Cervical cancer is the sixth most common cancer to occur among American women, accounting for 6% of the cancers seen in women.  In many countries where Pap smears are not routinely performed, cervical cancer is the most common cause of cancer-related death among women.  Approximately 13,000 new cases of cervical cancer are diagnosed in the United States each year, while more than 50,000 new cases of precancerous changes in the cervix (called carcinoma in situ) will also be identified annually.  Currently, about 2% of all cancer deaths are due to cervical cancer in the United States.

In the past, I have reported on promising progress in the development of a vaccine against the strains of human papilloma virus (HPV) that are thought to cause more than 90% of cervical cancers.  As many as 70% of sexually active adults have been infected with at least one strain of HPV.  While not all HPV strains have been associated with an increase in the risk of cervical cancer, as many as 20% of adults are infected with the cancer-causing HPV type-16, which has been linked with cancers of the cervix and anus in as many as 1% of the infected population.  Thus, the development of an effective vaccine against HPV type-16 has been an area of intense research. 

In this week’s New England Journal of Medicine, Harvard Medical School scientists report on their initial evaluation of a new HPV type-16 vaccine.  Nearly 2,400 young women (ages 16 to 23) participated in the study.  Each volunteer was randomly assigned to receive a total of either three vaccine injections or three placebo (salt water) injections.  All study volunteers received frequent Pap smears for a median duration of about 18 months.  The HPV type-16 status of each woman before and after the injections was assessed using a test (RT-PCR) that detects and amplifies fragments of DNA from HPV type-16.  Among the volunteers who received the placebo injections, persistent HPV type-16 infection was detected in a significant number of the women.  Nine cases of precancerous cervical lesions were also identified among the women who received the placebo injections, and who were concomitantly diagnosed with HPV type 16 infections.  In contrast, none of women who received the vaccine went on to develop HPV type-16 infections, and none of the women in the vaccine group developed precancerous changes in the cervix, during the course of this study.

This study is a significant breakthrough in cancer prevention, and the potential impact of its findings will be of great importance in the United States.  In less developed countries, the potential public health impact will be even greater.  In developing countries where Pap smears are not routinely done, as many as 25% of all cancer deaths in women occur secondary to cervical cancer.  While the link between most other cancers and viral infection is not as strong as it is for cervical cancer, the development of an apparently effective vaccine against the oncogenic HSV type-16 will continue to fuel research and development of cancer prevention and treatment vaccines.  At my own parent institution, the John Wayne Cancer Institute, a vaccine against melanoma is undergoing international trials and has enrolled thousands of patients with melanoma.  The cancer immunologist’s dream of a safe, nontoxic and effective vaccine against all cancers is still many years away.  However, this report on the striking efficacy of a new anti-HPV type-16 vaccine is very good news, indeed, and offers hope and inspiration for further progress in this field.

Hormone Replacement Therapy:  More Bad News

Readers of this column are already well-informed about recent research that has deconstructed much of the decades-long mythology regarding postmenopausal hormone replacement therapy (HRT).  So, it should come as no surprise that another study has come along debunking previous claims for HRT’s manifold therapeutic benefits.  In this week’s Journal of the American Medical Association is a report on the impact of HRT and antioxidant vitamins on the progression of coronary artery disease in postmenopausal women.  The study evaluated 423 postmenopausal women with at least one narrowed coronary artery, and followed these volunteers for at least three years.  One group of women received supplemental estrogen (the women in this group who still had their uterus also received progesterone).  A second group received 400 IU of vitamin E and 500 mg of vitamin C twice daily.  The third and final group received placebo (sugar) pills.  The study volunteers were then followed by regular clinical exams during the study, and by a follow-up coronary angiogram at the end of the study.

The results of this study reinforce those of the pivotal Women’s Health Initiative Study findings that were published in July of this year: the women who were randomized to receive HRT in this new study not only failed to experience any coronary artery disease protection from their hormone supplements, but their coronary artery disease actually appeared to progress more rapidly, on the average, when compared to the women who received the placebo pills.  The women receiving antioxidant vitamins also appeared to experience an increase in the rate of coronary artery narrowing when compared to patients receiving only placebo pills.  While these differences failed to reach statistical significance in this relatively small study, its results are nonetheless quite intriguing.  What is especially compelling about this study is that the progression of coronary artery disease (CAD) in these patients with preexisting CAD was objectively measured using coronary angiograms.  When the researchers looked at the incidence of vascular disease complications among the study volunteers, they noted a statistically significant two-fold increase in the risk of heart attacks, strokes and death among the women receiving HRT.  The women receiving the antioxidant vitamins also tended to have a higher number of these serious events, although such findings were not statistically significant.

Although intriguing, this study involved women who had preexisting CAD, enrolled a relatively small number of volunteers, and evaluated them over a rather short duration.  This study should, therefore, be repeated, and should also include postmenopausal women without preexisting coronary artery disease, and should encompass larger numbers of volunteers, and a longer duration of follow-up. 

Alcohol, HRT & the Risk of Breast Cancer

Previous studies have shown a slight increase in the risk of developing breast cancer among women who consume more than two or three alcoholic drinks per day.  HRT has also been shown to significantly increase the risk of developing breast cancer with prolonged use.  In the current issue of the Annals of Internal Medicine, more than 44,000 women are being followed over an extended period of time to study the incidence of index diseases, including breast cancer.  The women participating in this study were followed between 1980 and 1994, and reported their use of HRT and their intake of alcohol on a regular basis.  During the study period, 1,722 of the women developed breast cancer.  When the researchers analyzed the impact of alcohol intake and HRT use, they found that the women who took HRT for five or more years and did not drink alcohol had a 32% increase in the risk of developing breast cancer when compared to the women who did not take HRT or alcohol.  Among the women who never used HRT but who consumed at least 1.5 to 2 alcoholic drinks per day, the risk of breast cancer was increased by 28% when compared to teetotalers who had never used HRT.  Women who used HRT for five or more years and consumed at least 1.5 to 2 alcoholic drinks per day experienced a 99% increase in the risk of developing breast cancer, or a nearly two-fold increase above the level experienced by women who did not drink alcohol and did not use HRT!  This study adds persuasive evidence to support previous findings of a link between breast cancer risk and HRT, and between increased alcohol consumption and the risk of breast cancer.  This study also suggests that the combination of HRT and two or more alcoholic drinks per day are additive in terms of their effects on breast cancer risk.

Briefly…

Annals of Internal Medicine: Many women are using non-prescription non-HRT herbal remedies to try and combat the side effects of menopause.  However, research into the efficacy and safety of these alternative treatments has been sporadic at best.  An extensive review of published research on this subject was undertaken in an effort to draw some meaningful conclusions.  Dong quai, evening primrose oil, Chinese herb mixtures, vitamin E and acupuncture did not appear to provide any objective improvement in hot flashes and other menopausal symptoms.  Soy appeared to be modestly effective, while isoflavone preparations did not appear to be as beneficial as soy.  Black cohosh appeared to offer substantial relief of hot flashes, but long-term safety information was lacking in previously published reports.  Both soy (and its derivative isoflavones) and black cohosh may exert their therapeutic effects by stimulating estrogen receptors in the breast and uterus, and the increased risk of developing cancer of these organs with chronic use of these supplements is unclear in studies published to date.  These concerns can only be answered through additional well-designed randomized research trials.