I keep a mental dietary list which I review at the end of each day…”Let’s see, I had juice in the morning, salad at lunch, two vegetables at dinner and fruit for dessert. OK, now I’ve had my five or more fruits and vegetables and have done my nutritional duty to ward off cancer.” It turns out I am giving myself inadequately proven anti-cancer food advice.

The largest prospective study to date, the European Prospective Investigation into Cancer and Nutrition study (wisely acronymed the EPIC study), followed 478,478 individuals aged 25 to 70 years in 10 European countries for a median of 8.7 years. (How they got to a number that has those matching numerals is a mystery.) Unlike many large studies, women comprised the predominant gender (335,873 women vs. 142,605 men). The overall cancer incidence rates were 7.9 per 1000 person –years for men and 7.1 per thousand-person years for women. When the researchers analyzed the impact of daily veggies, they found that an increase of 100 grams (the equivalent of a serving of broccoli) reduced cancer risk by only 2% while a comparable intake of fruit (less than an apple) reduced cancer risk by just 1%. These were very low percentages…and were restricted to women; they didn’t even apply to men who gained no cancer protection.

I would like to remind you of a previous website article in which I cited articles that discourage women from drinking more than 10 grams (one drink) at any time. Well, the researchers that reviewed the EPIC data found that intake of fruit and vegetables did decrease cancer risk by 10% in heavy drinkers (more than 30 g daily for women and 60 grams for men). But considering all the damage that excessive alcohol consumption does to our health, proclaiming that the right foods will prevent certain cancers is not appropriate medical advice.

The American Cancer Society (ACS) still advises that we consume 5 servings of a variety of fruits and vegetables on a daily basis to help reduce cancer risk both directly as well as indirectly by helping maintain a healthy weight. In 2005, ACS made “the 5 rule” the third priority after healthy weight maintenance throughout life and adoption of a physically active lifestyle. The ACS meets to update its recommendations later this summer and will probably change them based on the EPIC study.

But before I encourage you to stop that “5-a-day” nutritional count let’s remember that cardiovascular disease is the number one cause of mortality in women (not cancer). There are many prospective studies that have shown that 5 servings of fruit and vegetables a day reduce cardiovascular risk by as much as 12%.  These foods contain nutrients and vitamins that are essential for all of our bodies’ functions. They most certainly help us maintain a healthy weight and a lower weight  (or more precisely, lack of obesity) will diminish our risk of diabetes, heart disease and many cancers. We have to eat something, and substitutions for fruits and/or veggies usually carry excess calories, sugar, salt and bad fats. (Think processed or junk food.)

I may stop computing those servings in the hope that I will reduce my risk of cancer, but I’ll keep up the count to maintain my heart, weight and future health and well being.

By now most of you have probably heard that ACOG (The American College of Obstetricians and Gynecologists) has made new recommendations as to how often and when to start doing Pap smears. Despite the timing, I don’t feel these are either economically or politically inspired by the currently debate on health care reform. The reasons behind these new recommendations are scientifically sound. I would like to share some of them with you…

It’s extremely difficult for women to reconsider their Pap priorities; after all we have been told for decades that we must have a yearly Pap smear. Indeed we were lead to believe that the Pap was the foremost reason to visit our gynecologist. (When I went to work in Israel after finishing my residency in the US, I tried to explain the importance of Pap smears. My colleagues and residents were puzzled…they had seen very few cases of cervical cancer and thought it only occurred in women with uncircumcised partners…. I’m not sure why it was uncommon, perhaps at the time the population was more monogamous. But a sexually active circumcised penis can spread the viruses that lead to cervical cancer as well as one that is “uncut”. Today Israeli gynecologists routinely do Pap smears. If you continue to read below however, you will see that “routine” has changed for everyone.) But I digress…

Many women believe that the Pap smear can, in its mythological and histological wonder, pick up every type of cancer “down there” including endometrial and ovarian cancer. Unfortunately, it usually won’t. The Pap can detect cells that herald the presence of cervical precancer and cancer caused by sexually transmitted HPV (human papilloma) viruses. There are more than 100 types of these ubiquitous HPV’s. They are all very contagious and easily transmitted during sexual intercourse. At least eighteen of them are deemed high risk. The high risk HPV’s are oncogenic agents which, if not cleared by the immune system, can enter the DNA and cause mutations in the cells of the cervix. These mutations can lead to the development of a precancerous lesion termed high grade squamous intraepithelial lesion or HSL and in turn this can go on to become invasive cancer.

Although an astounding proportion of young women (50 to 70%) are found to have HPV present in their cervix within 2 to 3 years of onset of intercourse, the majority have an immune response that is strong enough to clear the viruses within 8 to 24 months. Before they do, however, they may develop minor or low grade squamous intraepithelial lesions (LSL) that can then appear as an abnormality in a Pap smear. But as the virus is cleared, so usually is the low grade lesion. Patience is all that is needed to “cure” most of the early changes (termed dysplasia) caused by HPV in these young women.

Until recently doctors responded to mild and moderate Pap abnormalities in a sexually active adolescent or young woman with immediate reaction and action….we notified her that there was something “off” in the Pap smear and further testing was needed. (And she then called her Mom who invariably became hysterical.) We did colposcopy (an exam of the cervix with a microscope) and often followed this with biopsies. Then if the latter confirmed even mild changes we were taught to “catch and treat” immediately. We froze the offending cervix with cryotherapy to destroy the superficial “bad” cells or tried to destroy them with laser. (None of this killed the offending virus….we were treating the result not the cause.) And if the cells showed a more worrisome lesion we removed a part of the cervix with a procedure termed a LEEP or did a cone excision.

Well it turns out that early treatment in very young women was, in many cases, unnecessarily aggressive and harmful. The treatment could scar the cervix and lead to problems getting pregnant, maintaining a pregnancy to term (i.e. cause premature labor) and finally increase the risk of cesarean section.

Research on sexually active young women to see “what would happen if we left these early lesions alone” has shown that invariably the lesions do clear. Hence ACOG now recommends that gynecologists begin performing Pap smears in all women at the age of 21. The risk of missing a serious lesion in sexually active young women and adolescents is estimated to be 1-2 cases in a million. If Pap smears were done earlier, tens of thousands of minimally abnormal changes would be found and result in unnecessary procedures that could harm the future fertility and pregnancy in these young women.

