CONFRONTING CERVICAL CANCER

Transcription

1 CONFRONTING CERVICAL CANCER Screening Is the Key to Stopping This Killer

2 Katherine L. Adams, RNC, MSN Cervical cancer may not always be a killer of women, yet it s the third-most common cancer in women worldwide (Follen & Richards-Kortum, 2000). This year, some 13,000 new cases of cervical cancer will be diagnosed in American women, and 4,100 women will die of cervical cancer. Recent changes in the statistical reporting and even in the definition of what composes cervical cancer have complicated the interpretation of data regarding cervical cancer (see Box 1: The Bethesda System 2001 ). Regardless, the classification of cervical cancer as a sexually transmitted disease of a progressive nature, as well as the identification of its most common etiology via human papillomavirus (HPV) infection in the presence of cofactors, is quite consistent in the literature (Cuzick, 2000; Kiviat, 1996; McCance & Huether, 1998; The ALTS Triage Study Group, 2000; Wright, Denny, Kuhn, Pollack, & Lorincz, 2000). New national consensus guidelines recently published in the Journal of the American Medical Association (April 24, 2002) are offering additional guidance to clinicians regarding how to better evaluate women whose Pap tests suggest they may have cervical cancer or abnormal cells that may lead to cervical cancer (see Box 2: National Consensus Guidelines ). Nurses in virtually every clinical setting that involves primary care for women have the opportunity to help reduce the incidence of cervical cancer by promoting annual screening. According to recent estimates, most diagnoses of cervical cancer among American women occur within the 15 percent of women who have not undergone gynecological screening in the previous five years (Levie, 2001). Additionally, nurses play an important role in educating women regarding cervical cancer and HPV risks. Nurses can counsel women who have been identified with risk factors for cervical cancer that are amenable to intervention, such as smoking. It s important for nurses to collaborate with other types of health care providers and to participate in identifying and reducing factors among women that inhibit their willingness and desire for annual gynecological exams and screens. Pathophysiology Cervical cancer begins with abnormal changes in the cellular lining or surface of the cervix. These changes most often develop in the area of the squamous-columnar junction. Here, cylindrically shaped secretory epithelial cells (columnar) from the cervical lining meet the protective flat epithelial cells (squamous) from the outer cervix and

3 Box 1. The Bethesda System 2001 Diagnostic findings regarding cervical cancer are most commonly reported using the Bethesda system, which was initially developed in the late 1980s (Lowdermilk, 2000; Noller, 1996; The ALTS Group, 2000) and updated in December 2001 (Levie, 2001). The Bethesda system is credited with increased reporting regarding cervical cancer as compared to reporting systems previously used (Noller, 1996). Previously, using the Bethesda system, the three broad categories by which epithelial cell abnormalities were reported were atypias or atypical squamous cells of undetermined significance (ASC-US) low-grade squamous intraepithelial lesions (SILs) high-grade squamous intraepithelial lesions HPV-related cervical cell changes are included in the low-grade SIL category as are the mild dysplasia and cervical intraepithelial neoplasia (CIN I) of earlier classification systems (Lowdermilk, 2000, p. 287). The 2001 Bethesda system identifies atypical squamous cells (ASC) as those that demonstrate cytologic changes suggestive of a squamous intraepithelial lesion (SIL) that are quantitatively or qualitatively insufficient for a definitive interpretation (Levie, 2001). Within ASC, two subdivisions have been delineated. Atypical squamous cells of undetermined significance (ASC-US) have been differentiated from atypical squamous cells for which the presence of high-grade SIL (as defined above) cannot be excluded (ASCH) (Levie, 2001). Included in the Bethesda system was the glandular corollary to ASC-US: AGUS, which signified atypical glandular cells of undetermined significance (Levie, 2001). Because of its high association with pathological conditions, some suggested the term is a misnomer (Geier, Wilson, & Creasman, 2001). Bethesda 2001 proposed the term be eliminated and two other categories be added: atypical glandular endocervical cells, favor neoplasia and endocervical adenocarcinoma in situ (Levie, 2001). (continued) Katherine L. Adams, RNC, MSN, is a staff nurse and staff development coordinator at Lakewood Hospital in Lakewood, OH. vagina in what s called the transformation zone (McCance & Huether, 1998). The continuous replacement of columnar epithelial cells by squamous epithelial cells in this area makes these cells highly vulnerable to the uptake of foreign or abnormal genetic