Cervical Cancer: New Guidelines for Screening and Prevention
Consensus guidelines for screening and management of abnormal cervical findings have been updated.
In October 2007, evidenced-based guidelines1,2 for the screening and management of cervical cancer were published to replace the 2001 guidelines. The updated guidelines were developed at a 2006 consensus conference of experts representing 29 organizations, including the National Institutes of Health, the American Cancer Society, and the American College of Obstetricians and Gynecologists. Table 1 shows the relevant clinical terms and their abbreviations.
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Table 1. 2006 Consensus Guidelines: Clinical Terms
GUIDELINE OVERVIEW
A significant body of evidence (most notably the results of the National Cancer Institute’s ASC-US/LGSIL triage study) has accrued since 2001 and is central to the new consensus guidelines. The authors make it clear that guidelines cannot apply to all situations and therefore should not serve as a substitute for the clinical judgment that must be used in the management of individual patients. Algorithms for the new recommendations are available from the American Society for Colposcopy and Cervical Pathology.3,4
The 2006 guidelines show significant evolution in the management of abnormal cervical cancer screening results, especially in adolescents and in patients with HGSIL. Minor changes also have been incorporated into management of atypical glandular cells and cervical abnormalities in pregnant patients. The management of LGSIL in most patient categories remains essentially unchanged. Noteworthy revisions have been made in the recommended management of CIN 1. Minor modifications have been made to the CIN 2,3 treatment guidelines, and conservative management recommendations in adolescents have been expanded.
The option of offering HPV testing to women 30 and older, first included in a 2004 interim guideline, has been formally adopted. In women who test negative on Pap smear and positive for HPV, both tests should be repeated in 12 months. When cytology and HPV testing are both negative, routine screening need not be performed for 3 years. HPV testing is recommended for routine screening only in women 30 and older.
UPDATED RECOMMENDATIONS: ABNORMAL CERVICAL CANCER SCREENING TESTS
Adolescent women with AS-CUS or LGSIL:2 Adolescents (women 20 and younger) have a much higher prevalence of HPV than do older women; they also have a higher prevalence of low-grade cervical cytologic abnormalities. Adolescents spontaneously clear most infections, and the associated minor cytologic abnormalities are of little long-term significance. The guidelines do not distinguish between ASC-US and LGSIL in adolescents, as the outcomes of both are similar in this age group.
Reflex HPV testing is not recommended for adolescents with ASC-US. In general, HPV testing is unacceptable in adolescents with ASC-US or LGSIL and, if inadvertently performed, should not influence management. Instead, adolescents with a result of ASC-US or LGSIL should undergo repeat cytologic testing 1 year later. If, at 1-year repeat testing:
Cytology is less than HGSIL, then cytology should be performed again 1 year later. If the second cytologic testing (24 months after the initial finding of ASC-US or LGSIL) reveals ASC-US or greater, then colposcopy should be performed.
Cytology is HGSIL or greater, colposcopy should be performed.
Women with ASC-H: Adolescents as well as adult women with ASC-H should undergo colposcopy.
Immunosuppressed women: ASC-US in immunosuppressed women, such as those with HIV infection, should be managed the same as in women in the general population (i.e., colposcopy is not necessarily required).
Pregnant women with LGSIL: Colposcopy is preferred for nonadolescents, but the procedure may be deferred until 6 weeks postpartum. If colposcopy shows no evidence of CIN 2,3, then postpartum follow-up is recommended.
Postmenopausal women with LGSIL: Postmenopausal women with LGSIL can be managed less aggressively than premenopausal women because the prevalence of HPV positivity in women with LGSIL declines with age. Options include evaluation with reflex HPV testing, repeat cytologic testing at 6 and 12 months, and colposcopy.
Women with HGSIL: New emphasis is placed on the see-and-treat approach in nonadolescent women. Management options include immediate loop electrosurgical excision or colposcopy with endocervical assessment. Loop electrosurgical excision is unacceptable in adolescent women with HGSIL, for whom colposcopy is recommended.
Women with AGC: For all subcategories of AGC and AIS except atypical endometrial cells, the recommendations call for colposcopy with endocervical sampling, HPV testing, and (in women older than 35 or at risk for endometrial hyperplasia) endometrial sampling. In patients with atypical endometrial cells, endometrial and endocervical sampling are appropriate initial steps. If these samples show no endometrial pathology, then colposcopy is recommended.
