Health Report:

Human Papilloma Virus (HPV), Pap Smear Results & Cervical Cancer

Human Papilloma Virus (HPV) Infection & Oral Cancer

Hormone Replacement Therapy (HRT) & the Risk of Gastroesophageal Reflux Disorder (GERD)

"A critical weekly review of important new research findings for health-conscious readers..."

By, Robert A. Wascher, MD, FACS

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Last Updated: 4/6/2008

The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author.  Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.


An estimated 11,000 women will be diagnosed with cancer of the cervix in the United States in 2008, and almost 4,000 will die of the disease.  The majority of cervical cancer cases, by far, are thought to result from chronic infection with certain strains of human papilloma virus (HPV) that are known to induce cancer.  These high-risk strains of HPV are commonly spread though sexual contact and, increasingly, these oncogenic HPV strains are being linked to a variety of cancers in both men and women (see next article, below).  Recently, the FDA has approved a new vaccine against HPV (Gardasil®), and other vaccines against HPV are in the pipeline as well.  However, once a woman (or man) becomes infected with HPV, the vaccine is no longer effective or helpful.

For most women, annual screening for cervical cancer includes a “Pap smear,” named after Dr. Georgios N. Papanikolaou, the Greek-American physician who originally developed the test.  During a woman’s routine annual pelvic examination, a thin layer of superficial cells are scraped off of the cervix and examined under the microscope.  In a few hospitals, the cells are also routinely tested for the presence of oncogenic HPV infection.  However, in most hospitals, if the cervical cells appear normal under the microscope, then the costly DNA testing for oncogenic HPV infection is omitted.  A new study, just reported in the current issue of the Annals of Internal Medicine, evaluated nearly 10,000 women at 26 clinical facilities, in 6 cities, in the United States by including DNA testing for oncogenic HPV infections of the cervix in addition to performing a Pap smear.  The results of the DNA tests for HPV infection were then correlated with the findings of the Pap smear tests.

Overall, nearly 1 in 4 (23%) of the women participating in this trial had DNA evidence of chronic infection of the cervix with one or more high-risk strains of the HPV.  Women 14 to 19 years of age were most commonly found to be infected with these strains of HPV, while women 50 and older were least likely to be infected.  Among women younger than 30 years of age with an abnormal Pap smear, a whopping 53% had DNA evidence of chronic cervical infection with oncogenic HPV strains, while 9% of women 30 years of age and older who had a normal Pap smear had DNA evidence of high-risk HPV infection.

The findings of this study have several important implications, the two most important of which are improving prevention of cervical cancer, and improving screening for this disease.  With the recent availability of a vaccine that appears to be more than 90% protective against cervical HPV infection in women, there is finally an effective method of preventing infection with the oncogenic strains of the HPV virus (of course, taking appropriate measures to avoid unprotected sexual contact should always be used, when appropriate). 

Secondly, the results of this test show that even among women who are already above the age range considered to be at greatest risk of infection with high risk HPV and who have a normal Pap smear, nearly 1 in 10 are already likely to be infected with cancer-causing strains of HPV.   This finding strongly suggests that Pap smears alone are missing a significant number of cases of chronic oncogenic HPV infection.  Based upon the results of this study, it may be the case that we will have to reassess our current screening guidelines for cervical cancer.



The vast majority of oral cancers are diagnosed in patients (and mostly men) who are heavy drinkers and smokers.  However, approximately 20% of oral cancers diagnosed today occur in patients who have never smoked.  HPV, a family of viruses that are easily passed between people during sexual contact, has previously been implicated in these particular cases of oral cancer (the same oncogenic strains of HPV that are known to cause cervical cancer also appear to cause oral cancer as well).  A new study in the journal Carcinogenesis provides important further insight into the association of HPV with oral cancer, especially among non-smokers. 

In this study, 186 patients newly diagnosed with squamous cell cancer of the oropharynx and 342 cancer-free “control” patients were compared.  All patients participating in this study underwent a blood test for the HPV strain most commonly associated with both cervical and oral cancers (HPV-16).  Overall, having a positive blood test for HPV-16 was almost 6 times more common among the patients diagnosed with oral cavity cancers.  When the researchers looked at just the non-smokers in both groups of patients, the association between HPV-16 and oral cancer was even more striking: oral cancer was a whopping 14 times more frequent among the non-smoking patients in presence of HPV-16 infection. 

An additional part of this research study looked at variations in a very important cancer suppressor gene, p53.  Patients with a specific variation (polymorphism) in the p53 gene and with evidence of HPV-16 infection were 9 times more likely to have oral cancer.  However, among non-smoking patients with evidence of HPV-16 infection and the “codon 72 polymorphism” in the p53 gene, there was a nearly 23-fold increase in the likelihood of having oral cancer, which is an incredibly high level of increased risk for any disease. 

The results of this study confirm other recent data suggesting that oncogenic strains of HPV are significantly involved in causing many cases of oral cancers, especially in non-smokers; and that certain naturally occurring variations in important tumor suppressor genes may further magnify the risk of developing this cancer in the presence of chronic HPV infection.  The findings of this study, and others like it, have also added further weight to the argument that boys and young men should also be considered for vaccination against HPV, rather than the current guidelines which recommend its use for girls and young women, only.