material. Research has demonstrated that HPV genetic material is present in more than 90 percent of premalignant and malignant squamous lesions of the uterine cervix (Stoler, 1996), particularly the presence of HPV messenger RNA and its protein expression. The viral proteins into which the mrna is translated release new virions from the cells for transmission and infection into other cells (McCance & Huether, 1998). Most commonly, malignancies in the transformation zone are squamous cell carcinomas (Lowdermilk, 2000). Papillomaviruses are known to produce primarily squamous epithelial growths in the genital tract. More than 80 types have been identified; HPV-16, 18, 31, and 45 are among those specifically described as cancer-associated (CancerNet, 1998) or high risk (Cancer Facts, 2001) by the National Cancer Institute. HPV types 16 and 18 have been classified as human carcinogens by the World Health Organization. Other HPV types (including 31, 33, 35, 45, 56 and 58) are also believed to be cancer causing (ACOG Annual Clinical Meeting, 2001). The highest risk types produce oncoproteins that bind normal tumor suppressor proteins and are capable of inducing cell growth and transformation (Kiviat, 1996; Stoler, 1996). The inactivation of tumor suppressor genes coupled with the activation of the cancer-promoting cellular oncogenes endemic to the human genome are involved in cancer development (McCance & Huether, 1998). HPV16 is considered most likely to infect the uterine cervix (Stoler, 1996). The varieties that are considered benign regarding carcinogenesis are HPV6 and HPV11. They produce visible lesions known as condyloma acuminatum or genital warts (CancerNet, 1998). Stoler notes that all HPV types must induce the pathological equivalent of a wart... because this is the disease that supports viral replication and virion production (1996, p. 1092). It can t be said, however, that HPV infection even with a cancer-associated type will lead to cancer (Higgins & Smith, 1997; Stoler, 1996). Like all cancers, cervical cancer is multi- 218 AWHONN Lifelines Volume 6 Issue 3

4 Box 1 continued. The National Cancer Institute s Bethesda System 2001 Terminology Speciman Type Indicate conventional smear (Pap smear) vs. liquid based vs. other Specimen Adequacy Satisfactory for evaluation (describe presence or absence of endocervical/transformation zone component and any other quality indicators, e.g., partially obscuring blood, inflammation, etc.) Unsatisfactory for evaluation... (specify reason) Specimen rejected/not processed (specify reason) Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify reason) General Categorization (optional) Negative for Intraepithelial Lesion or Malignancy Epithelial Cell Abnormality: See Interpretation/Result (specify squamous or glandular as appropriate) Other: See Interpretation/Result (e.g., endometrial cells in a woman 40 years of age) Automated Review If case examined by automated device, specify device and result. Ancillary Testing Provide a brief description of the test methods and report the result so that it is easily understood by the clinician. Interpretation/Result: Negative for Intraepithelial Lesion or Malignancy (when there is no cellular evidence of neoplasia, state this in the General Categorization above and/or in the Interpretation/Result section of the report, whether or not there are organisms or other nonneoplastic findings) Organisms: Trichomonas vaginalis Fungal organisms morphologically consistent with Candida spp Shift in flora suggestive of bacterial vaginosis Bacteria morphologically consistent with Actinomyces spp Cellular changes consistent with Herpes simplex virus Other Non-Neoplastic Findings (Optional to report; list not inclusive): Reactive cellular changes associated with inflammation (includes typical repair) radiation intrauterine contraceptive device (IUD) Glandular cells status posthysterectomy Atrophy Other Endometrial cells (in a woman 40 years of age) (Specify if negative for squamous intraepithelial lesion ) Epithelial Cell Abnormalities Squamous Cell Atypical squamous cells of undetermined significance (ASC-US) cannot exclude HSIL (ASC-H) Low-grade squamous intraepithelial lesion (LSIL) encompassing HPV/mild dysplasia/cin 1 High-grade squamous intraepithelial lesion (HSIL) encompassing moderate and severe dysplasia, CIS/CIN 2 and CIN 3 with features suspicious for invasion (if invasion is suspected) Squamous cell carcinoma Glandular Cell Atypical endocervical cells (NOS [not otherwise specified] or specify in comments) endometrial cells (NOS or specify in comments) glandular cells (NOS or specify in comments) Atypical endocervical cells, favor neoplastic glandular cells, favor neoplastic Endocervical adenocarcinoma in situ Adenocarcinoma endocervical endometrial extrauterine NOS Other Malignant Neoplasms: (specify) Educational Notes and Suggestions (optional) Suggestions should be concise and consistent with clinical follow-up guidelines published by professional organizations (references to relevant publications may be included). Source: Retrieved from June July 2002 AWHONN Lifelines 219

