Abstract
A large, multicenter trial has demonstrated the efficacy of a human papillomavirus vaccine in preventing precancerous lesions in young women.
Merck and Co. Inc., recently announced the results of a large, Phase III clinical trial of Gardasil™, a vaccine against human papillomavirus (HPV). The vaccine protects against the two strains of HPV (16 and 18) that have been shown to be responsible for 70% of all cervical cancers.
“This is a tremendous breakthrough,” enthused David A Fishman of the New York University School of Medicine (NY, USA). “This is needed globally to reduce the high incidence of cervical cancer.”
The study, titled Future II, involved 12,167 women aged 16–26 years in 13 countries, none of whom had HPV at enrolment. Participants were randomized to receive a course of three injections of either the vaccine or placebo over a period of 6 months and were then followed for an average of 17 months.
In those women who remained free of HPV infection after the final dose, received all three doses and followed study protocol, no cases of HPV-16- or −18-related precancerous cervical lesions (precursors of cervical cancer) were identified compared with 23 cases in the placebo group, demonstrating 100% efficacy of the vaccine. In a broader group of women, including those who had missed doses or otherwise breached study protocol, the vaccine showed 97% efficacy.
Study author Kevin Ault is satisfied that this is still a very high efficacy in what “approaches real-world conditions.”
Principal investigator Professor Laura Koutsky, of the University of Washington (WA, USA), reported the results at the Infectious Diseases Society of America annual meeting. She commented that “this trial confirms that a vaccine can give young women a high level of protection from developing precancerous lesions and early cervical cancers” and added that she hoped in the future to see a vaccine giving protection against all HPV types with the potential to cause cervical cancer. “In that case, you could be blocking viruses that cause 87% of cervical cancer cases, instead of 70%.”
The vaccine also protects against the two strains of HPV(−6 and −11) responsible for 90% of all cases of genital warts. All four strains targeted by the vaccine can also cause benign changes in the cervix that may lead to abnormal Pap test results.
Merck and Co. Inc. plan to seek US Food and Drug Administration approval for Gardasil this year and aim to begin marketing in 2006. The vaccine is likely to be given to children aged 10–13 years, before they become sexually active. Boys are likely to be vaccinated along with girls, with the aim of preventing transmission. Some conservative groups have expressed concern that vaccinating children could encourage promiscuity in adolescents.
A rival vaccine, Cervarix™ by GlaxoSmithKline, which also targets HPV-16 and −18, is currently in clinical trials, with results expected next year.
Source: Merck Press Release.
Available online at: www.merck.com
Oral contraceptives give short-term protection against multiple sclerosis
Researchers from the Harvard School of Public Health (MA, USA) have found an association between the use of oral contraceptives and a short-term reduction in the risk of developing multiple sclerosis (MS). This supports earlier reports that estrogen delays the onset of MS-like disease in animal models. However, the effect of oral contraceptives appears to be short lived.
The study compared 106 women diagnosed with MS with 1001 matched controls. Women using oral contraceptives in the previous 3 years were 40% less likely to develop MS. Women were less likely to develop the first symptoms of MS during pregnancy but the postpartum period was associated with an increased likelihood of MS diagnosis.
Lead author Alvaro Alonso concluded that “Our findings suggest that high levels of exogenous [from outside the body] estrogens from OC use and of endogenous [from the body] estrogens during pregnancy may delay the first clinical attack of MS.”
Source: Alonso A, Jick SS, Olek MJ, Ascherio A, Jick H, Hernan MA: Recent use of oral contraceptives and the risk of multiple sclerosis. Arch. Neurol. 62(9),1362–1365 (2005).
in brief…
Demonstrates the efficacy of a new low-dose oral contraceptive for the treatment of premenstrual syndrome, including premenstrual dysphoric disorder. This randomized, placebo-controlled trial involved 450 women with symptoms of premenstrual dysphoric disorder who were randomized to active treatment or placebo. The active regimen was drospirenone 3 mg and ethinyl estradiol 20 μg for 24 days, followed by placebo for 4 days. A response, defined as a 50% or more drop in symptom severity, occurred in 48% of the active group compared with 36% in the placebo group.
