Cervical Cancer Subtypes Vary Among Population Sectors

MedicalResearch.com Interview with:

Farhad Islami, MD PhD Scientific Director, Surveillance Research American Cancer Society, Inc. Atlanta, GA 30303

Dr. Islami

Farhad Islami, MD PhD
Scientific Director, Surveillance Research
American Cancer Society, Inc.
Atlanta, GA 30303 

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

Response: Despite a continuous decline in cervical cancer incidence rates, earlier studies reported an increase in cervical adenocarcinoma incidence rates. However, those reports had major limitations, as they did not account for changes in hysterectomy prevalence and used cancer occurrence data covering only 10%-12% of the U.S. population (which may not be representative of the entire population, especially racial/ethnic minorities).

Further, the most recent study examined the trends by age and histology through 2010. We examined contemporary trends in cervical cancer incidence rates in the U.S. (1999-2015) by age, race/ethnicity, major histological subtypes, and stage at diagnosis using up-to-date nationwide data after accounting for hysterectomy prevalence.

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Massive Reduction in Cervical Cancer Among Vaccinated Young Women

MedicalResearch.com Interview with:

Dr. Tim PalmerHonorary Senior LecturerDepartment of PathologyUniversity of EdinburghEdinburgh, UK

Dr. Palmer

Dr. Tim Palmer
Honorary Senior Lecturer
Department of Pathology
University of Edinburgh
Edinburgh, UK 

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

Response: High risk HPV infection is the obligate cause of between 70 and 90% of cervical cancers, depending upon the country. The development of vaccines against the commonest hr-HPV types has the potential to reduce the burden of cervical cancer, especially in low and middle income countries that cannot afford screening programmes. Cervical cancer affects predominantly women in their 30s and is a major public health issue even in countries with well-established screening programmes. Scotland has had a successful immunisation programme since 2008, and women immunised at age 12 to13 have been screened since 2015. We can therefore demonstrate the effect of hr-HPV immunisation on the pre-invasive stages of cervical cancer.

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Therapeutic HPV Vaccine Can Trigger Resolution of Virus and Cervical Cancer in Some CIN Patients

MedicalResearch.com Interview with:

Diane Harper, M.D., M.P.H., M.S.Professor of Family Medicine and Obstetrics and GynecologySenior Associate Director, Michigan Institute for Clinical and Health ResearchPhysician Director for Community Outreach, Engagement and Health Disparities,Rogel Cancer CenterMichigan Medicine

Dr. Harper

Diane Harper, M.D., M.P.H., M.S.
Professor of Family Medicine and Obstetrics and Gynecology
Senior Associate Director, Michigan Institute for Clinical and Health Research
Physician Director for Community Outreach, Engagement and Health Disparities,
Rogel Cancer Center
Michigan Medicine 

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

Response: There is no current cure for women with HPV infection that has progressed to CIN 2/3 disease. The only treatment is for the diseased cervix, and does not eliminate the risk of another CIN 2/3 from the HPV infection 15-20 years later.

This vaccine is made from a live virus that has 3 genes inserted:  human cytokine IL-2, and modified forms of HPV 16 E6 and E7 proteins. When the vaccine is injected subcutaneously, the proteins for HPV 16/E6 and E7 and the cytokine LI-2 proteins are made. These proteins trigger the immune response.  This is very different form imiquimod which is topical and not specific for HPV.