ACOG also addressed the frequency of Pap smears in women who are older… No one wants to ignore the harm that high risk and non-cleared HPV’s can do over time. Hence the organization recommends Pap smears be performed every 2 years in women ages 21 to 29. And for women over 30, they feel it is probably sufficient to do the Pap smear every 3 years. (These women should already have a Pap history and are more likely to be in a mutually monogamous relationship.) To qualify for the 3 year rule a woman over 30 should have had 3 negative Pap’s. And negative Pap smears are most reassuring if HPV testing is also negative. (Note, I routinely order HPV testing in my patients when I do their Pap.)

Exceptions are made and Pap testing should be done more frequently for women over the age of 21 if they are immunocompromised, have been HIV infected, were treated for CIN2 or CIN 3 (high grade lesions) in the past or are DES exposed (their mother took DES while pregnant).

Remember if you are not in this risk group, if your Pap smears have been normal for many years, you do not have HPV and you are in a mutually monogamous relationship, nor have you had HPV in the past….you are not going to get cervical cancer unless you have a new “source” of HPV!

When it comes to stopping Pap smear testing….it’s a bit more complicated. Women aged 65 and older represent 14.3 % of the US population and have 19.5% of new cases of cervical cancer. In white women in the US the rates of new-onset of cervical cancer peaks in the 5th decade of life then decreases, in Hispanic women it is in the early 70’s and in Asian and Pacific Island ethnicity the incidence peaks in the late 70’s. The American Cancer Society recommends discontinuing Pap smears at 70; the US Preventive task Force has set the age at 65. ACOG suggests that if a woman over 65 is sexually active, and has more than one partner that she is still at risk and should get Pap smears. (Albeit she is less at risk than a younger woman because her cervical cells have undergone changes that make them less accessible to HPV caused mutations.) And women with a past history of abnormal Pap’s should continue screening until results are negative for 10 years.

Finally what about the women who have had a hysterectomy? If the cervix was not removed (a subtotal hysterectomy) you still need Pap smears with the same frequency as a woman who had not had this surgery. If however, the cervix was removed during the procedure (a total hysterectomy), then the only reason to continue having Pap smears is if the hysterectomy was done for a cervical high grade lesion or cancer. In this case the Pap can check for recurrence of the lesion in the vaginal cuff.

I know this all seems complicated. What I want to emphasize is that less frequent Pap smears does not mean less frequent pelvic, breast, or general exams. You will still receive annual reminders to come to see me (or whomever you go to for your gynecologic care). At that time we can discuss how often your Pap smear should be done. The rest of your exam can ascertain possible pathology in your breasts, uterus, endometrium, ovaries and hormones as well as any issues related to your general health (weight gain, diabetes, coronary vascular risk, hypertension, and bladder problems to name a few).
Women younger than 21 still need to discuss contraception, and if sexually active should be checked for STD’s, and taught how to prevent them. And if any woman has menstrual problems she should seek diagnosis and treatment. Women who plan to conceive should be seen and given appropriate preconception tests and advice.

The era of reproductive health sets the status for our entire lives. Once we enter menopause there are many more health and well-being issues we have to deal with. (Please note I haven’t even begun to talk about hormonal issues.) The cervix is just one part of our reproductive system. Pap smears save lives….but we are more than a cervix and need to maintain the health of the rest of our body.

This will hit the headlines on Tuesday, so I thought I would share the opinions. At this point I will choose to follow the ACOG recommendations and continue to suggest mammograms for my patients between 40 and 50 as well as breast self exam (BSE).

Response of The American College of Obstetricians and Gynecologists to
New Breast Cancer Screening Recommendations
from the U.S. Preventive ervices Task Force*

In the November 17 issue of Annals of Internal Medicine, the U.S. Preventive Services Task Force (USPSTF) updates its recommendations on screening for breast cancer in the general population (see www.annals.org), including the following:

• The USPSTF recommends against routine screening mammography in women aged 40 to 49 years. The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient's values regarding specific benefits and harms. (grade C recommendation)
• The USPSTF recommends biennial screening mammography for women aged 50 to 74 years. (grade B recommendation) 
• The USPSTF recommends against teaching breast self-examination (BSE). (grade D recommendation)

The American College of Obstetricians and Gynecologists, however, currently continues to recommend the following services:

• Screening mammography every 1-2 years for women aged 40-49 years
• Screening mammography every year for women age 50 or older 
• BSE; BSE has the potential to detect palpable breast cancer and can be recommended.

The College is continuing to evaluate in detail the new USPSTF recommendations and the new evidence considered by the USPSTF. Any changes to College guidance will be published in its journal Obstetrics & Gynecology.

Why did the USPSTF recommendations change?

Mammography in Women Aged 40-49 Years

In 2002, the USPSTF recommended screening mammography, with or without clinical breast examination, every 1-2 years for women aged 40 and older (grade B recommendation). The new USPSTF recommendations are based on a systematic evidence review by Heidi D. Nelson, MD, MPH, and colleagues and a modeling study by Jeanne S. Mandelblatt, MD, MPH, and colleagues published in the same issue of Annals of Internal Medicine.

The 2009 USPSTF judged that, although women in their 40s and women in their 50s benefit equally from routine screening mammography, women in their 40s experience greater harms from screening than women in their 50s. The harms assessed by the USPSTF were radiation exposure, false-positive and false-negative results, overdiagnosis, pain during procedures, and anxiety, distress, and other psychologic responses. Therefore, the USPSTF recommended routine screening for women aged 50-74 but recommended against routine screening for women in their 40s.

Breast Self-Examination

In 2002, the USPSTF judged that evidence was inadequate to make a recommendation on teaching or performing BSE. The new USPSTF recommendations are based on a systematic evidence review by Heidi D. Nelson, MD, MPH, and colleagues published in the same issue of Annals of Internal Medicine. This systematic evidence review identified two studies published since the 2002 recommendations. These studies found that teaching BSE did not reduce breast cancer mortality but resulted in additional imaging procedures and biopsies. Therefore, the USPSTF recommended against teaching BSE on the grounds that it has no benefit for women but places them at risk of harm.

What Should Fellows Do?

At this time, The American College of Obstetricians and Gynecologists recommends that Fellows continue to follow current College guidelines for breast cancer screening. Evaluation of the new USPSTF recommendations is under way. Should the College update its guidelines in the future, Fellows would be alerted and such revised guidelines would be published in Obstetrics & Gynecology.

The College continues to recommend that Fellows advise mammography screening for their patients aged 40 and older and that they counsel their patients that BSE has the potential to detect palpable breast cancer and can be performed. Fellows should be aware that the new USPSTF recommendation against routine screening mammography for women aged 40-49 (a grade C recommendation) has implications for insurance coverage, as some insurers will cover only preventive services rated as an "A" or a "B" by the USPSTF. Fellows should counsel their patients that insurance coverage for "routine screening" mammography may become variable and that patients should address this question with their insurers. These recommendations do not apply to high-risk women or patients with clinical findings, and they should be managed accordingly.