5 History & Presentation Box 2. National Consensus Guidelines Regarding Cervical Cancer Screening New guidelines regarding cervical cancer screening are now available for clinicians. These guidelines were developed by the American Society for Colposcopy and Cervical Pathology in conjunction with 29 other national organizations and federal agencies involved in women s health care and incorporate new technologies related to cervical cancer testing and diagnosing, and define for practicing clinicians both when and when not to use these new tools. In developing the guidelines, the consensus group evaluated the literature regarding cervical cancer of the last decade and used the results of the $25 million ALTS Trial of more than 5,000 women with abnormal Pap tests. Specifically, controversies have focused on the role of new technologies, including liquid-based cytology and DNA testing for human papillomavirus (HPV), a sexually transmitted virus that is the primary cause of cervical cancer. One of the important recommendations in the guidelines addresses women with the most common type of abnormal Pap test an inconclusive result referred to as ASC-US, or atypical squamous cells of undetermined significance. Before these guidelines, women with ASC-US would usually undergo several repeat Pap tests or undergo colposcopy. The new guidelines say the other approaches may still be used, but HPV testing is preferred whenever liquid-based Pap tests are used. If the liquid test is used, the laboratory can test the same sample used for the original Pap test for HPV, eliminating the need for a repeat provider visit. The test can quickly assure women who are HPV-negative that they are unlikely to have cervical cancer. Additionally, these women can then receive regular annual screening. Women who test positive for HPV need further evaluation. JAMA is making the guidelines available at no charge to clinicians and consumers at factorial. For example, coincident immunosuppression such as that produced by HIV infection or pregnancy or exposure to the chemical composition of cigarette smoke or other toxins, may enable HPV over time to produce cervical cancer (Lovejoy & Anastasi, 1994). Women diagnosed with cervical cancer may present with no symptoms. They may simply have decided that they postponed a necessary evil an annual gynecological exam and Pap test long enough. In fact, more than half of the women diagnosed with cervical cancer in the U.S. hadn t had an annual screen within the last three years despite many of these women having had contact with the health care system (Wright et al., 2000). These women are typically between 40 and 50 years of age at the time of diagnosis, though cervical changes may have been under way for a decade or more (Lowdermilk, 2000). Many women delay and/or are reluctant to have annual gynecological exams. Noller (1996) suggests that with greater choices today among contraceptive options, such as over-thecounter options, women don t have to see their health care provider for regular, annual exams in order to obtain contraception such as oral contraception a phenomenon that Noller suggests has distanced women from their health care providers. Nurses may note known risk factors when taking a woman s sexual history, including (CancerNet, 1998; Loudermilk, 2000; McCance & Huether, 1998), young age at time of sexual debut multiple sexual partners having one partner who has multiple other partners lower socioeconomic status African American or Hispanic American descent However, Noller (1996) concluded that race falls away as a risk factor when corrections are made for socioeconomic status. On the other hand, Noller found that the culpability of cigarette smoking found no such exoneration even after adjustments for sexual activity or human papillomavirus infection. An absolute risk factor for the development of invasive cancer of the cervix is a previous diagnosis of cervical intraepithelial neoplasia (CIN), or what s commonly known as cervical dysplasia (Kiviat, 1996; McCance & Huether, 1998). Women who have been diagnosed with CIN face five times the risk of developing invasive cervical cancer as compared to the general population, despite diligent long-term follow-up after treatment (Soutter et al., 1997). When abnormal epithelial growth penetrates the supportive basement membrane to which it s attached, and by which it s separated from underlying connective tissue, the diagnosis of invasive carcinoma is made (Lowdermilk, 2000; McCance & Huether, 1998). This may lead to manifestation of what s considered the classic symptom of invasive cancer: abnormal bleeding, especially postcoital bleeding (Lowdermilk, 2000). Squamous cell cancers, which represent 90 percent of cervical malignancies, can spread to the pelvic walls, bowels and bladder (Lowdermilk, 2000). Subsequently, rectal bleeding, hema- 220 AWHONN Lifelines Volume 6 Issue 3

