Letters to the Editor

Procedural Advice for Performing Anal Pap Smears

TO THE EDITOR: Thank you for your article, "Health Care Screening for Men Who Have Sex with Men.”1 Several months ago I had a man come to my office whose chief complaint was: "I guess it's time for me to have a Pap smear.” I was clueless, and actually unable to grant his request that day. I appreciate American Family Physician publishing this article,1 as I know this may be considered murky territory by many physicians.

I have several questions: (1) How does one collect an anal Pap smear? (2) Do we use a wet cotton swab? (3) How far should the cotton swab be inserted? (4) Do we use the ThinPrep container or do we prepare an old-fashioned slide? (5) Should we also be ordering human papillomavirus screening as we do for female patients?

I was unable to find someone at my teaching institution who was able to answer my questions. I would appreciate any guidance.

ELIZABETH NEWMAN, M.D.

Burlington, VT

REFERENCE

1. Knight D. Health care screening for men who have sex with men. Am Fam Physician 2004;69:2149-56.

IN REPLY: Anal Pap smears are important to consider in men who have sex with men, especially those who are human immunodeficiency virus (HIV)-positive. Anal Pap smears also should be considered in men and women with a history of anogenital human papillomavirus (HPV) infection, anal receptive intercourse, multiple sexual partners, and a history of sexually transmitted disease or anal condyloma.1

The incidence of squamous cell carcinoma (SCC) of the anus in men who have sex with men is estimated to be 35 per 100,000.1 It is approximately the same incidence as that of SCC of the uterine cervix before the institution of screening programs using Pap smears. Carcinoma of the anus now represents about 1.5 percent of all cancers of the digestive tract. The American Cancer Society estimated that 4,010 new cases would be diagnosed in the United States in 2004, an increase from 3,400 cases in 2000. Approximately 620 patients will die of the disease this year.2

Anal cytology, when atypical squamous cells of undetermined significance (ASCUS) is included as an abnormal cytologic result, has 69 percent sensitivity in HIV-positive men and 47 percent in HIV-negative men. However, cost-effectiveness modeling has resulted in anal Pap smears being cost-effective if performed in HIV-positive men every year and in HIV-negative men every three years.3

The sampling for anal Pap smears is easy to accomplish. A Dacron cotton swab should be used. Avoid using a cotton swab on a wooden stick, because these often break and will splinter. The patient may be placed in the lateral recumbent position. In women, the dorsal lithotomy position may be used as when completing a cervical Pap smear. The Dacron swab is inserted 5 to 6 cm without direct visualization. Firm lateral pressure is applied to the swab handle. It is rotated and slowly withdrawn from the anal canal.1 Make sure to sample the transition zone during removal, as this area, which separates the columnar epithelium of the rectum from the keratinizing anal squamous mucosa, is the site where most anal intraepithelial neoplasms arise.2

Liquid cytology is the preferred method for preservation. This eliminates artifact with drying and reduces the amount of fecal material and bacteria that can obscure cellular detail. However, air-drying and fixation may be used if liquid cytology is not available.

Criteria used to interpret HPV-related lesions of the anus and cervix are essentially the same. Coexisting infections also may be noted.1 These include herpes virus and cytomegalovirus infections and Candida. Other organisms such as amebic cysts, trophozoites, pinworm eggs, and strongyloides have been seen. Any report of ASCUS or higher on anorectal cytology requires an anal colposcopy. These are easily accomplished using an anoscope and a colposcope.

The question of testing for HPV has not been answered thoroughly.1 Rates of HPV positivity are high in the populations targeted for screening using anorectal cytology. The technology used for cervical samples has not been approved by the U.S. Food and Drug Administration for use in anorectal cytology. However, HPV testing does have a good negative predictive value.1

DANIEL KNIGHT, M.D.

University of Arkansas for Medical Sciences
4301 W. Markham, Slot 530
Little Rock, AR 72205

REFERENCES

Atomoxetine in the Treatment of Patients with ADHD

TO THE EDITOR: In a STEPS review, Dr. Lynch1 states: "Given safety concerns (growth retardation, potential adverse effects in slow metabolizers) and its high cost, atomoxetine (Strattera) should be considered only as an alternative for patients who are intolerant or unresponsive to stimulant medications.” However, in our opinion, these claims are not supported by the data.

Atomoxetine is the first and only non-controlled medication to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention-deficit/hyperactivity disorder (ADHD). In the first year after its FDA approval, more than 1 million patients were treated with Strattera. In a randomized, double-blind, placebo-controlled study2 to assess potential abuse in adult patients, Strattera was not associated with a pattern of response that suggested stimulant or euphoriant properties. Strattera does not have a black box warning regarding the potential for abuse, unlike other medications used to treat ADHD.3

After starting Strattera, some patients initially may lose a small amount of weight (approximately 1.1. lbs [0.5 kg]). But in patients treated for at least 18 months, weight gain resumes and appears to follow a normal pattern during longer-term treatment. Preliminary findings indicate that Strattera is unlikely to have marked effects on juvenile growth or final adult height.4 Existing stimulant treatments for ADHD have been shown to slow growth and weight gain in children. At this time, there have been no head-to-head studies to compare the impact of Strattera and stimulants on growth. There is no need to adjust the dosage of Strattera based on genotype or to perform genetic testing before beginning treatment.