UPDATED RECOMMENDATIONS: CIN AND AIS
Women with histologic diagnosis of CIN 1:1 Major changes to the recommendations for CIN 1 treatment are focused on the patient’s prior abnormal cytologic findings and not on the adequacy of the colposcopy. Management does not depend on whether the colposcopy was satisfactory, and treatment is not an acceptable option in women with CIN 1 preceded by cytologic evidence of ASC-US, ASC-H, or LGSIL. Rather, follow-up with cytology every 6 to 12 months or HPV testing at 12 months is recommended. If follow-up HPV is positive or follow-up cytology is greater than or equal to ASC-US, then colposcopy is recommended.
In women with CIN 1 preceded by HGSIL or AGC-NOS (not otherwise specified) three options are acceptable: (1) diagnostic excisional procedure (except in adolescents and pregnant women); (2) observation with colposcopy and cytology at 6-month intervals for 1 year if the colposcopy is satisfactory and endocervical sampling is negative; or (3) review of all findings with revised interpretation if necessary.
Adolescents with CIN 1, 2, or 3: Management of adolescents with CIN 1 is not dependent on prior abnormal cytology, and repeat cytology is recommended every 12 months. In adolescents with CIN 2,3, either observation or treatment is acceptable if the colposcopy is satisfactory. If CIN 2 is specified, then observation is preferred. If CIN 3 is specified or if colposcopy is unsatisfactory, treatment is recommended. If CIN 3 is specified and colposcopy is adequate, then repeat colposcopy and cytology at 6-month intervals is acceptable.
Women with CIN 2,3: Either excision or ablation is acceptable in cases with satisfactory colposcopy. When colposcopy is unsatisfactory, a diagnostic excisional procedure is the recommended treatment. In women with recurrent CIN 2,3, a repeat diagnostic excisional procedure is recommended over transitional zone ablation (T zone; junction of squamous and columnar epithelium). For older women with recurrent CIN 2,3 who have concluded childbearing, either repeat diagnostic excision or hysterectomy is an acceptable option.
Adenocarcinoma in situ: Hysterectomy is the preferred treatment, with conservative management acceptable only if preservation of fertility is desired. In such cases (and when margins are involved or the endocervical sampling is positive), reexcision is recommended.
CONCLUSION
Progress in our understanding of the natural history of cervical intraepithelial lesions and HPV infection has led to significant changes in recommendations for evaluation and treatment of abnormal Pap smears, cervical intraepithelial neoplasias, and adenocarcinoma in situ. These advances, in concert with HPV vaccination, show clear promise in preventing cervical cancer.
— Ann J. Davis, MD
Published in Journal Watch Women's Health November 29, 2007
Citation(s):
1. Wright TC Jr et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 2007 Oct; 197:340.
Medline abstract (Free)
2. Wright TC Jr et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007 Oct; 197:346.
Medline abstract (Free)
3. American Society for Colposcopy and Cervical Pathology. Management of women with atypical squamous cells of undetermined significance (ASC-US). 2006, 2007. (http://www.asccp.org/pdfs/consensus/algorithms_cyto_07.pdf)
4. American Society for Colposcopy and Cervical Pathology. Management of women with a histological diagnosis of cervical intraepithelial neoplasia grade 1 (CIN 1) preceded by ASC-US, ASC-H or LSIL cytology. 2006, 2007. (http://www.asccp.org/pdfs/consensus/algorithms_hist_07.pdf)
Friday, December 21, 2007
Thiazolidinediones and Heart Disease Risk
Pioglitazone had a mixed risk profile, and rosiglitazone increased risk for ischemic heart disease, but neither increased mortality.
Results from small clinical trials and early pooled analyses have raised concerns about cardiovascular risks associated with rosiglitazone, one of two thiazolidinediones used to treat patients with type 2 diabetes mellitus. Two new meta-analyses further clarify the risks associated with pioglitazone and rosiglitazone.
