Cervical Cancer Screening Update: on Pap Smears, Liquid-based Cytology and HPV

The latest issue of the Annals of Internal Medicine contains 2 noteworthy papers on cervical cancer screening. The first, a systematic review of studies commissioned by the USPSTF, looked at 3 methods for evaluating abnormalities in women over 30 years:

high-grade cervical cell dysplasia (Dr. E. Uthman, Wikimedia Commons)

1. Conventional cytology (as in a Pap smear; the cervix is scraped and cells splayed onto a microscope slide for examination);

2. Liquid-based cytology (for LBC, the NHS explains: the sample is taken as for a Pap test, but the tip of the collection spatula is inserted into fluid rather than applied to slides. The fluid is sent to the path lab for analysis);

3. Testing for high-risk HPV (human papillomavirus). Currently 3 tests have been approved by the FDA in women with atypical cervical cells or for cervical cancer risk assessment in women over the age of 30: Digene Hybrid Capture 2 (manufactured by Quiagen), Cobas 4800 HPV (Roche) and Cervista HR HPV (Hologic); another Roche Diagnostics assay, Amplicor HPV, awaits approval.

These HPV assays use distinct methods to assess DNA of various HPV strains.

There’s a lot of jargon here, and I have to admit some of this was new to me despite my nearly-due diligence as a patient at the gynecologist’s office and my familiarity as an oncologist with the staging, clinical manifestations and treatment of cervical cancer. Who knew so many decisions were made during a routine pelvic exam about which manner of screening?

The main points I took away from this paper:

1. Liquid-based cytology is similar to conventional Pap smear cytology for detecting high-grade dysplasia (abnormal cells) and cervical cancer.

2. It seems that at some medical centers, and possibly overall, there’s a lower proportion of inadequate cell specimens when practitioners skip the slides and use the liquid method. This means that fewer women need be called back for another procedure.

3. Finding HPV sequences in the cervix yields many false positives, in terms of malignancy.

The researchers conclude that further studies are needed to sort out how HPV testing can improve or supplement cervical cancer screening. The main limitation is that many young women are infected with potentially cancer-causing strains of HPV, but most don’t get cervical cancer. When cervical cancer does develop that’s usually later on, a decade or longer after the relevant viral infection.

The second Annals article, a helpful narrative review, considers the practical implications of the above findings. The authors state that over 40 types of HPV can infect the cervix. They review that progression to cancer occurs along these 4 steps: HPV transmission, acute infection, persistent infection causing precancerous changes and eventually, in a subset of those infected, invasive cervical cancer.

Figure 1 is remarkably clear:

Prevalence of high-risk HPV and incident cases of cervical cancer in the U.S., 2003–2005. Surveillance Epidemiology and End Results (SEER) data for incident cases among females aged 15 to 19 years and 50 to 64 years.

The graph shows that the prevalence of HPV infection is highest among teens and women in their early 20s, and decreases in older women. By contrast, the incidence of cervical cancer rises steadily in women over 30 years and remains elevated among women in their 40s. The authors show, separately, that the rate of cervical cancer in older women is low.

The central point is that high-risk HPV infection and associated inflammation of the cervix are common in young women, but cervical cancer is rare among those under 30 years. The investigators conclude that cervical cancer screening in women younger than 20 years may be harmful. They also state that evidence supports discontinuation of cervical cancer screening in most women who are over 65 years old.

Two asides on this otherwise non-bloggy topic –

It’s great that the Annals provides the full text of these papers open-access, free of charge to the public.

Amazing how well-accepted is the concept of some viruses causing cancer, today. This was a heretical idea 25 years ago in academic medicine; now it’s dogma.

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‘Cutting For Stone,’ and Considering the Experience of Practicing Medicine

A short note on Cutting for Stone, a novel I’ve just read by Dr. Abraham Verghese. He’s an expert clinician and professor at Stanford. The author uses rich language to detail aspects of Ethiopian history, medicine and quirks of human nature. The book’s a bit long but a page-turner, like some lives, taking a strange and sometimes unexpected course.

For today I thought I’d mention one passage that haunts me. It appears early on, when the protagonist, a man in middle age reflects on his life and why he became a physician:

My intent wasn’t to save the world as much as to heal myself. Few doctors will admit this, certainly not young ones, but subconsciously, in entering the profession, we must believe that ministering to others will heal our woundedness. And it can. But it can also deepen the wound.

The point is, a physician may be immersed in his work in a manner that he is, in effect, “addicted” to practicing medicine – a term Verghese uses later on in the book. There’s an emotional boost, or relief, some doctors glean by their daily tasks. An example he gives is a surgeon who feels better upon seeing his patient, who’d been sick, recovering nicely after an operation. This applies in other fields, including oncology.

