though not statistically significant for non-Hispanic blacks, Hispanics, those with lower levels of education, or those with higher levels of income.

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Study Tests Two Dose Schedule of HPV Vaccination Against Genital Warts In Girls

Maria Blomberg Virus, Lifestyle & Genes Danish Cancer Society Research Centre Copenhagen, DenmarkMedicalResearch.com Interview with:
Maria Blomberg
Virus, Lifestyle & Genes
Danish Cancer Society Research Centre
Copenhagen, Denmark

Medical Research: What is the background for this study? What are the main findings?

Response: Two vaccines against human papillomavirus (HPV) were licensed almost one decade ago. Since then multiple countries have implemented HPV vaccination programs, but many struggle with low coverage rates.  An important barrier to vaccination is the cost of the vaccines and less developed countries also face considerable logistical challenges. Both vaccines were administered as three dose schedules, but in early 2014 the WHO’s Strategic Advisory Group of Experts and the European Medicines Agency reviewed the evidence of reduced dose schedules of HPV vaccination, and subsequently recommended a two dose schedule for young girls. A reduction of the number of doses has obvious advantages; it would lower the costs, ease implementation of vaccination schedules and potentially increase coverage rates. Based on these recommendations, countries around the world have reduced the dosing schedule in their HPV vaccination programs for young girls to two doses. However, the current evidence is based primarily on immunological studies, and because the immune correlate of protection is not known, studies with disease endpoints are very important.

Using the biologically relevant endpoint of genital warts, this study aimed to assess the clinical effectiveness of a two dose schedule of quadrivalent HPV vaccine compared with the standard three-dose regimen administered at month 0, 2 and 6. We found that with the standard vaccination schedule, completion of the three dose regimen is important to gain maximal protection. However, the effectiveness of two doses increased significantly with increasing time between the doses, and with an interval of approximately 6 months between dose one and two, no differences could be found between two and three doses.

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HPV Vaccination of Boys Can Yield Substantial Health Benefits

MedicalResearch.com Interview with:
Dr. Johannes Berkhof
Department of Epidemiology and Biostatistics, VU University Medical Centre
Amsterdam
Centre for Infectious Disease Control,
National Institute for Public Health and the Environment, Bilthoven, Netherlands

Medical Research: What is the background for this study? What are the main findings?

Response: Vaccination against the sexually transmitted human papillomavirus (HPV) is offered free-of-charge to 12-year-old girls in the Netherlands.
There is strong evidence that HPV also causes cancer in men: the virus is associated with cancers of the penis, anus, and oropharynx, and possibly with a small proportion of oral cancers. A number of these cancers will be prevented because vaccination of girls leads to a decrease of  HPV in the general population and thus provides indirect protection to heterosexual men.

However, vaccine uptake among girls is only about 60 percent in the Netherlands. Moreover, men who have sex with men are at increased risk of HPV-related cancer and will not be protected by vaccination of girls.

On the basis of data from several epidemiological studies and a dynamic model for virus transmission, we calculated that, if the vaccine uptake is low, about 200 girls need to be vaccinated to prevent one case of cervical cancer and 470 boys need to be vaccinated to prevent one case of cancer in men.

An increase in vaccine uptake in girls will decrease the HPV infection risk in heterosexual men and if the uptake in girls is 60 percent, around 800 boys need to be vaccinated to prevent one additional case of cancer in men.

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HPV Vaccine Still Valuable For Women Who Were Not Fully Vaccinated As Children

Jacqueline Hirth, PhD, MPH Assistant Professor andMedicalResearch.com Interview with:
Jacqueline Hirth, PhD, MPH
Assistant Professor and
Dr. Abbey B. Berenson MD, MMS, PhD Center for Interdisciplinary Research in Women's Health Obstetrics and Gynecology The University of Texas Medical Branch at Galveston TexasDr. Abbey B. Berenson MD, MMS, PhD
Center for Interdisciplinary Research in Women’s Health
Obstetrics and Gynecology
The University of Texas Medical Branch at Galveston Texas

Medical Research: What is the background for this study? What are the main findings?

Response: In this sample of young women, vaccination was effective at reducing prevalence of vaccine-type HPV (6,11,16,18) compared to women who were unvaccinated. We also found a dose response, with young women who received at least 2 doses of the 3 dose vaccine series having a lower rate of vaccine-type HPV compared to those who only received one dose (8.6% compared to 16.9%, respectively).