Interpreting the U.S. Preventive Services Task Force Breast Cancer
Screening Recommendations for the General Population

What do the USPSTF letter grades mean?

The USPSTF's recommendations are based on its assessment of net benefit—identified benefits minus identified harms. The USPSTF will only make a recommendation if it judges the available evidence to be of high enough quality that it can have high or moderate certainty as to the magnitude of the net benefit.

Interventions that are deemed to have substantial net benefit receive an A grade; interventions with moderate to substantial net benefit receive a B grade; interventions with small net benefit receive a C grade; interventions that have no net benefit (have harms that exceed the benefits) receive a D grade. If the evidence does not meet USPSTF standards, an "I statement" is issued.

Each letter grade is accompanied by a suggestion for practice. For A and B recommendations, the suggestion is to "offer/provide this service." For C recommendations, the suggestion is to "offer/provide this service only if other considerations support offering or providing the service in an individual patient." For D recommendations, the suggestion is to "discourage the use of this service." For I statements, the suggestion is to "read the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms."

Grade C recommendations highlight the need for individualized decision making that considers the patient's own assessment of benefits and harms. The American College of Obstetricians and Gynecologists strongly supports shared decision making, and in the case of screening for breast cancer it is essential. Surveys have shown that women are more concerned about their risk of breast cancer than heart disease, which is more common. Many women, after weighing the benefits and risks for their own particular situation, will choose to have screening mammography.

What is the College doing in response to the new recommendations?

The College, as a partner organization of the USPSTF, reviewed the draft recommendation statement and expressed concern regarding the implications of recommending against routine screening mammography for women in their 40s.
The College is continuing to evaluate in detail the new USPSTF recommendations and the new evidence considered by the USPSTF. The new recommendations and the evidence on which they were based will be reviewed by College committees that make recommendations on screening for breast cancer. Should the College update its guidelines in the future, Fellows would be alerted and such revised guidelines would be published in Obstetrics & Gynecology.

Why did the USPSTF recommend against routine mammography for women in their 40s?

The new USPSTF recommendations are based on a systematic evidence review by Heidi D. Nelson, MD, MPH, and colleagues and a modeling study by Jeanne S. Mandelblatt, MD, MPH, and colleagues that were published in the same issue of Annals of Internal Medicine as the recommendation statement. Based on these analyses, the 2009 USPSTF judged that although women in their 40s and women in their 50s benefit equally from routine screening mammography, women in their 40s experience greater harms from screening than do women in their 50s. Therefore, the USPSTF recommended routine screening for women aged 50-74 years but recommended against routine screening for women in their 40s.
The USPSTF's evaluation of the evidence found that the benefit to women in their 40s was virtually the same as the benefit to women in their 50s. The relative risk of breast cancer mortality for women randomly assigned to mammography screening was 0.85 in women aged 39-49 years and 0.86 in women aged 50-59.

Rather than benefit from screening, women without cancer who undergo mammography, additional imaging, and biopsies may incur harm. These outcomes were more common in women in their 40s (see Table). In addition, because the prevalence of breast cancer is higher in women in their 50s and because younger women are more likely to have dense breasts that may be difficult to assess on mammography, women in their 40s had more false-positive mammograms and underwent more additional imaging than women in their 50s.

Table. Age-Specific Screening Results from the Breast Cancer Surveillance Consortium

*Data are from a single screening round in regularly screened women. Because the Breast Cancer Surveillance Consortium incompletely captures additional imaging and biopsies, these rates may be underestimates.

Data from: Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med 2009;151:727-37.

The number needed to invite for screening (over several rounds of screening and at least 11 years of follow-up) to prevent one breast cancer death in women aged 39-49 was 1,904, compared with 1,339 in women aged 50-59.
The USPSTF also considered pain and psychologic responses as harms. The USPSTF notes that "anxiety, distress, and other psychosocial effects. . . fortunately are usually transient, and some research suggests that these effects are not a barrier to screening. . . Other potential harms, such as pain caused by the procedure, exist but are thought to have little effect on mammography use."

The Mandelblatt modeling study assessed six separate models of the effects of screening mammography using the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET). It states: "If the goal of a national screening program is to reduce mortality in the most efficient manner, then programs that screen biennially from age 50 years to age 69, 74, or 79 years are among the most efficient on the basis of the ratio of benefits to the number of screening examinations. If the goal of a screening program is to efficiently maximize the number of life-years gained, then the preferred strategy would be to screen biennially starting at age 40 years."

How might women be affected by the new recommendations against routine screening mammography for women in their 40s?

U.S. Census data demonstrate that there were 22,327,592 women aged 40-49 years in the United States as of July 1, 2008. Based on Surveillance Epidemiology and End Results Program (SEER) data, breast cancer deaths expected over 10 years were estimated at 204 deaths per 100,000 women aged 40-49 years (including both screen-detected and nonscreen-detected breast cancer). This 10-year death rate leads to an estimate of 45,492 deaths of U.S. women aged 40-49 years from breast cancer over 10 years. With a relative risk of 0.85 for breast cancer mortality for women in their 40s screened by mammography, an estimated 38,668 deaths would occur in a screened population over 10 years, approximately 6,800 fewer deaths than expected with the 10-year death rate. The fewer deaths expected with screening compared to the predicted deaths demonstrates the significant benefit of screening on mortality in this age group.

Why did the USPSTF recommend against teaching BSE?

The new USPSTF recommendations are based on a systematic evidence review by Heidi D. Nelson, MD, MPH, and colleagues published in the same issue of Annals of Internal Medicine. This systematic evidence review identified two studies published since the 2002 recommendations. These studies found that teaching BSE did not reduce breast cancer mortality but resulted in additional imaging procedures and biopsies. Therefore, the USPSTF recommended against teaching BSE on the grounds that it has no benefit for women but places them at risk of harm.

Who uses the USPSTF recommendations?

The main audience for the USPSTF recommendations is the primary care clinician. The congressional mandate establishing the USPSTF charges it with reviewing "the scientific evidence related to the effectiveness, appropriateness, and cost-effectiveness of clinical preventive services for the purpose of developing recommendations for the health care community."