I get this. It’s an under-discussed aspect of being a doctor, articulated well in some characters’ pathology and passion.

More on this, later, elsewhere –

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Final Word on Avastin, and Why We Need Better Physicians

Today’s breaking breast cancer news is on Avastin. The FDA has just announced, formally, that it will rescind approval for the drug’s use in people with metastatic breast cancer. Commissioner Dr. Margaret Hamburg writes this her statement:

I know I speak on behalf of the many physicians that have been involved with this issue here at the Food and Drug Administration and elsewhere in saying that we encourage patients, and those who support them, to ask hard questions and demand explanations concerning the drugs that are recommended to treat serious illnesses.

On this much I agree with Dr. Hamburg – that patients and others, including doctors who prescribe treatments to patients with likely incurable illnesses, and all medical conditions, for that matter, should ask hard questions.

Others have already, immediately expressed that the FDA did the right thing. Because they think the FDA’s decision was rational, and it was. Likely there’ll be an editorial in the paper I usually read, celebrating the victory of reason over anecdote. The WSJ, whose words tend to align more with business interests, will likely be critical. Opponents of health care reform will, inappropriately and mistakenly, use this as an example of rationing, which it isn’t.

The fact is that many, and possibly most, medical treatments are given in the absence of studies to justify their use. So you might ask, instead, why give chemotherapy to most stage IV cancer patients. Or why give it in the adjuvant setting? Apart from some tumors, like some kinds of lymphoma and leukemia, and common breast and testicular cancers, and a few others, when carefully measured the benefit is often slim.

What I think is that Avastin is a scapegoat of sorts, a costly drug not particularly worse than many others, nor better, and that helps a small minority of women with a lethal disease for reasons their doctors can’t predict or explain.

We experiment, on insurance and Medicare dollars, with so many costly treatments. Bone marrow transplants, at a cost of hundreds of thousands of dollars per patient, for example, are given to some with little formal proof of benefit for the approved indications. But there’s a lobby for these treatments. Support comes from hospitals profiting from transplant procedures and, more subtly, from academic physicians who’ve built careers in that field and write papers about their benefits, complications and management. I might cite other complex, costly and unproved examples in oncology, surgery and other fields of medicine, but that’s not the real point for today.

What I wonder is, ironically, because the data on Avastin were collected so carefully, that its lack of effectiveness over a population of women was better-documented than has been the lack of evidence for other drugs and regimens. Besides, there’s no group of hospitals and doctors whose profit and livelihood, respectively, depends on giving Avastin to just a few people with metastatic breast cancer. There was just Genentech, an easy big-Pharma target, and a few women, pleading for continued access to a drug that’s helped to keep them alive.

(I wonder, also, had those patients who testified been men, would their words have been taken more seriously?)

Meanwhile, doctors can keep giving Avastin to patients with other forms of cancer, for which its efficacy is not so different as you might think. Like any drug, this drug’s response varies from patient to patient for every tumor type that it might be given. And the physicians can still give Avastin, as the commissioner points out in her decision, to women who can pay for it, by circumstances of their particular insurance, or good fortune of wealth. But some of these women’s families will be hurt hard by this FDA decision. Most are in the 99%.

And so maybe what we really need are better doctors, not only in oncology, who would carefully monitor patients when they give any and every medical treatment and stop it if it’s not working, and continue only if it helps, and would communicate and obtain informed consent through meaningful discourse.

If we had that, we’d save a lot of money, and get better care.

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President Obama Talks About Smoking and Tobacco

Today’s ML comes straight from the Oval Office. President Obama talks about smoking, and how hard it is to stop, and what can be done to reduce the use and long-term health consequences of tobacco.

What I like about this Presidential health advisory:

He credits the ACS, which is sponsoring a smokeout today.

He’s clear about the problem’s scope: “Today 46 million Americans are still hooked, and tobacco remains the leading cause of preventable, early deaths in this country.”

He doesn’t deny his own history. His experience lends credibility to his words; he understands how hard it is to stop smoking once you’ve begun.

He considers a solution: “We also know that the best way to prevent the health problems that come from smoking is to keep young people from starting in the first place.”

He reflects on the power of tobacco companies, which are fighting requirements for candid warning labels on their products.

All in 1 minute and 34 seconds!

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iPod Therapy – Why Not Prescribe It?

Yours truly, the author of Medical Lessons, is listening to music while she writes. A live version of the Stones’ “Silver Train” has just come on, and she’s happily reminded of something that happened 30 years ago. Distracting? Yes. Calming? Yes. Paradoxically helps to keep me on track? Yes.

My iPod keeps my mind from wandering further. And it lifts my mood.