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HPV Testing for Primary Cervical Cancer Screening

MedicalResearch.com Interview with:

Matejka Rebolj, PhD King’s College London, London, UK

Dr. Rebolj

Matejka Rebolj, PhD
King’s College London, London, UK

Henry Kitchener, MD FRCOG FRCS University of Manchester, Manchester, UK

Dr. Kitchener

 

Professor Henry Kitchener, MD FRCOG FRCS
University of Manchester, Manchester, UK

 

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

Response: We now have reliable and affordable technologies to detect human papillomavirus (HPV), a virus which is universally accepted as the cause of cervical cancer. Various large trials confirmed that cervical screening could be improved by replacing the smear (cytology) test that has been in use for decades, with HPV testing. Many countries are now making the switch. In England, this is planned for the end of 2019. To test how to run HPV testing within the English National Health Service, a pilot was initiated in 2013 in six screening laboratories. We also wanted to determine whether the encouraging findings from the trials could be translated to everyday practice. This is important not only because we will be using different HPV tests, but also because women undergoing screening in trials are much more selected than those who are invited to population-based screening.  Continue reading

Self Sampling for Cervical HPV: Useful Screening Tool

MedicalResearch.com Interview with:

Prof. J. (Hans) Berkhof PhD Vrije Universiteit Amsterdam 

Prof. Berkhof

Prof. J. (Hans) Berkhof PhD
Vrije Universiteit
Amsterdam 

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

Response: In most countries, the Pap test is used for cervical cancer screening but recently several countries have switched from Pap testing to HPV testing.

Like the Pap test, the HPV test requires a cervical sample to be taken by a clinician. Vaginal self-sampling is also used, but only in underscreened women. We know that self-sampling increases screening participation in underscreened women and it is likely that many women that attend screening also prefer self-sampling if it had been offered to them.

We studied whether an HPV self-sampling test is an accurate alternative to a regular HPV test in women invited for routine screening. We randomized about 14,000 women, invited for screening, to self-sampling or clinician-sampling. Women with a positive HPV test result also received the other HPV test.

We found that the HPV self-sampling test yielded similar performance as the regular HPV test for detection of cervical pre-cancerous lesions (CIN3 and CIN2).  Continue reading

Why Aren’t More Teens Vaccinated Against Cancer Causing HPV?

MedicalResearch.com Interview with:

Anna Beavis, MD, MPH Assistant Professor The Kelly Gynecologic Oncology Service Department of Gynecology and Obstetrics Johns Hopkins Medicine Baltimore, MD 21287-128

Dr. Beavis

Anna Beavis, MD, MPH
Assistant Professor
The Kelly Gynecologic Oncology Service
Department of Gynecology and Obstetrics
Johns Hopkins Medicine
Baltimore, MD 21287-128

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

Response: We wanted to look at reasons parents don’t vaccinate their children against HPV, including how those reasons have changed over time from 2010-2016 and how those reasons are different between boys and girls in the most recent data from 2016. We used a nationwide dataset which is publically available from the CDC (Centers for Disease Control) – the National Immunization Survey-Teen, or NIS-Teen – which surveys parents of teens ages 13-17 years old every year to determine rates of all recommended vaccinations. In parents who report that they don’t intend to vaccinate their child against HPV , the survey asks parents why.

We found that from 2010 to 2016, the percentage of parents reporting concerns about their child not being sexually active yet went down significantly for both boys and girls. Also, in boys specifically, parents reported male gender as a less common reason for not vaccinating. For both boys and girls, we found that concerns about safety and side effects, necessity, and lack of knowledge about the vaccine were common reasons for not planning to vaccinate.  Also, 10% of parents of girls vs. 20% of parents of boys reporting never having a provider recommendation for the vaccine as their primary reason for not vaccinating.

These results may reflect the growing public understanding of the HPV vaccine as a vaccine which is best given before exposure, so before initiation of sexual activity between the ages of 11 and 12, and that it is recommended for both boys and girls. Also, over 80% of people will have an HPV infection in their lifetime, so everyone should get vaccinated regardless of anticipated sexual activity.

Additionally, providers should focus their counseling and recommendation on improving knowledge about the HPV vaccine, including its decade-long track record of safety and necessity.    Continue reading

HPV Testing or PAP Smear To Screen for Cervical Cancer?