Gastroesophageal reflux disorder (GERD) has been linked to the increasing prevalence of a high-fat diet among people in westernized societies, and especially to the rising incidence of obesity throughout the world.  In addition to the symptoms of chronic heartburn that often (but not always) accompany GERD, severe GERD has been linked to chronic scarring of the esophagus, and to an increased risk of esophageal cancer, a particularly deadly form of cancer.  Pregnancy is another risk factor that has long thought to increase the risk of GERD, due to a combination of increased levels of female hormones known to cause relaxation of the sphincter muscle in the lower esophagus (and that prevents reflux of acid up from the stomach), and increased pressure within the abdomen of pregnant women, which also increases the tendency for acid to percolate up from the stomach and into the esophagus.

A new study in the journal Gastroenterology has evaluated the role of female hormones, in the form of hormone replacement therapy (HRT) following menopause, and oral contraceptives, in the development of GERD.  In this Swedish study, a registry of twins was utilized to collect data on 4,365 women with known GERD and 17,321 women without GERD.  A history regarding prior use of oral contraceptive pills (OCPs) and various forms of HRT was obtained through telephones interviews and questionnaires. 

Among the women who previously or currently used estrogen-only HRT, there was a 32% increase in the risk of having GERD when compared to women who had never used HRT or OCPs.  However, the prior or current use of OCPs did not appear to be linked to an increased risk of GERD. 

While, as I have previously commented upon, survey- or questionnaire-based epidemiological studies have great potential to be biased on the part of those asking the questions, and by those answering them, this study does at least suggest the possibility that estrogen-only HRT medications may be associated with an increased risk of GERD.  However, there is a large randomized, prospective, double-blinded HRT study, the landmark Women’s Health Initiative (WHI) study, that should be able to definitively corroborate or contradict this Swedish epidemiological study’s findings.  I look forward to that analysis of the WHI study’s enormous collection of data in the near future.


Disclaimer:  As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity.

Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center


Send your feedback to Dr. Wascher at rwascher@doctorwascher.net

Links to Other Health & Wellness Sites

Copyright 2008.  Robert A. Wascher, MD, FACS.  All rights reserved.

Dr. Wascher's Archives:

3-30-2008:  Abdominal Obesity & the Risk of Death in Women; Folic Acid Pretreatment & Heart Attacks; Pancreatic Cancer Regression after Injections of Bacteria

3-23-2008:  Age of Transfused Blood & Risk of Complications after Surgery; Obesity, Blood Pressure & Heart Size in Children

3-16-2008:  Benefits of a Full Drug Coverage Plan for Medicare Patients?; Parent-Teen Conversations about Sex; Soy (Genistein) & Prostate Cancer

3-9-2008:  Flat Colorectal Adenomas & Cancer; Health Risks after Stopping Hormone Replacement Therapy (HRT); Television, Children & Obesity 

3-2-2008:  Medication & Risk of Death After Heart Attack; Hormone Replacement Therapy (HRT) & Mammogram Results; Selenium: Cancer, Heart Disease & Death

2-23-2008:  Universal Healthcare Insurance Study; Glucosamine & Arthritis

2-17-2008:  Exceptional Longevity in Men; Testosterone & Risk of Prostate Cancer; Smoking & Pre-malignant Colorectal Polyps

2-10-08:  Thrombus Aspiration from Coronary Arteries; Intensive Management of Diabetes & Death; Possible Cure for  Down's Syndrome?

2-3-2008:  Vitamin D & Cardiovascular Health; Vitamin D & Breast Cancer; Green Tea & Colorectal Cancer

1-27-2008:  Colorectal Cancer, Esophageal Cancer & Pancreatic Cancer: Update from the 2008 American Society of Clinical Oncology's Gastrointestinal Cancers Symposium

1-20-2008:  Testosterone Levels & Risk of Fractures in Elderly Men; Air Pollution & DNA Damage in Sperm; Statins & Trauma Survival in the Elderly

1-12-2008:  Statins, Diabetes & Stroke and Obesity; GERD & Esophageal Cancer

1-7-2008:  Testosterone Supplements in Elderly Men; Colorectal Cancer-- Reasons for Poor Compliance with Screening Recommendations

12-31-2007:  Minority Women, Hormone Replacement Therapy & Breast Cancer; Does Health Insurance Improve Health?

12-23-2007:  Is Coffee Safe After a Heart Attack?; Impact of Divorce on the Environment; Hypertension & the Risk of Dementia; Emotional Vitality & the Risk of Heart Disease

12-16-2007:   Honey vs. Dextromethorphan vs. No Treatment for Kids with Night-Time Cough, Acupuncture & Hot Flashes in Women with Breast Cancer, Physical Activity & the Risk of Death, Mediterranean Diet & Mortality 

12-11-2007:  Bias in Medical Research; Carbon Nanotubes & Radiofrequency: A New Weapon Against Cancer?; Childhood Obesity & Risk of Adult Heart Disease

12-2-2007:  Obesity & Risk of Cancer; Testosterone Level & Risk of Death; Drug Company Funding of Research & Results; Smoking & the Risk of Colon & Rectal Cancer 


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