Report of an expert panel for the National Institutes of Health

ACOG CL1 Volume

Report

of an Expert

lthough much is known about the ‘ncidence, etiology, and treatment of cervical cancer, many issues remain unresolved. It is well recognized that invasive carcinoma of the cervix is, in theory, a preventable disease. Modification of high-risk behavior in young people could change the pattern of human papillomavirus (HPV) infection, and research in this area is warranted. Additional research is needed to determine the optimal methods of evaluating and treating human immunodeficiency virus (HIV) -positive women with preinvasive and invasive 1

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Malpractice Infant Morbidity 81 VBAC CVS or Amniocentesis Breech Deliveries Impact of Diabetes Cerebral Palsy & Prematurity BMI, Early BP, & Preeclampsia Necessity of Hematocrit Managing Preterm Labor Cerebral Palsy & Complications

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lesions of the cervix. Improving screening in populations that typically are underscreened, sui:h as the elderly, ethnic minorities, and the poor, will require research direcl:ed toward overcoming the barriers specific to each group. Support should be given to research on provider behaviors that influence patient and clinician compliance with Papanicolaou smear screening. Additional research into methods of improving the accuracy and interpretation of’ cytologic sampling techniques, including liquidbased systems and computer automation, should be encoc.raged.

l Decisions About HRT . Pelvic Floor After Delivery l

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GYNECOLOGY . Menorrhagia TX . Sports 81 Pelvic Damage . Basal Cell Vulvar Carcjnoma l Perfecting the Pap l Vulvar Cancer &Age l Pap Screening Failure

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01998 by the AmericanCollege01Obsletrlc~ansand Gynecaloglsls Publtshedby EisewerScwce Inc 1085.6662/98/$5.50

of Health

There are large numbers of women with Papanicolaou smears showing squamous intraepithelial lesion (SIL) each year. The minority of these women will progress to invasive cancer, and it would be advantageous to develop predictive markers to identify those women. This would allow lowrisk women to avoid costly and potentially morbid diagnostic and therapeutic procedures. Additional research to identify molecular, pathologic, and immunologic markers that would assist in this triage is needed. Clinical trials, including the atypical squamous cells of undetermined significance and low-grade SIL trial, deserve support. In women with invasive cancer of the cervix, a number of key issues merit further investigation. Research into the role of modern radiologic imaging (computed tomography, magnetic resonance imaging, ultrasound, positron emission tomography) in determination of tumor volume and

. Ca Channel Blockers t< Cancer . NSAIDs & Gastropathy l Cigarettes, BMI, & I+ctures . Herpes on the Rise . HRT &Acute MI l Circumcision Anesthe!la . Hyperrension Guidelines . HRT Rr Stroke . Journal Reference Accuracy

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LETTERS

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HISTORICAL PERSPECWE

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From the Department of He&h and Human Services, US Public Health Service, Bethesda, Matyland. *This is the flnaI installment of a four-part series. Parts l-3 have been published in previous issues of the ACOG C&ticalRcvim. A copy of the entire document may be obtained by calling (888) 644-2667 or by visiting the following Web site: http://consensus.nih.gov. Thlc document IS an independent report of the panel and is not a policy statement of thr National Institutes of Health or the Federal Government.

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ACOG CLINICAL REVIEW Ralph W. Hale, MD Editor John J. Graham, MD Larry I’. Griffin, MD Gerald B. Holzman, MD Luella Klein, MD Stanley Zinberg, MD Associate Editors . . .

Acta Obstetricia et Gynecologica Scandinavica American

Journal of Obstetrics and Gynecology

Annals

of Internal

Medicine

Australian and New Zealand Journal of Obstetrics and Gynaecology British

Journal of Obstetrics and Gynaecology

Fertility and Sterility Lancet New

England Obpetrics

Journal

of Medicine

and Gynecology . . .