However, although the USPSTF recognizes that its recommendations also have relevance for and are widely used by policymakers, managed care organizations, public and private payers, quality improvement organizations, research institutions, and patients, it also recognizes that its recommendations are only part of what needs to be considered in setting health care policy. The disclaimer that accompanies these new recommendations reads: "The USPSTF recognizes that clinical or policy decisions involve more considerations than this body of evidence alone. Clinicians and policymakers should understand the evidence but individualize decision making to the specific patient or situation."

How will the USPSTF recommendations be used in health care reform?

Health care reform legislation being considered in the House and Senate seeks to ensure coverage of preventive services as part of a basic benefits package in all health insurance plans, as well as patient cost-sharing protections for these services. In determining which services should be covered, the bills rely heavily on the USPSTF recommendations. At a minimum, covered preventive services would be those that receive an A or B grade from the USPSTF.

It is vital that covered preventive services not be limited solely to USPSTF grade A and B recommendations. The USPSTF has not issued recommendations for many vital preventive services in women's health care, such as preconception care, family planning counseling and services, and bundled services such as the annual well-woman examination. The USPSTF only makes and updates a handful of recommendations each year, far too few to address clinically appropriate preventive services that ought to be covered by any plan.

I’ve been inundated with phone calls and questions about articles that have appeared in the media which have suggested that there is a link between hormone use and lung cancer. Lung cancer is the second most common cancer in women (first is breast cancer) and is the leading cause of cancer deaths. We all know that tobacco smoking is the major risk for this dreaded disease and indeed 84% of male lung caner cases can be attributed to smoking. However, only 46% of cases in women seem to result from cigarettes. Researchers have been searching for other causes including supplemental hormones. Approximately 24% of women older than 40 years are currently using hormones in the United States. So if there is an association it could be huge!

Multiple studies have looked at a possible link between hormone use and lung cancer. The results are fairly inconsistent. Here are a few:

• A study of 23,244 Swedish women with 6.4 years of follow up, found a slight increase risk in lung cancer. This was calculated as an odds ratio of 1.3 (women who did not smoke were 1.0) so this means there was possible 30% increase in risk above that of non smokers.
• The Women’s Health Initiative that included 16, 000 women on Prempro found no association between post menopausal hormone therapy and lung cancer, with follow up of 5.2 years.
• The Cancer Prevention Study II Nutrition Cohort which consisted of 72,772 women found a decrease lung cancer risk associated with hormone therapy for post menopausal women. This study had 12 years of follow up.
• A case control study in the United States with 499 lung cancer cases and 519 control (that means the number of women with lung cancer were compared to those who did not have cancer) as well as a German study with 811 lung cancer cases and 912 controls found either no significant association or protection against lung cancer for “ever use” of female hormones.
• A recent study published in Menopause: The Journal of the North American Menopause Society included 2,861 women who were aged 31 to 79 years at enrollment and were followed for a 31 year period of time. They were interviewed every 4 years and asked whether they smoked, how much, if they had quit, for how long and if they were taking oral contraceptives, estrogen, or pills for hot flashes, or to regulate periods. The findings showed that 35.8% were using hormones at time of enrollment. The hormone users were also more likely to be current or former smokers than those who were not taking hormones. Eighty seven women developed lung cancer. There was no association between hormone use and lung cancer in general. But (and there I always a “but” in medical studies), a separate calculation for the women who were 55 years and older, found that lung cancer risk was increased with an odds ratio of 1.58, whereas in women younger than 55 years, lung cancer risk was reduced with an odds ratio of 0.44.

The statisticians feel that overall this is a null finding….in other words not significant for or against the effect of hormones on lung cancer. The conflicting results in all these studies certainly leave pause for concern and need for future large and long term research.

It is estimated that it takes 18 to 30 years from time of smoke exposure to lung cancer development. In the Ranch Bernado study hormone users were slightly heavier smokers and had longer duration of smoking, which may have caused that slight increase in lung cancer in the older women who used hormones. At this point my advice is not to smoke and quit if you do; but if you don’t you probably should abstain from hormone use

So there I was giving a lecture “somewhere” other than California. The organizers took me to dinner in a “fancy” French restaurant. The private dining room was booked for a wedding reception and as the bride arrived with her attendants I could not help but notice two young women who were visibly pregnant… and smoking. To make matters worse one held a nearly empty bottle of beer. I so wanted to go up to these women and suggest that they were increasing their risk of preterm labor, diminishing their progeny’s physical and mental growth and ultimately risking fetal and/or neonatal death, but of course, did not.

I strongly advise women to quit cigarette smoking before they conceive (or before they start to smoke, whichever comes first) for their own health. But if it’s too late, I should have a method to offer them on how to quit while they are pregnant. Although I have never been a smoker, I understand from many friends and family how difficult it can be. “Cold Turkey” describes my lack of cooking skills at Thanksgiving and is also the preferable way to quit while pregnant, but may just be too difficult.

Thank goodness, the data from a study of 100,000 pregnant women in Denmark and their offspring has shown a reasonable substitute, nicotine replacement therapy (NRT). Despite the fact that women who used nicotine replacement therapy were more likely to be over the age of 35 and drink two or more alcoholic drinks per week during pregnancy, they were NOT at increased risk of stillbirth compared to women that neither smoked nor used NRT. The women who continued to smoke throughout their pregnancy had a significantly increased rate of stillbirth as well as the risk of having a child with oral cleft, malformations of the circulatory system and/or digestive system. Those who stopped but used NRT were at reduced risk.

The important fact is that although NRT does contain nicotine, it doesn’t have the other 2999 chemicals that are present in cigarette smoke (yuck!). The American College of Obstetrics and Gynecology has stated in an official opinion that although, quitting cold turkey is best, women who cannot quit smoking without assistance may use NRT during pregnancy. They recommend that NRT products that provide intermittent nicotine — such as gum or lozenges– be tried before resorting to products that provide a constant dose (the nicotine patch)

Perhaps I should have offered one of these products to those pregnant and smoking women that were in the restaurant.

I spend a lot of time trying to convince my patients to get screened for colorectal cancer. Somehow pap smears , mammograms, blood tests, urine tests and yes the occasional CT or even MRI scan seem doable and require little preparation (at least physiologically). But at the mention of a colonoscopy there is a reticence that seems universal. (After I write this I have to check to see if I am due for mine.) The New England Journal of Medicine presented a “Clinical Practice” article in its September 17th, 2009 issue. Since most of you don’t include this journal in your regular subscriptions (although it is currently available on Kindle) I though that it was a good time to go over the reasons for and methods available to screen for colorectal cancer.