And so here, on my blog, which is not peer-reviewed or anything like that, I put forth the medical concept of “iPod therapy.”

“When you’re weary, feeling small…” Music can help.

Today’s news reports that 1 in 5 Americans take drugs for psychiatric conditions. That sounds like a lot to me, but I’m no pharmaceutical surveyor. Of course many people need and benefit from medical help for depression and other mental illnesses.

But, in all seriousness, I wonder how many people might use music like a drug to keep them relaxed, happy, alert…

Why not prescribe music? It works for me, n=1.

Maybe doctors should be recommending iPods, or radios, or Pandora to some of their patients who are feeling down. I hope an academic psychiatrist somewhere, without ties to Apple or Pandora or Bose or other relevant party is coordinating a careful, prospective study of this promising and relatively inexpensive intervention.

As best I can tell, music is non-addictive. Except that if I had to live without it, I’d start humming, or maybe singing, which might be detrimental to those who live near.

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Thoughts, on Getting My Photo Taken at a Medical Appointment

A funny thing happened at my doctor’s appointment on Friday. I checked in, and after confirming that my address and insurance hadn’t changed since last year, waited for approximately 10 minutes. A worker of some sort, likely a med-tech, called me to “take my vitals.”

She took my blood pressure with a cuff that made my germ-phobic self run for self-regulation, i.e. I stayed quiet and didn’t express my concern about the fact that it looked like it hadn’t been washed in years. I value this doctor among others in my care, and I didn’t want to complain about anything. Then the woman took my weight. And then she asked if she could take my picture, “for the hospital record.”

I couldn’t contain my wondering self. “What is the purpose of the picture?” I asked.

“It’s for the record,” she explained. “For security.”

I thought about it. My picture is pretty much public domain at this point in my life, a decision I made upon deciding not to blog anonymously. Besides, most everyone at the medical center used to know me, including the receptionists, janitors, cafeteria cashiers, nurses’ aides, social workers, deans, full professors, geneticists, fellows in surgery and old-time voluntary physicians, among others who work there. So why didn’t I want this unidentified woman who works in my oncologist’s office to take my picture?

It made me uncomfortable, and here’s the reason: My picture is a reminder that, without it, I might be like any other patient in the system. They (administrators?, nurses, other docs, maybe even my future doctors) will need or want the picture to recall and be certain who Elaine Schattner is.

Don’t get me wrong. I agreed to the photo after all of maybe 20 seconds deliberating. (And my doctor was, I soon learned, duly informed I’d “had an issue” with it. Was that for just asking the reason?) The unidentified med-tech person used an oddly small, ordinary pink camera to complete her task.

When I met with my doctor, she explained that the photo is for security and, essentially, to reduce the likelihood of errors. The hospital has records of so many thousands of patients, many who have similar or identical names. There are good reasons to make sure that your notes on “Sally Smith” are entered into the chart of “Sally Smith” who is your patient.

It’s understandable. I remember when at the nurses’ station there’d be a sign (on “our” side) saying something like “CAREFUL: Anna Gonzalez in 202, Alma Gonzalez in 204b,” or something like that.

Patients blur.

It’s hard, veritably impossible, for most doctors and nurses to keep mental track of all of the patients they’ve ever seen and examined. There’s utility in the new system. Yes, it’s a good idea for a doctor, say upon receiving a call from a woman she hasn’t seen in 3 or 6 or 9 years, to see her picture in the chart, as a reminder.

But I hope my doctors know who I am, and not just what I look like in the image.

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Magic Johnson is Alive 20 Years after Announcing He Had HIV

Yesterday’s Washington Post Sports has a clip from CNN, 20 years ago, when basketball star Magic Johnson announced on TV that he had HIV, the virus that causes AIDS. The date was Nov 7, 1991.

“Where were you when Magic made his announcement? What were your thoughts on Johnson and HIV/AIDS that day and how have they changed?” asks Matt Brooks in his column.

I can’t quite recall where I was. Probably I was at the hospital working, possibly even taking care of a patient with HIV. But I do remember thinking how much courage it must have taken for him to come out with it.

He understood, likely, that he would die soon, and his doctors probably thought the same. There were only two antiviral drugs approved for HIV back then. There was so much stigma, and fear.

Today you can see and listen to him in an interview on ESPN.

It’s great to see Magic Johnson back in the news, even if it’s (just) in a sports sections, and to be reminded that he’s alive, doing OK. The condition we thought was a death sentence has become a chronic illness, with so many drugs available for treatment it’s hard to keep track.

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Visiting the Scar Project Exhibit

On Friday I visited the Scar Project exhibit at Openhouse, on Mulberry Street just south of Spring. Photographer David Jay offers penetrating, large, wall-mounted images of young people with breast cancer.