MedicalResearch.com Interview with:

Joy Melnikow, MD, MPH Professor, Department of Family and Community Medicine Director, Center for Healthcare Policy and Research University of California, Davis Sacramento, CA 95817

Dr. Melnikow

Joy Melnikow, MD, MPH
Professor, Department of Family and Community Medicine
Director, Center for Healthcare Policy and Research
University of California, Davis
Sacramento, CA 95817

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

Response: This systematic review of the medical literature was conducted to support the update of the US Preventive Services Task Force Recommendation.  Because the effectiveness of cytology (Pap smear) screening is so well established, the review focused on the evidence on use of high risk Human Papillomavirus (hrHPV) screening, alone (primary screening) or combined with cytology (co-testing)

MedicalResearch.com: What should readers take away from your report?

Response: Current evidence supports the use of cytology, hrHPV testing alone, or co-testing as effective approaches to screening for cervical cancer.  hrHPV testing, alone or as co-testing, can be done at five year intervals, longer than the recommended 3 year interval for cytology. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: Additional research is needed to identify effective strategies for outreach and screening women who are not regularly screened.  Because most women in the US are not part of an organized screening program, effective outreach is especially important in the US. 

MedicalResearch.com: Is there anything else you would like to add?

Response: Since the prior review, more evidence has emerged to support the use of hrHPV testing as primary screening.

I have no financial conflicts of interest. 

Citation:

US Preventive Services Task Force. Screening for Cervical CancerUS Preventive Services Task Force Recommendation Statement. JAMA. 2018;320(7):674–686. doi:10.1001/jama.2018.10897

Aug 22, 2018 @ 12:01 pm 

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Cervical Cancer Is Not Just a Young Woman’s Disease: Older Women Should Have PAP Smears Too

MedicalResearch.com Interview with:

Mary C. White, ScD Epidemiology and Applied Research Branch Division of Cancer Prevention and Control, CDC Atlanta GA 30341

Dr. Mary White

Mary C. White, ScD
Epidemiology and Applied Research Branch
Division of Cancer Prevention and Control, CDC
Atlanta GA 30341

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

Response: For women between the ages of 21 to 65, Pap testing every three years, or Pap testing with HPV co-testing every five years, can prevent cervical cancers and deaths.

Current recommendations state that women 65 and older and not otherwise at special risk can skip Pap tests, but only if they have had three consecutive negative Pap screening tests or two consecutive negative co-tests over the past 10 years, with the most recent done within the past five years.

We used data from two federal cancer registry programs to examine how cervical cancer risk changes with age, after excluding women who have had a hysterectomy. We also examined data from a federal national health survey to examine the proportion of women who either had never been tested or had not been tested in the last 5 years.

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Epigenetic Biomarker May Improve Cervical Cancer Screening

Christos Nikolaidis Ph.D. Laboratory of Pharmacology Medical School, Democritus University of Thrace Dragana, Alexandroupolis GreeceMedicalResearch.com Interview with:
Christos Nikolaidis Ph.D.
Laboratory of Pharmacology
Medical School, Democritus University of Thrace
Dragana, Alexandroupolis Greece

Medical Research: What is the background for this study?

Response: Epigenetic changes are part of the natural history of cervical neoplasia. Tracking these changes at the molecular level is necessary for understanding disease progression, response to treatment and prognosis. Epigenetic biomarkers can potentially assess the stage of cervical intraepithelial neoplasia (CIN). This information can be used for screening purposes, to improve the overall quality of cervical cancer diagnostics.

Medical Research: What are the main findings?

Response: Paired boxed 1 (PAX1) gene methylation status has been widely used as a biomarker for cervical cancer screening.  We have conducted a meta-analysis of the diagnostic test accuracy of PAX1 methylation, on moderate cervical dysplasia or worse (CIN2+) versus normal epithelium, and severe cervical dysplasia or worse (CIN3+) versus normal epithelium, for a total population of 1385 women. The results of this assay were generally satisfactory for CIN2+ vs normal, and extremely satisfactory for CIN3+ vs normal (Sensitivity=0.77, Specificity=0.92, AUC=0.931). This raises the possibility of utilizing this biomarker to improve current diagnostic protocols.