Lee S, Kolonel L, Wilkens L, Wan P, Henderson B, Pike M: Int. J. Cancer (2005) [Epub ahead of print].
It has already been shown that hormone replacement therapy (HRT) is associated with an increased risk of breast cancer in Caucasian women. This study followed 55,371 women of African–American, Native Hawaiian, Japanese–American, Latina and Caucasian origin to determine whether this risk was present in all ethnic groups. The women, aged 45–75 years, were followed for an average of 7.3 years. Women who had received estrogen–progestin therapy for 5 years were found to have a 29% increased risk of developing breast cancer regardless of ethnicity, with a 10% increased risk associated with estrogen-only therapy in all except African–American women.
Kelly MG, O'Malley DM, Hui P et al.: Gynecol. Oncol. 98(3), 353–359 (2005).
Highlights the success of a new treatment program developed at the Yale School of Medicine (CT, USA) for an aggressive form of uterine cancer. After retrospectively reviewing 74 cases of stage I uterine papillary serous carcinoma, the investigators found that a combination of platinum-based chemotherapy and vaginal radiation was most effective in reducing recurrence of the disease.
Rates of episiotomy in childbirth too high
A group of Canadian researchers have exposed the lack of consistency between countries, regions and even individual healthcare providers, in what constitutes an acceptable rate of episiotomy – an incision to enlarge the vaginal opening during childbirth.
While episiotomy was once carried out routinely worldwide, since the 1980s, doctors in the USA and elsewhere have been issued guidelines recommending that the incision, which can take weeks to heal and lead to postpartum complications, should only be used when it is necessary to ensure a safe delivery.
However, investigators found that rates of episiotomy were still very high in some countries, for example Taiwan, where the procedure was carried out in all first-time vaginal births, and Spain, where the rate was 86%. The lowest rates were found in English-speaking and some Western European countries, notably Sweden.
Some of these differences are likely to be due to cultural views on pregnancy and childbirth, including the idea that this intervention may be seen as more progressive and modern among doctors in developing countries.
Lead author Ian Graham of the University of Ottowa (Canada) and his colleagues were particularly surprised to find that rates varied greatly within countries and sometimes even within institutions. He stated that this “does mean that the reasons for doing the episiotomies must be related to differences in the providers' attitudes and practices.”
Source: Graham ID, Carroli G, Davies C, Medves JM: Episiotomy rates around the world: an update. Birth 32(3), 219–223 (2005).
Complications in pregnancy lead to greater risk of stroke
Women who experience certain pregnancy complications may be at an increased risk of stroke, according to results reported recently at the American Neurological Association annual meeting. Investigators at the Duke University Medical Center (NC, USA) identified 164 women who suffered a stroke an average of 13.5 years after giving birth and compared them with 311 age- and delivery date-matched women who had not had a stroke.
Women who had experienced a stroke were 70% more likely to have suffered from complications during pregnancy, notably pre-eclampsia and gestational diabetes, which doubled the risk of later stroke.
Dr Monique Chireau, lead investigator of the study, emphasized that “what's especially important to note is that…these women [have] strokes at relatively young ages.” She went on to speculate that “lifestyle factors such as diet, family history of cardiovascular disease, genetic factors and possibly some underlying vascular abnormality may contribute to the increased risk of stroke for women with adverse pregnancy outcomes.”
The researchers concluded that long-term preventive treatment with low-dose aspirin might be justified in those women at particular risk of stroke.
Source: Chireau MV, Bushnell CD, Brown H, Goldstein LB, Bastian LA: Pregnancy complications are associated with stroke risk later in life. American Neurological Association Annual Meeting. Chicago, IL, USA (2005) (Abstract 222).
Digital mammography may be more effective in certain patients
Digital mammography may detect up to 28% more cancers than film mammography in women aged 50 years and under, pre- or perimenopausal women and those with dense breast tissue, according to a study published online in the New England Journal of Medicine.
“The data show that digital mammography is, on average, as good at detecting breast cancer as film mammography – and in some important subgroups of women, digital performs even better” stated lead researcher Constantine Gatsonis.