Independent researchers analyzed data provided by the manufacturer from 19 randomized trials (16,390 patients) that compared pioglitazone with placebo or an active comparator. Most treatment protocols were 12 to 24 months. The hazard ratios for myocardial infarction, stroke, or death each were reduced after about 1 year of treatment with pioglitazone, although only the 18% reduction in the combined endpoint was significant. Risk for serious heart failure was significantly increased by 41%.
In a review of 140 randomized trials, researchers found 4 trials (14,291 patients) that compared rosiglitazone with placebo or an active comparator and had at least 12 months of follow-up. The risk for myocardial infarction in patients who received rosiglitazone was increased by about 40%, and the risk for heart failure was more than doubled; however, the risk for death from cardiovascular disease was not increased.
Comment: Both thiazolidinediones are associated with increased risk for heart failure in patients with type 2 diabetes mellitus, but only rosiglitazone appears to increase risk for ischemic heart disease. Prescribing information for both drugs now includes a "black box" warning about heart failure; in addition, an FDA advisory committee has suggested that warnings about ischemic heart disease be included for rosiglitazone. Editorialists note how unlikely it would have been for either drug to have been approved initially had these risks been known. They call for tighter postmarketing surveillance, especially for new classes of drugs and in higher-risk patients.
— Thomas L. Schwenk, MD
Results from small clinical trials and early pooled analyses have raised concerns about cardiovascular risks associated with rosiglitazone, one of two thiazolidinediones used to treat patients with type 2 diabetes mellitus. Two new meta-analyses further clarify the risks associated with pioglitazone and rosiglitazone.
Independent researchers analyzed data provided by the manufacturer from 19 randomized trials (16,390 patients) that compared pioglitazone with placebo or an active comparator. Most treatment protocols were 12 to 24 months. The hazard ratios for myocardial infarction, stroke, or death each were reduced after about 1 year of treatment with pioglitazone, although only the 18% reduction in the combined endpoint was significant. Risk for serious heart failure was significantly increased by 41%.
In a review of 140 randomized trials, researchers found 4 trials (14,291 patients) that compared rosiglitazone with placebo or an active comparator and had at least 12 months of follow-up. The risk for myocardial infarction in patients who received rosiglitazone was increased by about 40%, and the risk for heart failure was more than doubled; however, the risk for death from cardiovascular disease was not increased.
Comment: Both thiazolidinediones are associated with increased risk for heart failure in patients with type 2 diabetes mellitus, but only rosiglitazone appears to increase risk for ischemic heart disease. Prescribing information for both drugs now includes a "black box" warning about heart failure; in addition, an FDA advisory committee has suggested that warnings about ischemic heart disease be included for rosiglitazone. Editorialists note how unlikely it would have been for either drug to have been approved initially had these risks been known. They call for tighter postmarketing surveillance, especially for new classes of drugs and in higher-risk patients.
— Thomas L. Schwenk, MD
Raloxifene Approved for Reducing Invasive Breast Cancer Risk
The osteoporosis drug raloxifene (Evista) has been approved for the prevention of invasive breast cancer in postmenopausal women with osteoporosis or postmenopausal women at high risk for invasive breast cancer, the FDA announced Friday.
The agency warned that raloxifene, a selective estrogen receptor modulator, should not be taken with cholestyramine or estrogens. Premenopausal women, especially if they are pregnant or considering pregnancy, also should not take this drug.
Raloxifene can cause serious side effects, including deep venous thrombosis, pulmonary embolism, and death due to stroke. Accordingly, the director of the FDA's Center for Drug Evaluation and Research cautioned that "the benefits and risks of taking [raloxifene] should be carefully evaluated for each individual woman."
The agency warned that raloxifene, a selective estrogen receptor modulator, should not be taken with cholestyramine or estrogens. Premenopausal women, especially if they are pregnant or considering pregnancy, also should not take this drug.
Raloxifene can cause serious side effects, including deep venous thrombosis, pulmonary embolism, and death due to stroke. Accordingly, the director of the FDA's Center for Drug Evaluation and Research cautioned that "the benefits and risks of taking [raloxifene] should be carefully evaluated for each individual woman."
Monday, December 3, 2007
Hypertonic Saline for Bronchiolitis
Nebulized hypertonic saline reduced hospital length of stay in young children with bronchiolitis.