6 turia and anemia may occur. Sufficiently large growths may result in pelvic or epigastric pain as well as leg or back pain. Structures close by, such as the ureters, the vagina and the lower uterine segment, are most often involved as the cancer spreads. When cervical cancer is invasive, symptoms are more apparent. For example, a woman may say she s experiencing abnormal bleeding, especially after intercourse, abnormal menses or postmenopausal bleeding. More subtle signs may include change in vaginal discharge accompanied by a different odor (McCance & Huether, 1998). As the cancer metastasizes, bloody urine or stool may develop and pelvic or epigastric pain may occur, especially if the lesion is large. Diagnostic Testing & Findings The Pap test has been widely credited for the early detection of cervical cancer. When identified, questionable lesions are removed, thus preventing further growth. Since the introduction of this test, some 50 years ago, there has been a 70 percent decline in cervical cancer deaths (McKillips, 1997; Thomas, 1997). It s claimed that the Pap test detects 90 percent of early cervical changes (Lowdermilk, 2000). During a cervical exam, a smear of cells that have been shed from the cervix and vagina is obtained using a small wooden spatula, cotton swab and a tiny brush. To obtain the most accurate cytologic exam, obtain the cervical cell specimens by swabbing the endocervix and scraping the exocervix (McCance & Huether, 1998). Because blood, mucus and inflammation can compromise the test, the ideal time for women to have the test is at two weeks after the end of menses. Women should be asked to abstain from intercourse for 48 hours prior to the test as semen can compromise the test as well. During pregnancy, there is an increased tendency of the cervix to bleed, increased congestion in the vaginal area and increased incidence of vaginal infections, all of which may create inflammatory changes. These can compromise the Pap test that is frequently done during the initial prenatal visit (Blackwell, Elam, & Blackwell, 2000). These confounding factors, plus the opportunity for error when collecting the sample, increase the need for this test to be performed on a regular basis, ideally annually in women with consistent normal results and more frequently in women who receive abnormal Pap results. Pap tests are designed to detect low-grade lesions, but if the test is performed incorrectly, lesions may be missed. If a Pap detects a lesion, it s then confirmed by colposcopically directed biopsy. The controversy surrounding the tests is in the management of low-grade lesions. As 70 to 80 percent of lesions spontaneously regress (The ALTS Group, 2000), controversy within practice exists as to whether to follow with repeated Pap smears or to treat by cryotherapy. Because the majority of low-grade lesions are a result of HPV, testing and typing HPV is being investigated. Expense in comparison to conventional Pap screening may become a limiting factor. The ThinPrep Pap Test has been introduced into practice as a replacement for conventional Pap testing. This test involves the transfer of cervical cells to a vial of preservative liquid rather than smearing the cells on a microscope slide (Austin & Ramzy, 1998; McKillips, 1997), thereby minimizing those things that might obscure the test, such as air-drying artifact (Paley, 2001). A very high percentage of women diagnosed with low-grade squamous intraepithelial lesions (SIL) (according to previous Bethesda guidelines) on the basis of a Pap smear test positively for HPV DNA (The ALTS Group, 2000, p. 397). New research toward the development of HPV vaccines is being conducted, and the use of HPV testing as a triage tool is being explored (Blumenthal, Ringers, McIntosh, & Gaffikin, 2001). New guidelines recently issued direct such follow-up and such testing when indicated (see Box 2). Of the approximately 50 to 60 million American women who receive an annual Pap test, approximately 1.7 percent of those women receive news of an abnormal result requiring additional follow-up including repeat Paps and testing with advanced technologies in some cases. Colposcopy enables clinicians to better visualize the cervix to identify areas to be biopsied (Lowdermilk, 2000). Specifically, a stereoscopic, binocular microscope is used after the application of either 3 or 5 percent acetic acid solution, which makes it easier to target the suspicious site (Lowdermilk, 2000). Biopsy of visualized lesions along with endocervical curettage (ECC) is very effective in diagnosing the extent of the abnormality. Endocervical curettage alone is not always diagnostic as lesions involving the transformation zone will be missed. Conversely, visualization of the ectocervix alone is not diagnostic and therefore ECC is an essential part of colposcopy and biopsy. June July 2002 AWHONN Lifelines 221