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HPV Vaccine Provides Protection at Multiple Sites

Daniel C. Beachler, PhD, Postdoctoral fellow Infections and Immunoepidemiology Branch of the National Cancer Institute (NCI) MedicalResearch.com Interview with:
Daniel C. Beachler, PhD
Postdoctoral fellow
Infections and Immunoepidemiology Branch of the
National Cancer Institute (NCI)

Medical Research: What is the background for this study? What are the main findings?

Dr. Beachler: HPV is a common sexually transmitted infection. Individuals can acquire HPV infections in the epithelium of their cervical, anal and oral sites, and occasionally these infections lead to cancer. There are three prophylactic HPV vaccines on the market that can protect against HPV at these sites among those not been previously exposed to HPV.
This study examined the effect of HPV vaccination of 18-25 year old women at all three anatomic sites. The combined multi-site HPV vaccine efficacy has not been reported previously. It was unknown whether the vaccine may protect non-infected sites against HPV infection or re-infection in women exposed to HPV prior to vaccination.
We observed that the HPV vaccine provides the strongest protection at all three sites among women unexposed to HPV before vaccination. Additionally, we observed some protection at the non-infected sites in women who were previously infected with HPV.

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New Antiviral Medication For HPV Infection Shows Promise

MedicalResearch.com Interview with:
Luis Squiquera, MD

Tamir Biotechnology

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Squiquera: Ranpirnase is a small peptide that has a characteristic enzymatic activity against double stranded RNA (dsRNA). As a drug it has been extensively tested intravenously in high concentration for oncology in over 1000 patients with different types of malignancy, especially mesothelioma, with minimal side effects and mainly a transient increase of serum creatinine level observed.

In the last year we started a comprehensive antiviral program and obtained encouraging results in several RNA and DNA virus families. Several research groups have already studied the anti HIV activity. HPV was one of many viruses that showed a high selectivity index in our antiviral screening (the relationship between efficacy and cytotoxicity). We were encouraged by the low concentrations (nanomolar range) needed to stop virus reproduction in cell cultures. We performed in vitro analysis of two of the main HPV types that cause human disease (HPV 11 and 16). HPV 11 was highly sensitive to ranpirnase; and since this is one of the main virus type responsible for inducing genital warts, we decided to focus our efforts in bringing the drug to a new route of administration.

We set out to obtain and did obtain a formulation that was extremely stable, even at high temperatures. Before using it in patients, we performed testing for irritation using standardized Draize animal models. Even though we ran these tests in high concentrations (1 mg/ml) the final product was not irritant and was deemed safe to use in a clinical setting.

With these safety data on hand – plus extensive experience in IV dosing and non-irritation in animal models – we decided to make the formulation available as a compassionate use for patients with genital warts.

As we reported in our presentation in San Francisco, all cases that completed an 8-week treatment showed clearance of the lesions. Some of the cases were cleared in as soon as two weeks and the average time for clearance was 33 days. One of the patients had to be discontinued due to an eczematous skin reaction. We will be studying the characteristic of this effect in our trials. Continue reading

Random Stem Cell Divisions May Play Role in Persistent HPV Infections

Marc Ryser PhD Visiting Assistant Professor Department of Mathematics Duke University Durham, North CarolinaMedicalResearch.com Interview with:
Marc Ryser PhD
Visiting Assistant Professor Department of Mathematics
Duke University Durham, North Carolina

Medical Research: What is the background for this study

Dr. Ryser: Infection with the human papillomavirus (HPV) is responsible for approximately 5% of all cancers worldwide. In addition to cervical cancers, HPV is associated with various other female and male cancers, including cancers of the anus and oropharynx. Despite expansive screening and vaccination programs, HPV-related cancers remain a serious public health concern in the US and abroad. To further improve public health interventions against HPV, a thorough understanding of the underlying biology is critical.

The lifetime risk of getting infected with HPV is as high as 80%, yet most individuals remain asymptomatic and clear the virus after 1-2 years.  However, if an infection with a high-risk type of HPV persists, the virus can interfere with the replication mechanism of the host cells, and initiate tumor growth. Even though our understanding is incomplete to date, clearance of HPV infections is primarily attributed to an effective immune response.

Interestingly, recent studies about the stem cell dynamics in epithelial tissues – the types of tissues that are affected by HPV –  have shown that the fate of these stem cells is random: most of the time, a stem cell divides into a new stem cell and a differentiating daughter cell; however, every now and then, a stem cell divides either into two stem cells, or into two differentiating daughter cells. These dynamics have not been acknowledged by the HPV community, and our goal was to develop mathematical models to examine whether the random division patterns of stem cells could play a role in the clearance of HPV infections.
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