Colorectal cancer is the second leading cause of cancer death in the United States. There will be approximately 147,000 newly diagnosed cases of colorectal cancer and 50,000 deaths from this disease in 2009. There is a gender difference and in women it is the third leading cause of cancer death, after lung cancer and breast cancer. The fact that it comes in third should in no way diminish our concern…remember very few men develop breast cancer. And if you wait for symptoms to occur, it may be too late to affect a cure….in many cases this disease strikes women who have no changes in their bowel habits!

Some of us may be at higher risk than others: If you have a first degree relative who had colorectal cancer before the age of 50 you may have an inborn genetic mutation that will predetermine a high risk for this cancer. There are gene tests (done as blood tests) that can ascertain if you have inherited colorectal cancer syndrome. If you are positive for these specific mutations, you will need very intense screening and perhaps surgery. If a first degree relative had this cancer at 50 years of age or older your lifetime risk doubles and screening should be started at 40 or 10 years younger than the age that your family member was diagnosed with this cancer. And if you have a history of chronic ulcerative colitis or colitis due to Crohn’s disease your risk increases and you should begin surveillance with colonoscopy 8 to 10 years after you received the diagnosis.

So now that we have established that colorectal cancer, like breast and cervical cancer requires screening; what are the stats on the success of the various methods? Let’s start with the “easiest”, the stool tests for occult (not visible to the naked eye) blood. Its advantage is that it can be done in the privacy of your home bathroom. There are 2 types of tests, the first requires 3 stool samples and is not specific for human hemoglobin. (You need to abstain from various foods , especially red meat). The second type may require just one annual stool sample. It specifically tests for human hemoglobin. If either test is positive, you will need follow up with a colonoscopy, to see what is there (causing the minute bleeding), and if necessary, a biopsy of a polyp or lesion to ascertain if it is cancerous or precancerous.. Persons with positive occult- blood tests have a risk of cancer that is 3 to 4 times higher than those with negative tests. The combination of annual stool test followed by colonoscopy probably picks up 50 to 75% of cancers…but there is no guarantee that these cancers are found at an early stage. Indeed if an advanced polyp that is destined to become cancer is present, the stool test for blood may be negative 50 to 80% of the time.     What I found interesting from a public health cost perspective (which will be factored into health care reform) is that the expense of screening with annual fecal blood tests, reminder systems and colonoscopy in patients with positive tests is just as costly as screening with colonoscopy!

There is a new stool test that may turn out to be more accurate than the one for occult blood. It detects specific DNA mutations from cancer cells excreted in the stool. The test is expensive and right now researchers don’t know how frequently it should be performed.  They also are not sure about the sensitivity of this test, i.e. whether it will pick up advanced, potentially precancerous adenomas.

Barium enema has been found to be inadequate for diagnosing precancerous lesions and is now rarely used for screening.

Now we come to the controversy surrounding CT imaging of the bowel. It, like colonoscopy requires complete bowel preparation (clear liquids for at least 24 hours, ingesting those diarrhea inducing solutions or pills and an evening spent near and on the toilet). Studies have shown that expert radiologists can identify 90% of polyps that are 10mm or larger.  But 14% of the time the “polyps” that they diagnose are not actually there when follow-up colonoscopy is performed (i.e. false positive). There also is a concern that the scan may not find flat polyps that can be cancerous or precancerous. The current estimate is that of all those who have this test, 15 to 25% will be referred for subsequent colonoscopy. (And remember this requires a second, unpleasant bowel prep!). Moreover, CT scan frequently does not demonstrate a polyp that is less than 6mm. At this diameter the polyp usually is not cancerous. However small can grow to large and the method of follow-up for small polyps presents a dilemma.

The radiation involved with these scans should also be factored in. Each scan may be fairly low dose, but if done repeatedly or other CT scans are done for other reasons, cumulative radiation can increase future risk of cancer. And finally, whenever scans are done, a lot of “needles in a haystack” may be found, often requiring invasive but ultimately unnecessary interventions. Up to 69% of persons who undergo screening with CT colon scans have at least one finding outside the colon. Studies show that further evaluation is performed in 5 to 16 % of persons who undergo this CT screening.

By now most of you realize that looking at just the lower portion of the colon with sigmoidoscopy is like doing a mammogram on one breast. This uncomfortable procedure (it requires enemas for preparation, and rectal insufflation with air) misses more than 30% of cancers that are present higher up in the colon…especially in women or patients over the age of 60.

Finally we get to the gold standard for colorectal cancer screening, colonoscopy. If you are screened (and have no known risk) you have a 0.5 to 1% chance of having colon cancer found with this test and a 5 to 10% chance of detection of advanced polyps that could become cancer and which can be removed at the time of the screening procedure.. This represents a huge (when in comes to cancer) window of opportunity to diagnose an impending “this can be bad” lesion and prevent cancer. Not only has a future disaster been averted, you are now classified as a polyp “grower” and you and your doctor know that you need to be followed with frequent screening.

As with any test, nothing is perfect. According to the New England Journal review article 2 to 12% of lesions that are 10 mm or larger in diameter may be missed during a colonoscopy. In order for the exam to be complete all the polyps that are seen should be removed. And “when colonoscopy is performed by properly trained endoscopists the risk of serious adverse events is 3 to 5 events per 1000 colonoscopies.” (This includes perforations and bleeding).

Colonoscopy affects every program because it is the last and most effective way to ensure that colorectal cancer is neither present nor impending. Guidelines from the American College of Gastroenterology recommend colonoscopy as the preferred screening test. If one or more polyps are found (which, if we include small polyps, occurs in 20 to 50% of patients), the interval for repeat colonoscopy varies according to the pathologic findings (usually between 1 and 5 years). I f no polyps are present and there are no risk factors, the colonoscopy can be repeated every 10 years.

There are two addendums to what I have just written. It appears that both black men and women develop polyps and colon cancer at a younger age and have a higher mortality from colorectal cancer than white individuals. So the current recommendation by The American College of Gastroenterology is to initiate screening in African Americans at the age of 45. And finally since even colonoscopy can miss the occasional polyp and recent studies show have shown that precancerous polyps can develop in less than 10 years, many gastroenterologists prefer to repeat colonoscopy every 7 years.

Well, this has certainly been a lengthy review. But after reading it I hope you don’t give your doctor or me that look of “you-must-be-kidding:” when we suggest you are due for your colonoscopy.  The colon you save may be your own!

Several times a week I receive a message from my nurse: “Ms.… called and is upset; she was informed by the mammogram center that she should return for additional views and an ultrasound”. Often the message goes on to say “She wants to know if she should go off her hormones?”