The FDA has closely examined the extensive research data on Strattera and has judged it to be a safe and efficacious agent for the treatment of ADHD in children, adolescents, and adults. At this time, it is the only FDA-approved treatment for ADHD in adults. Based on the safety and efficacy profiles of Strattera, it should be considered a valuable agent in the initial and maintenance treatment of patients with ADHD.

JAN A. GERBERS, PHARM.D.

ALBERT J. ALLEN, PH.D.

Eli Lilly and Company
Indianapolis, IN 46285

REFERENCES

editor's note: Eli Lilly and Company manufactures Strattera.

in reply: As Drs. Gerber and Allen note, the STEPS review1 of atomoxetine (Strattera) was published in 2003 and relied on data published almost two years ago.1 All published trials available at the time that piece was written evaluated the efficacy and safety of atomoxetine for up to only 10 weeks. My concerns about the long-term safety of this important new drug for attention-deficit/hyperactivity disorder (ADHD) were based on data that were then available.

Drs. Gerbers and Allen provide new information that "in patients treated for at least 18 months, weight gain resumes and appears to follow a normal pattern.” They reference a meeting presentation,2 which I could not find in abstract form or in a publication. However, several of the same authors recently have reported the results of a trial evaluating atomoxetine treatment for one year in children with ADHD.3 Weight percentile decreased from 52.3 to 48.4 in those receiving atomoxetine, while it increased in the placebo group from 53.1 to 58.5 (P < .001). Similarly, height percentile decreased from 56.1 to 53.4 in those receiving atomoxetine and increased in the placebo group from 59.9 to 60.6 (P < .001).

The latest revision of the package insert for Strattera states under the warnings section, "there are no long-term, placebo-controlled data to evaluate the effect of Strattera on growth,” and "patients requiring long-term therapy should be monitored and consideration should be given to interrupting therapy in patients who are not growing or gaining weight satisfactorily.”4 If new data are indeed available, I urge the authors to submit these data to the U.S. Food and Drug Administration (FDA) and publish the results in a peer-reviewed journal.

The authors state, "there is no need to adjust the dosage of Strattera based on genotype or to perform genetic testing before beginning treatment.” The FDA does state, "routine laboratory tests are not required.”4 However, once genotyping tests become more available and affordable to the general public, it seems worthwhile to identify patients who are at higher risk for adverse effects. Under precautions, the package insert states: "Poor metabolizers (PMs) of CYP2D6 have a 10-fold higher AUC [area under the curve] and 5-fold higher peak concentration to a given dose of Strattera compared with extensive metabolizers (EMs). Approximately 7 [percent] of a Caucasian population are PMs. Laboratory tests are available to identify CYP2D6 PMs. The blood levels in PMs are similar to those attained by taking strong inhibitors of CYP2D6. The higher blood levels in PMs lead to a higher rate of some adverse effects of Strattera.”4 It also states, "Dosage adjustment of Strattera may be necessary when coadministered with CYP2D6 inhibitors, e.g., paroxetine, fluoxetine, and quinidine.”4

The authors did not mention one new piece of information released by the FDA concerning the safety of atomoxetine. Since their letter was submitted, the package insert was updated in December 2004 with a bolded warning about the potential for severe liver injury and the recommendation that tests should be performed on the first symptom or sign of liver dysfunction.4

Tom Lynch, Pharm.D.

Virginia Commonwealth University, and
Eastern Virginia Medical School
721 Fairfax Ave.
Norfolk, Va. 23507-1912

REFERENCES

1. Lynch T. Atomoxetine for ADHD [STEPS]. Am Fam Physician 2003;68:1827-8.

2. Michelson D, Spencer T, Ruff D, Feldman P. Long-term effects of atomoxetine on growth in children with ADHD. Paper presented at: 51st meeting of the American Academy of Child and Adolescent Psychiatry; October 22, 2003; Miami Beach, Fla.

3. Michelson D, Buitelaar JK, Danckaerts M, Gillberg C, Spencer TJ, Zuddas A, et al. Relapse prevention in pediatric patients with ADHD treated with atomoxetine: a randomized, double-blind, placebo-controlled study. J Am Acad Child Adolesc Psychiatry 2004;43:896-904.

4. Atomoxetine (Strattera). Package insert. Indianapolis, Ind.: Eli Lilly and Company, 2004. Accessed online February 25, 2005, at: http://pi.lilly.com/us/strattera-pi.pdf.

Send letters to Jay Siwek, M.D., Editor, American Family Physician, 11400 Tomahawk Creek Pkwy., Leawood, KS 66211-2672; fax: 913-906-6080; e-mail: afplet@aafp.org.

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