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Strong Evidence HPV Vaccination Highly Effective Outside Trial Settings

MedicalResearch.com Interview with: Marc Brisson Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease Associate Professor, Université LavalMedicalResearch.com Interview with:
Marc Brisson

Canada Research Chair in Mathematical Modeling and Health Economics of Infectious Disease
Associate Professor, Université Laval

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

Response: Since 2007, 52 countries have implemented human papillomavirus vaccination (HPV) programmes. Two HPV vaccines are currently available worldwide: the bivalent vaccine, which targets HPV types 16 and 18, causing 70-80% of cervical cancer, and the quadrivalent vaccine, which also targets HPV types 6 and 11, associated with 85-95% of anogenital wart cases. Large international randomised controlled clinical trials have shown both vaccines to be safe, well tolerated and highly efficacious against vaccine-type persistent infections and precancerous cervical lesions.  Furthermore, both vaccines have shown some level of cross-protection against 3 HPV types (HPV 31, 33 and 45) not included in the vaccine and associated with a supplementary 10-15% of cervical cancers worldwide. Now that 7 years have elapsed since the implementation of the first HPV vaccination program, we verified whether the promising results from clinical trials are materialising at the population level. We conducted a meta-analysis to examine the population-level impact in countries that have introduced HPV vaccination programs.

In countries with high female vaccination coverage (<50%), our main findings indicate:

  • sharp declines in HPV-related outcomes among females targeted for vaccination (e.g., HPV-16/18 infection and anogenital warts declined by more than 60% in females younger than 20 years), and
  • evidence of cross-protection with significant reductions in HPV-31/33/45 infection among females younger than 20 years
  • evidence of herd effects (indirect benefit of vaccination among unvaccinated individuals) with significant reductions in anogenital warts among males and older females.

In countries with low coverage (<50%), we report:

  • significant reductions in HPV-16/18 infection and anogenital warts among young females, with no indication of herd effects or cross-protection. Continue reading

HPV-16/18 Vaccine Provides Some Cross Protection To Other Cancer-Causing Subtypes

MedicalResearch.com Interview Invitation
Frank Struyf MD PhD
Director, Lead Clinical Development HPV vaccines at GlaxoSmithKline Biologicals GlaxoSmithKline Vaccines,
Rixensart, Belgium

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

Dr. Struyf: Cervical cancer is the fourth most common cancer among women, with estimates from 2012 indicating that there are 528,000 new cases and 266,000 deaths each year worldwide, the majority of cases occurring in developing countries (reference: Globocan 2012 at http://globocan.iarc.fr/old/FactSheets/cancers/cervix-new.asp). Persistent infection with oncogenic human papillomavirus (HPV) is a necessary condition for the development of invasive cervical cancer. HPV type 16 (HPV-16) and HPV-18 are found in approximately 70% of cases. We conducted the Papilloma Trial Against Cancer in Young Adults (PATRICIA), a multinational clinical trial in 14 countries in Europe, the Asia-Pacific region, North America, and Latin America and enrolled over 18,000 women. The trial showed that the HPV-16/18 AS04-adjuvanted vaccine not only prevented persistent infections and high-grade cervical lesions associated with HPV types 16 and/or 18 included in the vaccine, but also protected against some common related oncogenic HPV types not included in the vaccine. However, during the analysis of this trial, we also noticed that for some rare nonvaccine oncogenic HPV types, the vaccine efficacy against infections did not seem to match the efficacy against lesions associated with the same HPV type. To investigate this, we re-analyzed the samples from the trial using a different PCR method and found that the HPV PCR methodology used per protocol may have underestimated the efficacy for non-vaccine HPV types in cases of multiple infections. While these results do not replace the results generated according to the study protocol and included in the product label, they are reassuring, as they confirm the cross-protective efficacy of the HPV-16/18 vaccine against some HPV types related to those included in the vaccine.
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New Ninevalent HPV Vaccine Gives Greater Protection Against Cervical Cancer and Genital Warts

Elmar A. Joura, M.D Gynecologist University of ViennaMedicalResearch.com Interview with:
Elmar A. Joura, M.D
Gynecologist
University of Vienna

MedicalResearch: What are the main findings of this study?