I can give my patients some general reassurance about these recalls. Up to 10% of women who undergo screening mammography are advised to return for additional imaging. That large percentage does not, however, suffice to allay the anxiety produced by this “your breasts warrant more scrutiny” report. What does help is informing my patients that 95% of these recalls are not associated with a diagnosis of breast cancer in the following year. (Remember screening involves annual mammograms, and a normal exam one year does not guarantee that the next will be as reassuring.)

What can make a mammogram difficult to read? Dense breasts probably rate as the number one tough-to- look-though-and-diagnose tissue and issue. The radiographer is searching for areas that appear solid or have certain kinds of spider-like calcifications that appear on x-ray as white against a fairly homogeneous black and gray background. But if the breast tissue contains densely packed glands with little fat between them the entire breast appears white on the image and it’s difficult to delineate bad white from good white. The younger we are the denser our breasts (They are also perkier!). Hence it’s particularly hard to diagnose an abnormal lesion with mammography imaging in a woman who is under the age of 40. Breast cancer is usually a cancer of longevity…which means the older we are the more likely we will develop this type of cancer. So at least we can reassure ourselves that as our age increases the “look-through” potential of our basic screening test improves.

Mammograms are only indicated in young women (before the age of 40) if they have a family member who has developed breast cancer before the age of 50, they themselves are known to have a mutation in the BRCA gene, they have had radiation to the chest wall before the age of 30 or, of course, if they present with a palpable mass. And in these young, high risk women, it is probably advisable to add ultrasound and in certain instances, an MRI.

There has been much ado over the fact that menopausal hormone therapy (HT) with estrogen and progestin is associated with an increase in breast density. And since dense breasts are more difficult to “read” (medically reported as a lower sensitivity and specificity), the question has been raised: should women go off their hormones one or two months before they have their mammogram? Would this help eliminate that 10% possibility of having to go through the anxiety, inconvenience and cost of additional tests?

A recent article in The Annals of Internal Medicine sought to answer this question. In a federally funded trial, investigators tried to recruit women who were using hormone therapy at the time of their screening mammograms and were then still using it when due for their next one. Of the 4,884 women who “qualified” for the study, two thirds declined to participate because they didn’t want to stop their HT use. (I guess the fear of developing hot flashes, night sweats or sleep disorders, even if temporary, overcame any desire to help research or potentially eliminate a difficult mammogram reading.) Those that agreed to participate were randomized to one of 3 groups; no suspension of HT, 1 month suspension or 2 months of suspension of HT before their screening mammography. The final study of willing participants included 1471 women, their mean age was 60 and 92% were Caucasian.

And what did they find?… Suspending hormone therapy had no impact on the recall rate. It was 11% for the no HT suspension group, 12% for the 1-month suspension group and 10% for those who went off their hormones for 2 months prior to their mammogram. Not surprisingly HT suspension was associated with a significantly greater likelihood of hot flashes (reported by half of the women at baseline and more than 85% of those who temporarily stopped their HT).

Bottom line: Stopping hormone therapy for a month or two before having a mammogram does not lower recall rates. Moreover, most women who are on HT are not willing to do this.

“I had surgery for an ovarian cyst”… a not uncommon statement in the medical histories I get from patients. This is usually followed by the exclamation: “Thank goodness it was benign!” The question is how many of these women underwent unnecessary surgery for something that was benign?

Most cysts in young women (we’re talking reproductive age here) are “functional”, a term used to describe furniture and clothes design…but when used as a gynecologic adjective it connotes a cyst that is formed during the monthly cycle. Follicular cysts develop as the ovary tries to do its duty and create a dominant follicle from one of its primordial oocytes during the first 2 weeks of the cycle. Once ovulation occurs a remnant of that follicle can form a second type of functional cyst termed a luteal cyst. Let me explain:

At the time of puberty the ovaries contain about 400,000 primordial or preformed oocytes (future eggs). Each month one of them usually gets to come forth to fulfill its destiny to grow and develop into a mature egg while thousand more die….sort of depressing, but this is the survival of the fittest egg. (Just consider how many sperm die with every ejaculate and perhaps you won’t feel so bad. But wait, sperm get produced anew every 3 month while we have a fixed number of eggs and once they are used up we can’t make anymore. So there is an ovarian woe in this saga. Our finite number of eggs also explains the hormonal phenomena of perimenopause and menopause, but I diverge…)

A small amount of fluid surrounds the developing egg so that the developed follicle becomes a little cyst on the outer circumference of the ovary. It produces estrogen. At ovulation the follicle ruptures and the egg is extruded. Some women feel this rupture as a mid-cycle pain called by the appropriate onomatopoeic term “mittlesmirz” (pain in the middle). If the cyst becomes large (too much fluid accumulates) and/or grows, it creates a functional follicular cyst.

Once the egg has been released (and potentially may be fertilized by sperm swimming in the tubal vicinity), the emptied follicle changes its identity and becomes a corpus luteum. This too is a small cyst that goes on to produce progesterone and estrogen; hormones that are needed to build up the lining of the uterus so that it can support a developing embryo. In the absence of a pregnancy the corpus luteum dwindles and yes dies; the uterine lining or endometrium is sloughed (the menstrual period) and the entire cycle starts all over again. But if that corpus luteum does not regress and instead swells or bleeds into itself (it has a terrific blood supply) it too can create a functional cyst called a luteal cyst.

Before ultrasound was extensively used, a woman who presented with a mass on the ovary, pain or an enlarged “something” in the area of the tubes or ovaries (called the adnexa), was often subjected to surgery. Even with the advent of ultrasound…if the cyst was big enough or had areas that were not translucent, surgery was often performed either by laparoscopy or an open abdominal procedure. The cyst was removed (cystectomy), or in some cases, the ovary was excised (oophorectomy). After all, the surgeon was already in there and that was the best way to ensure it would be properly diagnosed and “cured”. Any of these procedures could lead to subsequent scarring, pain and/or infertility.

In the 60’s and 70’s doctors noted that women who took oral contraceptives (in doses that were higher than those used today) seemed to have a lower incidence of these functional cysts. The thought was that if ovulation was suppressed there would be no reason for functional cysts to develop. (New data shows that low dose birth control pills do not substantially decrease a woman’s risk of ovarian cyst formation.) This theory that the Pill will stop cyst formation has continued to be used to treat cysts and make then “go away”.

