GYNECOLOGIC
ONCOLOGY
46,
4-5 (1992)
EDITORIAL Cervical Neoplasia in Elderly Women The authors of the report entitled “Is Human Papillomavirus Associated with Cervical Neoplasia in the Elderly?” are to be commended for conceiving a unique prevalence study designed to evaluate a subset of the population largely underserved in terms of basic medical care, especially in regard to preventive medicine. Since the initial publication of the Walton report, many have questioned the value of screening for cervical cancer in women over the age of 65. Eddy, in a cost analysis of cervical cancer screening, estimated that continued cervical cancer screening of patients over age 65 would identify few patients with invasive cancer and there would be insignificant prolongation of life among women screened [l]. While these calculations should be considered, many practicing clinicians recognize that these cost-analysis studies often suffer from simplification of presumptions. Recommendations that screening for cervical cancer can be stopped at age 65 assume adequate prior screening. Poor African-American urban women often fail to receive adequate screening, not only for cervical neoplasia, but also for breast cancer [2]. Data from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program have shown a remarkable decline in both the incidence of and the mortality due to cervical cancer with two exceptions, elderly women and black women. Approximately 20% of cervical cancer patients are elderly and these patients often are more likely to have advanced disease. This failure to improve the outcome among these two groups is not limited to cervical cancer but is true for almost all types of cancer. Only recently has this neglect of inclusion of women, elderly, and black patients been addressed in terms of designing clinical studies. The putative association of invasive cervical cancer and Human Papilloma Virus (HPV) may provide a measure of risk in otherwise asymptomatic patients. The authors described a prevalence of HPV infection in this elderly, black population of approximately 3.5%. This prevalence rate falls within the range of previous population studies which were conducted in younger women. In a recent
report from Germany, 4.1% (72/1737) of women over the age of 65 demonstrated the presence of HPV DNA in cervical smears. Patients with negative cervical cytology had a prevalence of HPV lower than that in those women with abnormal cervical cytology (3.0% versus 20.7%, respectively) [3]. Several specific criticisms of this report include the fact that although the patient population studied was allegedly presenting for a routine screening, 4 (1.5%) of the studied population of 263 patients had invasive cancer. This is an extremely high prevalence even given the background of this largely underserved population. This leads to the suspicion that rather than an asymptomatic population, some patients presented for screening due to symptoms of cervical carcinoma; if true, this would obviously increase both the rate of HPV positivity and the association of HPV and risk of cervical neoplasia. An additional criticism is that these patients were allegedly all screened and were noted to have a normal cervix. This must cast some doubt on the validity of the physical examination when no patient with an invasive lesion was suspected at the time of Pap test and HPV sampling despite the fact that two of the patients had advanced disease. If the authors’ intent was to truly establish prevalence, then elimination of patients who had previously undergone hysterectomy is likely to bias the study toward a lower prevalence rate; one would expect that some women would have undergone a hysterectomy related to cervical neoplasia. Since the authors have utilized vaginal lavage as a method for collecting the cells that are analyzed for HPV, this group of patients who lack a cervix would appear to be eligible. Inclusion of women found to have a cervix on examination only further invalidates this report for several reasons. First, women who underwent subtotal hysterectomy were most likely to be known to have no cervical dysplasia. Second, the accuracy of identifying a cervix in a postmenopausal woman with vaginal atrophy must be questioned. This determination is further cast in doubt if the same practitioners who missed 4
0090-8258/92 $4.00 Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.
EDITORIAL
the invasive cancers were those who identified the women with a cervix. The answer to the authors’ title/question is a definite “maybe.” The authors are correct in arguing for more studies and are careful to point out the limitations in this study. Other conclusions are less sound and appear to be drawn from manipulation of extremely small numbers of patients. As an example, the significant association between HPV and low-grade cervical neoplasia stretches the belief of a nonstatistician; one patient with CIN I positive for HPV would not appear to be a valid association. What this study does not support at this time is addition of HPV studies to routine clinical cervical cytology. Further studies will be important in defining if the presence of HPV or other high-risk factors may identify patients in this population who are at risk for developing cervical neoplasia and who would benefit from continued surveillance past the currently accepted endpoint of cervical cytology screening at age 65.
5
REFERENCES 1. Eddy, D. M. Screening for cervical cancer, Ann. Znt. Med. ll3,213226 (1990). 2. Whitman, S., Ansell, D., Lacey, L., Chen, E. H., Ebie, N., Dell, J., and Phillips, C. W. Patterns of breast and cervical cancer screening at three public health centers in an inner-city urban area, Am. J. Public Health 81, 1651-1653 (1991). 3. DeVilhers, E. M., Wagner, D., Schneider, A., Wesch, H., Munz, F., Miklaw, H., and zur Hausen, H. Human papillomavirus DNA in women without and with cytological abnormalities: Results of a 5-year follow-up study, Gynecol. Oncol. 44, 33-39 (1992).