The photos reveal women who’ve have had surgery, radiation, reconstruction or partial reconstruction of the breasts. Some are strikingly beautiful. Some appear confused, others confident. Some look right at you, defiant or maybe proud. Some, post-mastectomy, adopt frankly or strangely sexual postures. Others hide a breast, or turn away from the lens.

This collection is not for everyone. The photos of ravaged bodies of women with cancer might be upsetting, if not frankly disturbing, to some who look at them. Not everyone chooses to do so.

The women’s scars and expressions are telling. Though not representative, these images reflect wounds not often-shown in medical journals, or elsewhere.

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On Alcohol and Breast Cancer, Guilt, Correlations, Fun, Moderation, Doctors’ Habits, Advice and Herbal Tea

Few BC news items irk some women I know more than those linking alcohol consumption to the Disease. Joy-draining results like those reported this week serve up a double-whammy of guilt: first – that you might have developed cancer because you drank a bit, or a lot, or however much defines more than you should have imbibed; and second – now that you’ve had BC, the results dictate, or suggest at least, it’s best not to drink alcohol.

The problem is this: If you’ve had BC and might enjoy a glass of wine, or a margarita or two at a party, or a glass of whiskey, straight, at a bar, or after work with colleagues, or when you’re alone with your cat, for example, you might end up feeling really bad about it – worse than if you had only to worry about the usual stuff like liver disease and brain damage, or if you could simply experience pleasure like others, as they choose.

The newly-published correlative data, in the Nov 2 issue of JAMA, are clear. The findings, an offshoot of the Nurses’ Health Study, involve over 105,000 women monitored from 1980 until 2008. The bottom line is that even low levels of alcohol consumption, the equivalent to 3-6 drinks per week, are associated with a statistically significant but slight increase in breast cancer incidence. And the more a woman drinks, the more likely she is to develop breast cancer.

All things considered, it might be true that alcohol is a breast carcinogen, as Dr. Steven Narod calls it in the editorial accompanying the research study. Still, there’s no proof of cause and effect: Other factors, like consuming lots of food or perhaps some yet-unidentified particularity about living in communities with abundant food and alcohol, are potential co-variables in this story. But what if it is true?

From the editorial:

These findings raise an important clinical question: should postmenopausal women stop drinking to reduce their risk of breast cancer? For some women the increase in risk of breast cancer may be considered substantial enough that cessation would seem prudent. However, there are no data to provide assurance that giving up alcohol will reduce breast cancer risk.

How I see it is this: Everything’s best in moderation, including enjoyment of one’s life. You work, you rest, you have some fun.

This evidence is not like the strong data linking cigarettes to smoking that officials sat on for a few decades under the influence of the tobacco industry. This is a plausible, mild, and at this point well-documented correlation.

I don’t deny the sometimes harmful effects of alcohol; no sane physician or educated person could. But if you have a glass of wine, or even a second, so long as you don’t drive a car or work while affected, I don’t see it as anyone’s business but your own. More generally, I worry about how much judging there is by people who behave imperfectly, and how that can make individuals who are good people in most ways feel like they don’t deserve to be happy or enjoy their lives.

Women, in my experience, are generally more vulnerable to the put-downs of others. And so my concern about the BC-alcohol link is that this will, somehow, be used, or have the effect of, making survivors or thrivers or women who haven’t even had breast cancer feel like they’re doing the wrong thing if they go to a party and have a drink. And then they’ll feel badly about themselves.

Really I’m not sure what more to say on this loaded topic, except that it points to the deeper and broader ethical dilemma of doctors who are not all perfect examples of moderation, expecting and asking other people to change their personal habits when they themselves like to go out and have fun, and drink, at parties, or have wine in the evenings over dinner in the privacy of their homes.

How shall I resolve this post?

Last night I sipped Sleepytime tea, manufactured by Celestial Seasonings, before reading a book. The stuff is said to be 100% natural, with “a soothing blend of chamomile, spearmint and lemongrass.” I tried it first a few weeks ago and, by a placebo effect or through real chemistry, it helps me sleep more soundly.

I’ve absolutely no idea what are the effects of “Sleepytime tea” on breast cancer. It might help, it might hurt, or it might do nothing at all.

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A Poster for Healthy Eating, 1940s Style

A curious diagram appeared in the most recent NEJM, in a perspective on U.S. dietary guidelines. It’s a USDA food wheel from the early 1940s. With Twitter-like style, it says: “For Health…eat some food from each group…every day!

The details are rich: “butter and fortified margarine” constitute 1of the 7 groups. Further inspection-worthy, IMO.

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