Co right 0 1998by theAmenan Colkgc ofObsrcrricians ul~Gynccol~, Publishedby Elwier Science Inr bimonrhlybyEi&cr SciC~ECInc., 655 Awuc of the Americas, NW York, NY 10010.Suhscripdonprim per yew: For customersin Euqe, the CIS and Japan:insrirurionalrare: NLG 285.W. paonll rate: NLG 153.00, srudcndmidcnr rare: NLG 42.00. For customers in all other counties: lnrtiturionll race:USS 164.00.persoonal rare: LJSI 88.00, studcndrcsidcnr nrc: US0 24.00.Prim includepostageandarc subject co changewithout notice.For additionalinformaion, conuct Elxvicr ScienceCurtomcr S;lppo’[ Dcpmmcnt, P.O. Box 945, NW York, NY 10010, c: (2121633-3730.Tall free (for customersin North America): I-888.4ESlNFO. Fax: (212) 633.3680, E-mail: winf&?&cvier.com. Ad-

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extent of disease is warranted. This imaging information also could be incorporated into radiotherapeutic treatment planning. For those patients with microinvasive adenocarcinema, an acceptable definition and guidelines for selecting patients for fertility-preserving treatment are needed. Additional information to identify those patients with microinvasive squamous cancer who can be treated safely with conservative, fertility-sparing surgery also is indicated. Development of methods to improve the traditional modalities of surgery and radiation therapy in the treatment of cervical cancer is an important area of research. The advent of newer laparoscopic procedures offers the potential for a relatively nonmorbid histopathologic staging technique of pelvic and para-aortic lymph nodes. The status of these lymph nodes determined either laparoscopically or by other methods is one of the most important prognostic indicators, and pretreatment knowledge of lymphnode status could allow for a more rational allocation of patients into therapeutic groups. Prospective trials evaluating the usefulness of histopathologic lymph-node staging are indicated. Studies are needed to assess quaIity-of-life issues in patients undergoing therapy for preinvasive and invasive lesions of the cervix. In patients with low-grade SIL, studies regarding the impact of follow-up only versus active intervention are needed. The impact of frequent follow-up visits and the uncertainty of receiving no treatment for a preinvasive lesion with an unknown natural history may be significant and should be studied. Data also are needed regarding quality-of-life issues related to the selection of radical hysterectomy versus definitive radiation treatment in patients with early invasive cervical cancer. The optimal role for chemotherapy in the treatment of early or advanced invasive cervical cancer is unknown. In the area of concomitant chemotherapy and radiation, a number of clinical trials have been completed or are under way, but at this time there is no proven benefit to combining chemotherapy with radiation. Additional studies are war1998

ranted, including quality-of-life studies. Several issues related to radiation therapy for cervical cancer need to be addressed. Evaluation of the impact of ~53 status and HPV subtypes on radiation responsiveness is a promising area of research that may allow optimization of treatment strategies. Dose/response relationships, time/ dose relationships, improvements in technical instrumentation, and optimization of brachytherapy techniques need further study. Predictive assays for tumor and normal tissue radiation sensitivity would allow for individualization of radiation prescriptions, whereas addressing the influence of hypoxia and anemia could improve the radiation responsiveness of the tumor. Studies in these areas are ongoing and should be supported. Support also should be given to research to develop topical microbitides designed to prevent HPV infection as well as HIV infection and other sexually transmitted diseases. One of the most exciting areas of research in the prevention and treatment of cervical cancer is the development and testing of prophylactic and therapeutic vaccines against HPV. The firmly established causal relationship between HPV infection and cervical neoplasia makes vaccine strategies uniquely appealing as a prophylactic and therapeutic approach. Research efforts in this area should be given the highest priority.

CONCLUSIONS Carcinoma of the cervix is a substantial public health issue worldwide and remains an important issue for women’s health in the United States, especially when one considers the totality of invasive disease and its precursor lesions. The evidence presented at this Consensus Development Conference has led to the following conclusions: l Carcinoma of the cervix is causally related to infection with HPV. Reducing the rate of HPV infection by encouraging changes in the sexual behavior of young people and developing an effective HPV vaccine would reduce the incidence of this disease. Continued

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01998 by the AmericanCollegeof Obstetriciansand Gynecologtsts Pubbshedby ElsewerScienceInc 1085-6862/98/$5.50