John P. Curtin, M.D. Gynecology Service Department of Surgery Memorial Sloan-Kettering Cancer Center 1215 York Avenue New York, New York 10021
ONCOLOGY
46,
4-5 (1992)
EDITORIAL Cervical Neoplasia in Elderly Women The authors of the report entitled “Is Human Papillomavirus Associated with Cervical Neoplasia in the Elderly?” are to be commended for conceiving a unique prevalence study designed to evaluate a subset of the population largely underserved in terms of basic medical care, especially in regard to preventive medicine. Since the initial publication of the Walton report, many have questioned the value of screening for cervical cancer in women over the age of 65. Eddy, in a cost analysis of cervical cancer screening, estimated that continued cervical cancer screening of patients over age 65 would identify few patients with invasive cancer and there would be insignificant prolongation of life among women screened [l]. While these calculations should be considered, many practicing clinicians recognize that these cost-analysis studies often suffer from simplification of presumptions. Recommendations that screening for cervical cancer can be stopped at age 65 assume adequate prior screening. Poor African-American urban women often fail to receive adequate screening, not only for cervical neoplasia, but also for breast cancer [2]. Data from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program have shown a remarkable decline in both the incidence of and the mortality due to cervical cancer with two exceptions, elderly women and black women. Approximately 20% of cervical cancer patients are elderly and these patients often are more likely to have advanced disease. This failure to improve the outcome among these two groups is not limited to cervical cancer but is true for almost all types of cancer. Only recently has this neglect of inclusion of women, elderly, and black patients been addressed in terms of designing clinical studies. The putative association of invasive cervical cancer and Human Papilloma Virus (HPV) may provide a measure of risk in otherwise asymptomatic patients. The authors described a prevalence of HPV infection in this elderly, black population of approximately 3.5%. This prevalence rate falls within the range of previous population studies which were conducted in younger women. In a recent
report from Germany, 4.1% (72/1737) of women over the age of 65 demonstrated the presence of HPV DNA in cervical smears. Patients with negative cervical cytology had a prevalence of HPV lower than that in those women with abnormal cervical cytology (3.0% versus 20.7%, respectively) [3]. Several specific criticisms of this report include the fact that although the patient population studied was allegedly presenting for a routine screening, 4 (1.5%) of the studied population of 263 patients had invasive cancer. This is an extremely high prevalence even given the background of this largely underserved population. This leads to the suspicion that rather than an asymptomatic population, some patients presented for screening due to symptoms of cervical carcinoma; if true, this would obviously increase both the rate of HPV positivity and the association of HPV and risk of cervical neoplasia. An additional criticism is that these patients were allegedly all screened and were noted to have a normal cervix. This must cast some doubt on the validity of the physical examination when no patient with an invasive lesion was suspected at the time of Pap test and HPV sampling despite the fact that two of the patients had advanced disease. If the authors’ intent was to truly establish prevalence, then elimination of patients who had previously undergone hysterectomy is likely to bias the study toward a lower prevalence rate; one would expect that some women would have undergone a hysterectomy related to cervical neoplasia. Since the authors have utilized vaginal lavage as a method for collecting the cells that are analyzed for HPV, this group of patients who lack a cervix would appear to be eligible. Inclusion of women found to have a cervix on examination only further invalidates this report for several reasons. First, women who underwent subtotal hysterectomy were most likely to be known to have no cervical dysplasia. Second, the accuracy of identifying a cervix in a postmenopausal woman with vaginal atrophy must be questioned. This determination is further cast in doubt if the same practitioners who missed 4
0090-8258/92 $4.00 Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.
EDITORIAL
the invasive cancers were those who identified the women with a cervix. The answer to the authors’ title/question is a definite “maybe.” The authors are correct in arguing for more studies and are careful to point out the limitations in this study. Other conclusions are less sound and appear to be drawn from manipulation of extremely small numbers of patients. As an example, the significant association between HPV and low-grade cervical neoplasia stretches the belief of a nonstatistician; one patient with CIN I positive for HPV would not appear to be a valid association. What this study does not support at this time is addition of HPV studies to routine clinical cervical cytology. Further studies will be important in defining if the presence of HPV or other high-risk factors may identify patients in this population who are at risk for developing cervical neoplasia and who would benefit from continued surveillance past the currently accepted endpoint of cervical cytology screening at age 65.
5
REFERENCES 1. Eddy, D. M. Screening for cervical cancer, Ann. Znt. Med. ll3,213226 (1990). 2. Whitman, S., Ansell, D., Lacey, L., Chen, E. H., Ebie, N., Dell, J., and Phillips, C. W. Patterns of breast and cervical cancer screening at three public health centers in an inner-city urban area, Am. J. Public Health 81, 1651-1653 (1991). 3. DeVilhers, E. M., Wagner, D., Schneider, A., Wesch, H., Munz, F., Miklaw, H., and zur Hausen, H. Human papillomavirus DNA in women without and with cytological abnormalities: Results of a 5-year follow-up study, Gynecol. Oncol. 44, 33-39 (1992).
John P. Curtin, M.D. Gynecology Service Department of Surgery Memorial Sloan-Kettering Cancer Center 1215 York Avenue New York, New York 10021