7 If the biopsy is positive, conization may be performed (Lowdermilk, 2000, p. 287). This involves the removal of a cone-shaped piece of tissue from the exocervix or endocervix under local anesthesia, if necessary, by any of several means and offers two benefits. It can establish the diagnosis, and, if the lesion is only microinvasive, it can simultaneously remove the cancer (Lowdermilk, 2000, p. 289). The diagnosis of invasive cancer warrants additional diagnostic testing to discern metastasis. Additional testing may include (Lowdermilk, 2000), liver and kidney function tests chest x-ray intravenous pyelogram barium enema computerized axial tomography bone scan additional biopsies Cervical cancer presents a challenge to health care practitioners from many aspects. Its pathophysiologic etiology is complex, its symptomatology is most often invisible, and its detection and treatment is costly (see Box 3 for additional information and resources). References ACOG Annual Clinical Meeting. (2001). Update in gynecology: Human papilloma viruses and cervical disease. Med-scape Women s Health [Online serial], 6(3). Retrieved from Austin, R. M., & Ramzy, I. (1998). Increased detection of epithelial cell abnormalities by liquid-based gynecologic cytology preparations: A review of accumulated data. Acta Cytologica, 42(1), Blackwell, D. A., Elam, S., & Blackwell, J. T. (2000). Cancer and pregnancy: A health care dilemma. Journal of Obstetric, Gynecologic, and Neonatal Nursing, 29(4), Blumenthal, P. D., Ringers, P., McIntosh, N., & Gaffikin, L. (2001). Editorial: Innovative approaches to cervical cancer prevention [Online]. Retrieved from Cancer Facts. (2001, January 8). Human papillomaviruses and cancer [Online]. Retrieved from fact/ 3_20.htm CancerNet. (1998, June 4). Human papillomaviruses and cancer: Cancer facts [Online]. Retrieved from nci.nih.gov Cuzick, J. (2000). Human papilloma testing for primary cervical cancer screening. Journal of the American Medical Association, 283(1), Follen, M., & Richards-Kortum, R. (2000). Emerging technologies and cervical cancer. Journal of the National Cancer Institute, 92(5), Geier, C. S., Wilson, M., & Creasman, W. (2001). Clinical evaluation of atypical glandular cells of undetermined significance. American Journal of Obstetrics and Gynecology, 184(2), Higgins, P. G., & Smith, P. E. (1997). Assessing cervical cancer risk. AWHONN Lifelines, 1(6), Kiviat, N. (1996). Natural history of cervical neoplasia: Overview and update. American Journal of Obstetrics and Gynecology, 175(4), Box 3. Getting All the Facts American Cancer Society: American Society for Colposcopy & Cervical Pathology: National Women s Health Information Center: Cancer Information Service, National Cancer Institute: Harvard Center for Cancer Prevention: Levie, M. D. (2001, November 12, 13). Management of atypical Pap smears. Management of AGUS Pap smears. In: Conference Report: Autumn in New York: Controversies in gynecology [Online]. Retrieved from Lovejoy, N. C., & Anastasi, J. K. (1994). Squamous cell cervical lesions in women with and without AIDS: Biochemical risk factors, prevention, and policy. Cancer Nursing, 17, Lowdermilk, D. L. (2000). Structural disorders and neoplasms of the reproductive system.in D.L.Lowdermilk,S.E.Perry,& I.M. Bobak (Eds.), Maternity and women s health care (pp ). St. Louis, MO: Mosby. McCance, K. L., & Huether, S. E. (Eds.). (1998). Pathophysiology: The biologic basis for disease in adults and children (3rd ed.). St. Louis, MO: Mosby-Year Book. McKillips, K. J. (1997). FDA approves more effective Pap test. AWHONN Lifelines, 1(5), Noller, K. (1996). Incident and demographic trends in cervical neoplasia. American Journal of Obstetrics and Gynecology, 175(4), Paley, P. J. (2001). Screening for the major malignancies affecting women: Current guidelines. American Journal of Obstetrics and Gynecology, 184(5), Soutter, W. P., de Barros Loppes, A., Fletcher, A., Monaghan, J. M., Duncan, I. D., Paraskevaidis, E., & Kitchener, H. C. (1997). Invasive cervical cancer after conservative therapy for cervical intraepithelial neoplasia. The Lancet, 349, Stoler, M. H. (1996). A brief synopsis of the role of the human papillomavirus in cervical carcinogenesis. American Journal of Obstetrics and Gynecology, 175(4), The Atypical Squamous Cells of Undetermined Significance/Low- Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. (2000). Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: Baseline data from a randomized trial. Journal of the National Cancer Institute, 92(5), Thomas, P. A. (1997). Postprocedural Pap smear: A leap of faith. Diagnostic Cytopathology, 17(6), Wright, T. C., Denny, L. D., Kuhn, D., Pollack, A., & Lorincz, A. (2000). HPV DNA testing of self-collected vaginal samples compared with cytologic screening to detect cervical cancer. Journal of the American Medical Association, 283(1), AWHONN Lifelines Volume 6 Issue 3