The size and rigor of this trial make it a landmark study in the diagnostic accuracy of mammograms. A total of 49,528 women with no symptoms of breast cancer were enrolled at 33 centers across the USA and given both digital and film mammograms. Mammograms were evaluated by two separate radiologists and breast cancer status confirmed by biopsy or follow-up mammogram.
Computer technology is increasing the efficacy of breast cancer screening, according to two recent studies of digital and computer-aided mammography.
Gatsonis sees the results of this study as a baseline for further research to improve breast cancer screening: “Neither film nor digital mammography is able to catch every cancer, so this study data can be used to develop and improve mammography in the coming years. And that is good news for women's health.”
Another large study has recently revealed that a computer-aided mammography detection (CAD) system significantly improves detection rates of small (under 1 cm) invasive cancers, particularly in women with dense breast tissue.
The study examined 27,274 mammograms, 19,402 of which used the CAD system. Each mammogram was first reviewed by radiologists, before the CAD system was used to identify and mark any areas for concern. The mammograms were then rereviewed by the radiologists.
“Overall, we saw a 16% increase in the cancer detection rate,” stated lead author Dr Thomas Cupples but, he added, “the more important question is do we find more cancers earlier, when they are smaller and most curable?” CAD dramatically increased the detection rate of small, invasive cancers by 164%. Source: Pisano ED, Gatsonis C, Hendrick E et al.: Diagnostic performance of digital versus film mammography for breast-cancer screening. N. Engl. J. Med. (2005) [Epub ahead of print]. Cupples TE, Cunningham JE, Reynolds JC: Impact of computer-aided detection in a regional screening mammography program. AJR Am. J. Roentgenol. 185(4), 944–950 (2005).
Women with uterine cancer face increased risk of ovarian cancer
New research suggests that up to a quarter of younger women with uterine cancer suffer from concurrent ovarian cancer.
In a sample of 102 women under the age of 46 years undergoing hysterectomy for uterine cancer, 26 were found to have ovarian cancer, of which 23 were new cancers.
Young women with uterine cancer may be offered ovary-sparing treatment but the authors suggest that this might not be advisable. “Based on our data, we would recommend a cautious approach to (ovary-sparing treatment) in young patients with uterine cancer,” they conclude “the high incidence of coexisting [cancer] in the ovaries and the young age of diagnosis suggest an increased susceptibility of the reproductive organs.”
Source: Walsh C, Holschneider C, Hoang Y, Tieu K, Karlan B, Cass I: Coexisting ovarian malignancy in young women with endometrial cancer. Obstet. Gynecol. 106(4), 693–699 (2005).
Novel risk factors for breast cancer
Results of a study published in a recent issue of the British Medical Journal suggest that left-handed women are more than twice as likely to develop premenopausal breast cancer.
Researchers examined the medical records of over 12,000 healthy middle-aged Dutch women. Even after adjustment for breast cancer risk factors such as socioeconomic status, tobacco use and family history, the association with left handedness remained strong.
The authors speculate that “the origin of the association may lie in intrauterine exposure to steroid hormones,” noting that women exposed in the womb to certain hormonal drugs were more likely to be left-handed. In utero exposure to sex hormones could also induce changes in breast tissue.
“Although the underlying mechanisms remain elusive, our results support the hypothesis that left handedness is related to increased risk of breast cancer” they conclude.
A separate study on breast cancer risk, also published recently in the British Medical Journal, has suggested that high levels of daily stress might lower women's risk of developing breast cancer. In a study following 6500 Danish women for 18 years, women who rated their stress levels as high were 40% less likely to develop breast cancer than those who felt they experienced low stress at the start of the study.
The authors suggest that these findings might relate to changes in sex hormone levels with chronic stress. However, these changes are not considered healthy and may contribute to other leading causes of death in women, particularly cardiovascular disease.
Source: Ramadhani MK, Elias SG, van Noord PA, Grobbee DE, Peeters PH, Uiterwaal CS: Innate left handedness and risk of breast cancer: case-cohort study. Br. Med. J. (2005) [Epub ahead of print].
Nielsen NR, Zhang ZF, Kristensen TS, Netterstrom B, Schnohr P, Gronbaek M: Self reported stress and risk of breast cancer: prospective cohort study. Br. Med. J. 331(7516), 548 (2005).