4). The relative risk for suspected macrosomic infants was 6.7. The excess cost of performing 250 cesarean deliveries is about $500,000 assuming that the differential between a vaginal delivery and cesarean is about $2000. The award for a successfully litigated birth injury case is more than $l,OOO,OOO (the California limit for pain and suffering is $250,000). So merely on a dollarfor-dollar basis, it is cheaper to perform the operation. This comparison should not stop there, however, as there are more intangible costs to the aggrieved victims, both the injured and the injured’s family, and to the obstetrician undergoing litigation. The lost income suffered by the obstetrician, even if the case is defended successfully, represents many tens of thousands of dollars as the court case drags on. The humiliation of having to report the award to the National Data Bank and having the full dollar amount published on the internet by the California Medical Board (a requirement in this state) at a site that is accessible by

any yahoo with a computer is exposure that no one wishes. Additionally, if the choice is left to most women, quoting the statistic you have provided, I assure you that most mothers would choose cesarean delivery in a heartbeat rather than place a one in 250 risk of permanent neurologic crippling of their child. Although it is possible indeed that some dystocias are unpredictable and unpreventable, the exposure faced by well-intentioned obstetricians and the crippling result to the victims are not served by the cavalier attitude of only one in 250. After all, one in 250 is the very breakpoint offered to women by the California Genetics Program for amniocentesis for karyotypic aneuplodies, a procedure that can disrupt the pregnancy itself. The majority of these women opt for invasive testing to avoid bearing children with handicap.

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Screening with the Papanicolaou smear remains the best available method of reducing the incidence and mortality of invasive cervical cancer. Inability of women to adhere to screening guidelines and failure of many health care providers to recommend screening to their patients are issues that need to be studied further and remedied. Specific attention should be paid to populations known to be underscreened, including the elderly, the uninsured, ethnic minorities-especially Hispanics and blacks-and poor womenparticularly those in rural areas. Women with cervical cancer should have access to appropriate specialists and clinical trials. Microinvasive squamous carcinoma with 53 mm invasion and 57 mm lateral spread (stage IAl) is highly curable with either simple hysterectomy or, in cases in which

01998 by the Amerw,n Collegeof Obstetriciansand Gynecolaglsts PublIshedby ElsevierSctenceInc 1085~6862/98/$5.50

To the Editor: I have found that scoring the uterus with the scalpel and then entering the uterine cavity with a blunt instrument virtually has eliminated fetal laceration at cesarean section in my practice. After using the scalpel to start the incision, I enter the uterus with a pean clamp. I continue the incision bluntly or with scissors if needed. Because I can then see the fetus, it is easier to protect it from laceration. This technique would be useful for residents and when a malpresentation makes laceration more likely. However, in an emergency situation, it may not be feasible. If other physicians have methods to decrease this complication, it would be helpful if they would share them with us.

Steven H. Golde, MD Maternal Fetal Associates Burbank, California

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preservation of fertility is an issue, by cone biopsy with clear margins. Seventy percent to 85% of patients with other stage I and stage IL4 disease are cured. Treatment with radical surgery or radiation is equally effective. Selection criteria for treatment with a particular modality should be established to ensure treatment with one modality or the other, but not both. The combined use of radical surgery followed by radiation increases the cost and morbidity of treatment substantially. Patients with more advanced, nonmetastatic disease are treated with radiation. Although 5-year survival rates in the range of 40 - 60% are reported, there is clearly room for improvement. The addition of systemic chemotherapy in this subset of patients is an active area of investigation. Recurrent cervical cancer confined to the pelvis is treated with the modality that the patient has not received; if the patient has received

Laura Hulbert, MD St. Louis, Missouri Pll S108546621Wx1oo120

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radiation, she is treated with surgery, and vice versa. Radiation may be useful in the palliation of symptoms due to metastases. The efficacy of chemotherapy in those with metastatic disease is best evaluated in the context of a clinical trial. Additional research efforts are needed to improve detection, staging, treatment, and quality of life for cervical cancer patients. Included among these are investigations into optimal pretreatment and post-treatment imaging, improved screening compliance and technical evaluation of Papanicolaou smears, prognostic markers to improve treatment selection, laparoscopic surgical techniques, radiobiology, and systemic chemotherapy. In theory, cervical cancer can be prevented and treated by HPV vaccine therapy; this research holds promise for a profound impact on this disease.

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