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ABSTRACT & COMMENTARY
Synopsis: The prognosis of cervical cancer in relation to human papillomavirus (HPV) type was evaluated in a population-based series of 399 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IV cervical cancer and with analyzable HPV data from tumor samples. The HPV nucleic acid detection was performed on DNA from paraffin-embedded specimens; overall survival, as well as cervical cancer-specific survival, was determined for each patient. The HPV 18-related cancers had a worse prognosis than the HPV 16-related cancers for patients with FIGO stage IB or II disease. Additional study to determine the mechanism for HPV 18-related cervical cancer may identify novel therapies for clinical testing.
Source: Schwartz S, et al. J Clin Oncol. 2001;19: 1906-1915.
Estimates from the american cancer society for US women are that 12,900 new cases and 4400 deaths will occur due to cervical cancer in the year 2001.1 These estimates reflect the continued dramatic decrease in cervical cancer incidence and death that has been achieved in US women, and this improvement has been made possible by routine use of the Papanicolaou (Pap) smear for early detection of preinvasive disease.2 Cervical cancer still remains a major cause of cancer-related mortality in women of reproductive age in many developing countries due to a lack of effective screening programs in these countries.2 Implementation of routine screening for these women would be anticipated to produce significant improvements in cervical cancer incidence and mortality. In addition, improvements are needed for all women with more advanced and invasive cervical cancers.
The role of infection with oncogenic types of HPV as an initiating event for cervical cancer has been well described.3 The oncogenic HPV 16 and HPV 18 viruses are found with the greatest frequency in invasive cervical cancer.4 An evaluation of prognosis associated with different HPV types could help elucidate the molecular basis of oncogenesis and potentially identify novel treatment strategies.5-7 The current study was performed to evaluate the association between HPV type and prognosis of patients with invasive cervical cancer.
This study by Schwartz and colleagues evaluated 399 women who had a diagnosis of FIGO stage IB to IV cervical cancer and also had analyzable HPV DNA in archival paraffin-embedded specimens. All of these patients were residents of 3 Washington state counties and had their diagnosis of cervical cancer made between 1986 and 1997. Median time for observation was 50.8 months, and total mortality (TM) and cervical cancer-specific mortality (CCSM) were determined. The cumulative TM of the 86 patients with HPV 18-related tumors was 33.7%, and the cumulative TM of the 210 patients with HPV 16-related tumors was 27.6%. The cumulative CCSM for patients with HPV 18-related tumors was 26.7%, and the cumulative CCSM for patients with HPV 16-related tumors was 18.1%. Hazard ratio (HR) adjusted for age, stage, and histologic type identified an increased risk for TM (HR, 2.2; 95% CI, 1.3-3.6) and CCSM (HR, 2.5; 95% CI, 1.4-4.4) for patients with HPV 18-related cancers compared to patients with HPV 16-related cancers. The strongest association was for patients with stage IB and IIA disease, with significant findings for HR both for TM (HR, 3.1; 95% CI, 2.3-4.2) and CCSM (HR, 5.8; 95% CI, 3.9-8.7). No association was seen for patients with stage IIB to IV disease. Schwartz et al concluded that HPV 18-related cervical cancers have a poor prognosis and speculate that understanding the basis for this poor prognosis may identify novel treatment approaches for these patients.
Comment by Mark R. Albertini, MD
The decline in cervical cancer incidence and mortality in US women represents the successful implementation of an effective screening modality (Pap smear) for a disease with a well-recognized preinvasive stage. Similar successful efforts are needed for women in developing countries, as substantial reductions in cervical cancer incidence and mortality could also be achieved for those women. The association of cervical cancer with HPV infection has allowed for study of the oncogenic process of this disease, and low-risk and high-risk types of HPV infection have been identified.2 The current study suggests differences in prognosis for cervical cancer depending on the type of high-risk HPV infection with which it is associated. The HPV 18-related cervical cancers are associated with a worse prognosis for patients with FIGO stage IB or IIA disease. It is not clear why the worse prognosis associated with HPV 18-related cancers compared with HPV 16-related cancers was only seen for FIGO stage IB and IIA disease, but not for stage IIB to IV disease. The HPV type may influence aspects of disease related to initial growth and spread of disease. Further study of the molecular pathogenesis of HPV 18 and HPV 16-related cervical cancer is needed and may identify novel strategies for treatment of this disease.
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2. Janicek MF, Averette HE. CA Cancer J Clin. 2001; 51:92-114.
3. Walboomers JM, et al. J Pathol. 1999;189:12-19.
4. Bosch FX, et al. J Natl Cancer Inst. 1995;87:796-802.
5. Villa LL, Schlegel R. Virology. 1991;181:374-377.
6. Burger RA, et al. J Natl Cancer Inst. 1996;88: 1361-1368.
7. Lombard I, et al. J Clin Oncol. 1998;16:2613-2619.