Not so….according to a recent Cochran report that was abstracted in the Journal of the American College of Obstetricians and Gynecologists. The Cochran Review analyses the most relevant and well conducted studies that have been published in peer reviewed journals. The authors then review these studies for accuracy and statistical relevance. Seven randomized controlled trials from four countries were found; the studies included a total of 500 women. The analysis showed that “treatment with combined oral contraceptives (which contain both estrogen and progestin) did not hasten the resolution of functional ovarian cysts is any trial.” And indeed “most cysts resolved without treatment within a few cycles”. This included cysts that developed spontaneously and those that occurred after ovulation induction with fertility medications. (The forced feeding of the ovaries with fertility drugs causes the development of multiple follicles and can result in cysts). They found that most of the cysts that did not regress after a few months of being left alone were endometriomas (blood filled cysts that occur with the disease called endometriosis) or cysts that developed from the fallopian tubes.

So does your physician have to go after those cysts that she or he feels and then “sees” with ultrasound during routine exam? The answer in most circumstances is no. Nor do we have to treat these functional cysts with oral contraceptives to get rid of them. A simple “wait and recheck” in a 2 or 3 months is appropriate.

Bottom line: There is no need to freak at the mention of an ovarian cyst that has developed while you are in your reproductive years. It will probably go away in a month or two. Surgery is indicated only if you develop significant pain (very rarely cysts can twist or bleed) or if the cyst persists.

You’ve made that appointment for your yearly checkup; you are a patient patient as you peruse expired periodicals in the waiting room. You then have to pee into a cup, put on a ridiculous gown that doesn’t close and when the medical practitioner arrives, go though an exam that requires an undignified lithotomy position. (You know, with your feet in stirrups, your legs apart and your tush at the end of the exam table). The least that you should expect from all this is reassurance that you do not have cancer, or in the worst case scenario that the cancer has been found at an early stage and can be successfully treated. There are pap smears and HPV tests, pelvic bimanual examinations which allow the examiner to palpate pelvic abnormalities such as tumors, cysts or fixed, scarred and painful masses, blood tests and, of course, ultrasound. All these plus a carefully obtained medical history are used to rule out cervical and uterine cancer (as well as inflammation, benign cysts, and endometriosis), but the definitive tests for ovarian cancer still eludes gynecologists.

A quick review: Ovarian cancer is the leading cause of gynecologic cancer deaths, not because it is so prevalent but because it is usually found only after it has spread to other organs in the pelvis, abdomen or distant parts of the body. Our lifetime risk of developing this cancer is 1.4% which means that 1 in 71 women will develop ovarian cancer in their lifetime. One in 95 will die from it. Ovarian cancer is a cancer of older age…two thirds of cases occur after the age of 55…and the older we are the greater that risk.

Whenever you give your family medical history you are asked if you have first degree relatives (parents, siblings, and/or children) who have had or died from ovarian or early onset breast cancer. If so, this can triple your risk. And the risk of ovarian cancer is highest for BRCA gene mutation carriers. Testing for this mutation is recommended if you have a significant family history of ovarian cancer, female or MALE breast cancer, or multiple relatives with breast cancer and/or any of these combined with a high incidence of prostate or colon cancer. Mutations in the BRCA1 gene increase lifetime risk of ovarian cancer to 30 to 46% while mutations in BRCA2 are somewhat less of a risk but still high at 12 to 20 %. There are 3 sites for single mutations in these genes that are found in 2% of individuals who are Ashkenazi Jews (from Eastern Europe). So if you are Jewish and your ancestors came from Eastern Europe (this describes me)) and there is a relevant history in your family of these cancers, I would highly suggest you get the 3 site testing for the BRCA mutation.

(An aside… if there is no breast or ovarian cancer history and you are an Ashkenazi Jew, testing is not recommended “just to make sure”. I queried several physicians while visiting Israel a few weeks ago as to whether BRCA testing was routinely carried out in women who were of Ashkenazi Jewish heritage and the answer was a resounding no. But they do perform genetic testing on pregnant women for a wide range of potential diseases that are more prominent in the newborns of the families with this heritage. As our government discusses medical reform I would hope that they look at the system in Israel….where nearly everyone has medical coverage and choice options are available.)

So how can we diagnosis this relatively rare but often deadly cancer? Are there symptoms? Yes, but they are fairly non specific and are often ignored. They include pelvic or abdominal pain, urinary frequency or urgency, increased abdominal size (not just overall weight gain), bloating or difficulty eating or feeling full more than 12 times in a month. Yes this could be indigestion, a persistent urinary infection, overactive bladder or gas….but studies have shown that when women diagnosed with ovarian cancer where asked about a history of these symptoms, many had them. So if you are over 50 and experience these symptoms, see you doctor.

What about routine screening? Why can’t we simply do a pelvic exam, blood test, ultrasound or some combination of all these and find the disease at an early stage? After all, when ovarian cancer is confined to the ovary (stage 1) the 5 year survival is 90%, but falls to 33% when the diagnosis is made at stage III or IV.

A recent report in The New England Journal reviewed the current status and recommendations for ovarian cancer screening. First they reported on the tumor marker CA-125. This is a protein found at greater concentration in ovarian cancer cells than other cells and is elevated in blood tests of 80% of women with advanced stages of ovarian cancer. But there are some severe limitations to screening with this protein. High levels can be found in 1 to 2 % of normal women. CA-125 is elevated in only 50% of stage I cancers and it can be falsely elevated due to many benign and malignant conditions (endometriosis, fibroids, pelvic inflammatory disease, hepatitis, pregnancy, menstrual bleeding, recent abdominal surgery, breast cancer, pancreatic cancer, colon cancer, lung cancer and endometrial cancer). Currently, because it is so nonspecific, the American Cancer Society as well as the American College of Obstetricians and Gynecologists does not recommend its use as a routine screening test for ovarian cancer. They do feel it’s useful if an ovarian mass is found or if there is a significant family history putting a woman “at risk”. Most insurance companies and Medicare agree and won’t pay for a CA-125 test when it is ordered without a very specific indication!

There are other markers that have been investigated, some based on particular proteins produced by tumor cells or the presence of certain growth factors but to date, they have not been validated in large populations of women in randomized prospective studies. (Translation: Are the women who are given the tests diagnosed earlier than control women who are not tested?)

Ultrasound done with a vaginal probe (transvaginal) has been a mainstay for viewing pelvic tumors. So why not simply perform transvaginal ultrasounds on all women, especially those over 50? Multiple studies have unfortunately demonstrated that this type of imaging has not been as successful as we would wish. The positive predictive value has been reported to range from a mere 1% to 27%; which indicates that many of the women in whom a suspected tumor was found with ultrasound did not have ovarian cancer. And some had unnecessary surgery that resulted in surgical, medical and psychological complications as well as significant financial cost.