Viral bronchiolitis is a common cause of hospitalization for infants and young children during the winter months, but evidence does not support therapeutic interventions other than supportive care (Journal Watch Pediatrics and Adolescent Medicine Jan 10 2007). Nebulized hypertonic saline (HS) has shown promise in the treatment of small airway obstruction in patients with cystic fibrosis. To evaluate the efficacy of this treatment for viral bronchiolitis, investigators in Canada and the United Arab Emirates randomized 96 children younger than 18 months (mean age, 4.7 months) who were hospitalized with moderately severe bronc hiolitis to receive frequent (every 2–6 hours) doses of either nebulized 3.0% HS or 0.9% normal saline (NS).
Hospital length of stay, the primary outcome, was significantly shorter in the HS group than in the NS group (2.6 vs. 3.5 days). Discharge decisions were based on clinical judgment or protocol-based criteria at the treating clinician’s discretion. The frequency of add-on nonprotocol treatments, given at the attending physician’s discretion, was similar in the two groups; about 60% of nebulizations in both groups included albuterol or racemic epinephrine. No adverse respiratory effects were noted, although two children in the HS group and three in the NS group were withdrawn from the study by parents because of crying or agitation during nebulization.
Comment: Most of the hospitalized infants in this study tested positive for respiratory syncytial virus. Thus, these findings are applicable to typical moderately ill infants with bronchiolitis in the U.S. The nebulization treatments in this study were frequent, every 2 hours at first, but a previous inpatient study that administered nebulizations three times daily reported a similar 1-day reduction in hospital stay. Because most patients in the current study received additional nebulized medications rather than hypertonic saline alone, editorialists propose a future study to explore the possible synergy between HS and bronchodilators.
— Cornelius W. Van Niel, MD
Published in Journal Watch Pediatrics and Adolescent Medicine November 7, 2007
Citation(s):
Kuzik BA et al. Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. J Pediatr 2007 Sep; 151:266.
Medline abstract (Free)
Calogero C and Sly PD. Acute viral bronchiolitis: To treat or not to treat — That is the question. J Pediatr 2007 Sep; 151:235.
Viral bronchiolitis is a common cause of hospitalization for infants and young children during the winter months, but evidence does not support therapeutic interventions other than supportive care (Journal Watch Pediatrics and Adolescent Medicine Jan 10 2007). Nebulized hypertonic saline (HS) has shown promise in the treatment of small airway obstruction in patients with cystic fibrosis. To evaluate the efficacy of this treatment for viral bronchiolitis, investigators in Canada and the United Arab Emirates randomized 96 children younger than 18 months (mean age, 4.7 months) who were hospitalized with moderately severe bronc hiolitis to receive frequent (every 2–6 hours) doses of either nebulized 3.0% HS or 0.9% normal saline (NS).
Hospital length of stay, the primary outcome, was significantly shorter in the HS group than in the NS group (2.6 vs. 3.5 days). Discharge decisions were based on clinical judgment or protocol-based criteria at the treating clinician’s discretion. The frequency of add-on nonprotocol treatments, given at the attending physician’s discretion, was similar in the two groups; about 60% of nebulizations in both groups included albuterol or racemic epinephrine. No adverse respiratory effects were noted, although two children in the HS group and three in the NS group were withdrawn from the study by parents because of crying or agitation during nebulization.
Comment: Most of the hospitalized infants in this study tested positive for respiratory syncytial virus. Thus, these findings are applicable to typical moderately ill infants with bronchiolitis in the U.S. The nebulization treatments in this study were frequent, every 2 hours at first, but a previous inpatient study that administered nebulizations three times daily reported a similar 1-day reduction in hospital stay. Because most patients in the current study received additional nebulized medications rather than hypertonic saline alone, editorialists propose a future study to explore the possible synergy between HS and bronchodilators.
— Cornelius W. Van Niel, MD
Published in Journal Watch Pediatrics and Adolescent Medicine November 7, 2007
Citation(s):
Kuzik BA et al. Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. J Pediatr 2007 Sep; 151:266.
Medline abstract (Free)
Calogero C and Sly PD. Acute viral bronchiolitis: To treat or not to treat — That is the question. J Pediatr 2007 Sep; 151:235.
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