Dr. Joura: This study demonstrates that the new ninevalent HPV vaccine induces a good immunogenicity against HPV 6/11/16/18 and gives a 97% protection against disease caused by HPV 31/33/45/52/58. This has a potential of a 90% reduction of cervical cancer and other HPV related cancers and a similar protection against genital warts. The full benefit is seen in persons without current HPV infection, this reinforces early vaccination against HPV. The safety profile was favourable.
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Treating Metastatic Cervical Cancer With HPV-Targeted TILs

Dr. Christian S Hinrichs MD Assistant Clinical Investigator Center for Cancer Research National Cancer Institute Bethesda, MD 20814MedicalResearch.com Interview with:
Dr. Christian S Hinrichs MD
Assistant Clinical Investigator
Center for Cancer Research
National Cancer Institute
Bethesda, MD 20814

MedicalResearch: What are the main findings of the study?

Dr. Hinrichs: Objective tumor regression occurred in 3/9 patients with metastatic cervical cancer. Two responses were complete and are ongoing 22 and 15 months after treatment with a single infusion of T cells targeting the HPV oncoproteins.
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HPV Vaccination and Prevention of Cervical Abnormalities

MedicalResearch.com Interview with:
Dr Julia Brotherton
Victorian Cytology Service, Melbourne, Victoria, Australia

Dr Elizabeth Crowe
The University of Queensland, School of Population Health, Brisbane, Australia
NHS Borders, Department of Public Health, Melrose, Scotland, UK

Prof. David Whiteman
Group Leader / Department Coordinator
QIMR Berghofer Medical Research Institute
Royal Brisbane Hospital, QLD 4029

MedicalResearch.com: What are the main findings of the study?

1.       We conducted a case-control study in which we retrieved the HPV vaccination histories of young Australian women who were notified to the Pap smear registry with high-grade cervical lesions or with other types of cervical lesions, and compared them with the vaccination histories of women whose Pap smears showed only normal cytology.

2.       We found that women with high grade cervical lesions were significantly less likely than women with normal cytology to have received 3 doses of the quadrivalent HPV vaccine, equivalent to a vaccine effectiveness of 46%.

3.       The vaccine effectiveness among 15-19 year old women was even higher at 57%. We believe this reflects the fact that HPV16 causes an even higher proportion of high grade disease in young women due to its higher oncogenicity and shorter latent period.

4.       The HPV vaccine had 34% effectiveness against other cervical lesions (i.e. those not proven to be high grade lesions on histology).

5.       We also observed that 2 doses of the vaccine were 21% effective in preventing both high grade lesions and other grade lesions.
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Advanced Cervical Cancer: Adding Avastin to Chemotherapy Prolonged Survival

Krishnansu S. Tewari, MD, FACOG, FACS| Professor & Director of Research Principal Investigator - The Gynecologic Oncology Group at UC Irvine The Division of Gynecologic Oncology University of California, Irvine Medical Center Orange, CA 92868MedicalResearch.com Interview with:
Krishnansu S. Tewari, MD, FACOG, FACS| Professor & Director of Research
Principal Investigator – The Gynecologic Oncology Group at UC Irvine, Division of Gynecologic Oncology
University of California, Irvine Medical Center
Orange, CA 92868

MedicalResearch.com: What are the main findings of the study?

Dr. Tewari: The main findings of this study were that the addition of bevacizumab to chemotherapy resulted in a significantly improved survival of 3.7 months in a population of patients that have very limited options. This improvement in overall survival was not accompanied by any significant deterioration in quality of life and serious side effects were limited to 3% to 8% of the study population.
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