The New England Journal of Medicine article reviews several large studies. One included 25,327 women who were at average risk for ovarian cancer and who had annual transvaginal ultrasound. Among women with suspicious findings 364 patients underwent removal of the abnormal ovary but only 29 were indeed cancerous and only 14 (48%) of these were found early at stage I.

And what if women had both tumor marker blood tests and ultrasound? So far an American study has been equally disappointing. It is called the Prostate, Lung, Colon and Ovarian Cancer Screening Trial. Final results won’t be issued until 2014. To date a total of 34,261 healthy women between the ages of 55 and 74 have been randomly assigned to undergo either annual CA-125 testing plus transvaginal ultrasound or to receive “usual care”. Their test results were considered positive if the CA-125 was above 35IU and/or their ultrasound showed an enlarged ovary (it should shrink with age) or a cyst with solid areas. During 4 years of screening, 3388 women had positive results and 1170 or 34% underwent surgery with removal of the one or both ovaries. Only 5.1% of those who had surgery were found to have cancer and 72% of these cancers were stage III or IV. Moreover, 29 cases of ovarian cancer were diagnosed during the study period and were not detected by screening! In statistical terms (and we all have to use these) the positive predictive value of positive screening was only 1.0 to 1.3% during the 4 years of the study.

Bottom line: If you are not at what is deemed “at increased ovarian cancer risk” having a CA-125 blood test or a transvaginal ultrasound to screen for this cancer is not recommended by any of the major gynecologic or cancer societies. These tests may allow you (and your doctor) to feel that you are proactive but neither guarantee that you don’t have an early stage ovarian cancer nor do they reassure you that you won’t receive a future diagnosis of late stage ovarian cancer. If you are at risk because of family history, consider genetic testing. The current recommendation for BRCA positive women is to undergo surgical removal of the ovaries between the ages of 35 and 40 at the completion of child bearing or at the earliest age at which cancer was diagnosed in affected family members. If women who are BRCA positive chose to wait for surgery, the Comprehensive Cancer Network recommends CA-125 and vaginal ultrasound every 6 months although no one is sure that this will increase survival rates. Finally, if you have signs or symptoms of ovarian cancer (pelvic mass, pelvis or abdominal bloating, urinary frequency or urgency, increased abdominal size, bloating, difficulty eating or feeling of fullness) see you doctor… ultrasound and CA-125 may be warranted. When I perform these tests on my symptomatic patients I warn them that they may, however, be falsely positive or negative. Hopefully, in the future, my colleagues and I can do better.

By now (I would hope) we all know that there is a strong recommendation that all young girls and women get the HPV vaccine (Gardasil) to protect them from 4 types of human papilloma virus infection. A quick review: two of the types (16 and 18) are responsible for 70% of cervical cancers, as well as vaginal and anal cancer whereas the HPVs numbered 6 and 11 cause genital warts. The efficacy of this vaccine has been tested and supported by sufficient evidence to warrant FDA approval and CDC recommendation for its use for girls, adolescents and young women up to the age of 26. The protection will always be maximal for sexually naïve young women (a medical term that means they have not had sexual intercourse or other sexual activity which would foster HPV transmission).

The greatest incidence of HPV infection occurs within 5 to 10 years of first sexual experience. But even if such an infection should occur the chance that all the HPV types are present is very slim (see another article I wrote for this web site). Hence we continue to immunize young women when the opportunity arises (i.e. they are seen by an appropriate medical provider and they or their parents consent to this series of three shots given over a period of 6 months).

If we give the HPV vaccine to young women even if they have been sexually active or have evidence that an HPV caused disorder exists, why shouldn’t “older” women receive the vaccine and be granted some degree of immunity?

Women are waiting longer to get married (most of my patients are over 26 when they are ready to commit) and as we all know divorce rates are high. Indeed in the USA nearly 40% of men and women have married and divorced by the age of 55 and more than 25% of these people have remarried at least once. So without being judgmental lets just acknowledge that at least half of us will have new partners after the age of 26. Do the current HPV vaccine recommendations constitute age discrimination?

A large study sponsored by the pharmaceutical company Merck (they developed the quadrivalent or 4 type HPV vaccine called Gardasil) has recently been published in the journal Lancet and suggests that women in their late 20’s, 30’s and 40’s could benefit from prophylactic HPV vaccination. The study enrolled 3819 women between the ages of 24 and 45 in 38 international study sites. The criteria for entering the study were that they were not pregnant, had no history of genital warts or cervical disease. Roughly half received the vaccine while the other half received a placebo shot. They were then checked at day 1 (when they received the injection) and months 7, 12, 24, 36 and 48 with a pelvic examination and swabs taken from the cervix, vulva, and perianal areas to test for HPV. The women also were given Pap smears and their blood was tested for antibodies to the 4 vaccine type anti-HPV antibodies (which could have been silently present from previous infection but if not, should have appeared subsequent to the vaccination).
Those who developed an abnormality on Pap smear underwent colposcopy (a microscopic exam) and when necessary a biopsy and treatment. The study was meant to continue for 4 years, but after 2 years the researchers reported the following: The vaccine was 90.5% effective in preventing disease or infection related to HPV 6, 11, 16 and 18 (there were 4 cases out of 1614 treated women vs 41 in 1607 in the placebo group). And 83.1% effective in preventing disease or infection related to HPV 16 and 18 alone. (Remember those are the types that are most likely to cause genital cancer).

Clearly most of these women were not sexually naïve, the mean age of first sexual intercourse before enrollment was 19. Indeed 33.3% of the women were found to be positive to HPV 6, 11, 16 or 18 by blood testing or DNA cervical testing at the onset of the study. Most of these women were positive to only one HPV type, 1% of them were infected with two of the types in the vaccine and less than 1% were infected with 3 vaccine HPVs, while none of the women had all 4. Translated, this means that two-thirds of the women were susceptible to infection with all 4 of these HPV types, and of the remaining one-third, the current HPV vaccine could still protect them against the other three types of HPV.

Just in case you now wonder if the study is ethical…and what will happen to those women who did not receive the vaccine…the women in the placebo group will be examined every 6 months and treated if necessary. ( This is probably better than the care that most women in the USA receive). At the end of the trial the vaccine will be offered to all the participants.

This study has only 2 years of follow-up. The CDC and other organizations will probably wait for the final 4 year results before making substantial changes in their vaccine recommendations. And in this economy we also have to consider cost and insurance coverage. (The series of 3 shots usually run more than $400). But so far the results are significant.

I currently do not suggest HPV vaccination for all my patients in the 26 to 45 age group; however I will no longer exclude this vaccination for women who are at risk for HPV infection, no matter what their age!