The most cost-effective screening strategy was vaccination at age 12 and cytologic screening every 3 years beginning at age 25. Using this approach, the lifetime risk of cervical cancer would be reduced by 94% compared with no screening—a spectacular improvement.
HPV vaccines will become available in the next several years, at which time we will need to determine their appropriate use in industrialized nations, such as the United States, where about 3,900 cervical cancer deaths will occur this year, as well as in developing countries. Worldwide, roughly 500,000 women die of the disease each year. In developing countries, the vaccine would decrease the incidence of dysplasia by more than 50%, even if used as a single modality.
Clinical implications. Although most dysplasias and carcinomas are related to HPV 16/18, it is imperative that we continue to screen to rule out infection with other high-risk subtypes. Eventually, a polyvalent vaccine may enable us to vaccinate for all known high-risk subtypes.
REFERENCE
1. Koutsky LA, Ault KA, Wheeler CM, et al. for the Proof of Principle Study Investigators. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med. 2002;347:1645-1651.
HRT increases risk of ovarian cancer
Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women’s Health Initiative randomized trial. JAMA. 2003;290:1739–1748.
The Women’s Health Initiative has produced the single largest randomized, prospective trial comparing estrogen, continuous estrogen-progesterone, and placebo. Recent findings from this population include an increased risk of breast cancer, heart disease, dementia, and vascular thrombosis with HRT use.
Now Anderson and colleagues have reported on the association between gynecologic cancers and HRT—specifically, the estrogen-progestin combination. In the randomized, double-blind study involving 16,608 postmenopausal women, participants were given 0.625 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and the main outcome measure was invasive cancer of the ovary or endometrium. After an average follow-up of 5.6 years, Anderson et al found 32 cases of invasive ovarian cancer, 58 cases of endometrial cancer, 1 case of non-endometrial uterine cancer, 13 cases of cervical cancer, and 7 cases of other gynecologic cancers.
Compared with controls, women taking HRT experienced a significantly increased incidence of ovarian cancer, with a hazard ratio of 1.58 (95% CI, 0.77–3.24). For endometrial cancer, the hazard ratio was 0.81 (95% CI, 0.48–1.36). The groups did not differ significantly in regard to the other cancers.
More endometrial biopsies. Another important finding from this study is the greater need for endometrial biopsies among women taking HRT (33% versus 6%; P<.001>
Other trials also have reported an increased risk of ovarian cancer with HRT use, as well as the decreased risk of endometrial cancer.
Because of the greater risk associated with HRT, indications for it have changed. Now most HRT users are young and take the therapy to relieve vasomotor symptoms. These women should be counseled about the risks outlined in the Women’s Health Initiative, as well as the importance of endometrial biopsies to evaluate any abnormal bleeding.
Clinical implications. In the next 5 years, alternative therapies such as selective estrogen receptor modulators are likely to replace HRT. Until then, I will continue to prescribe HRT, but only in symptomatic women for a period of less than 5 years.
Related Reading
- Hempling RE, Wong C, Piver MS, et al. Hormone replacement therapy as a risk factor for epithelial ovarian cancer: results of a case-control study. Obstet Gynecol. 1997;89:1012–1016.
- Kaufman DW, Kelly JP, Welch WR, et al. Noncontraceptive estrogen use and epithelial ovarian cancer. Am J Epidemiol. 1989;130:1142–1151.
- Purdie DM, Bain CJ, Siskind V, et al. Hormone replacement therapy and risk of epithelial ovarian cancer. Br J Cancer. 1999;81:559–563.
- Risch HA. Estrogen replacement therapy and risk of epithelial ovarian cancer. Gynecol Oncol. 1996;63:254–257.
- Rodriguez C, Calle EE, Coates RJ, et al. Estrogen replacement therapy and fatal ovarian cancer. Am J Epidemiol. 1995;141:828–835.
- Rodriguez C, Patel AV, Calle EE, et al. Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA. 2001;285:1460–1465.
Consolidation therapy extends disease-free interval
Markman M, Liu PY, Wilczynski S, et al. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy. Southwest Oncology Group and Gynecologic Oncology Group Trial. J Clin Oncol. 2003;21:2460–2465.
Standard therapy for ovarian cancer consists of 6 courses of a platinum (cisplatin or carboplatin) and taxane (paclitaxel or docitaxel) regimen. Following such therapy, second-look laparotomy or laparoscopy once was widely performed. However, that strategy has not been shown to increase survival: 50% of second looks for suspected ovarian cancer are pathologically positive, while an additional 25% are pathologically positive within 3 years.