New Pap Smear Test Makes it Easier to Identify Earliest Cervical Cancer Cells

GENESEE COUNTY
THE FLINT JOURNAL FIRST EDITION

A better Pap test
In the past 50 years, Pap tests have reduced the deaths of women from cervical cancer by 70 percent, and new imaging systems are helping experts catch tiny cancer cells earlier.

A new imaging system in use at McLaren Regional Medical Center is adding extra precision to catching cervical cancer early.

It means that after years of normal Pap tests, women can be assured that tiny cancer cells aren't missed and left to one day develop into invasive cervical cancer.

"This is like a set of tireless eyes looking at each patient's test along with the cytotechnologist and pathologist," said Greg Huffman, a McLaren cytotechnologist.

Largely behind-the-scenes advances are making the Pap test more precise than ever, yet the uncomfortable exam remains the same.

But most women have no idea who's reading their Pap tests after their annual visit to the gynecologist.

"My goal really is to educate people about what's happening with their lab tests," said Huffman, who estimates McLaren processes 13,000 Pap tests a year.

During a Pap test, a physician collects a specimen by scraping cells from the cervix that are later examined under a microscope.

McLaren's new FocalPoint, Huffman said, is an automated microscope that alerts cytotechnologists to suspicious slides likely holding problem cells.

The imaging system's greatest advantage is in pinpointing high-grade lesions - pre-cancerous cells that are smaller than normal cells but will one day could cause cervical cancer.

In the cytotechnology industry, they're nicknamed "litigation cells" because after years of normal Pap tests, a woman may have advanced cancer that should have been caught by routine Pap tests.

Not only is the evaluation of Pap tests getting better, but also the slides themselves are easier to read.

Flint-area hospitals and Owosso Memorial Healthcare also are now using liquid-based cervical screening, which is commonly called by the trade name Thin Prep.

The liquid-based method reduces excessive blood, bacteria or other debris that can make a specimen unsatisfactory. What's left for cytotechnologists to review is a thin layer of cells in which it's easier to identify abnormal cells.

Liquid-based screening is used in a majority of the 1,300 to 1,500 Pap tests performed at Hurley Medical Center each month, said Hurley cytotechnologist Sheila Moore.

Genesys reviews 12,000 tests a year and is considering taking the next step to use an imaging system similar to McLaren's.

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Cervical Cancer Vaccine Touches Hot-Button Issues

Cervical Cancer Vaccine Proposals Stall:
1 of 23 state bills to require the shots for young girls has passed

For a time, Georgia was poised to become the latest state to require preteen girls to be vaccinated against a virus that causes cervical cancer.

A powerful state Republican lawmaker proposed making the vaccine mandatory for girls entering sixth grade, and the governor included $4.3 million in his budget to make it available to some 13,000 girls whose family's insurance policies wouldn't cover it.

But state lawmakers nixed the plans after aggressive lobbying by religious conservatives, who argued that vaccinating young girls could promote promiscuity. The human papillomavirus that causes cervical cancer is transmitted through sexual contact.

Similar proposals were introduced in 23 other states and the District of Columbia, but only Virginia has signed such a mandate into law.

Proposals in many states died or were watered down to only provide parents with educational materials instead of requiring the vaccine. In Texas, Gov. Rick Perry signed an executive order requiring vaccinations for sixth-grade girls, but the Legislature then passed a bill blocking the order.

Over the past several months, a vaccine that once was hailed as a breakthrough to prevent cancer deaths has become embroiled in some of the nation's most politically charged issues: teen sex, parental control, state mandates, a backlash against vaccines and a suspicion of drug companies.

"It encapsulates so many issues that are at the core of politics and health policy right now," said Alina Salganicoff, director of women's health policy at the Kaiser Family Foundation.

The vaccine Gardasil was approved by the Food and Drug Administration in June 2006. The federal Advisory Committee on Immunization Practices followed with a recommendation that all girls be vaccinated at age 11 or 12. The three-dose treatment costs $360.

Cervical cancer kills 10 women a day in the U.S. and one in four U.S. women ages 14 to 59 is infected with HPV, according to a recent report from the federal Centers for Disease Control and Prevention. While Gardasil is not a magic bullet, it protects against the strains of HPV that cause 70 percent of cervical cancer cases.

With the vaccine potentially saving many lives, cervical cancer survivor Lori Grice said, she was "completely dumbfounded" that it had become fodder for the culture wars.

"If this were a vaccine for prostate cancer they would have to call in the National Guard to keep the men from storming the place," said Grice, of Statesboro, Ga.

Grice said she plans to have her 6-year-old daughter vaccinated when she's old enough. She said her daughter can "make every right choice," avoiding IV drug use and premarital sex, "but she can marry someone who's a carrier of HPV, develop cervical cancer and die."

Some parents insist that they should decide when their preteen daughter should be offered a vaccine that involved a discussion about sex.

Moira Gaul, director of women's and reproductive health at the conservative Family Research Council, said her group doesn't oppose the vaccine, but doesn't want it required.

"We think parents ought to be given a choice about what is best for their children," she said.

Others were turned off by what they saw as heavy-handed lobbying by the drug's maker, Merck and Co. Critics saw a drug company trying to get rich.

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HPV Vaccine Stops Cervical Cancer

HPV Vaccine Stops Cervical Cancer
Ivanhoe Newswire
By Vivian Richardson, Ivanhoe Health Correspondent

ORLANDO, Fla. (Ivanhoe Newswire) -- Almost zero. That's how low the chances of developing cervical cancer caused by two types of the human papillomavirus is for women who get vaccinated against the virus.

A new study reveals women vaccinated with a vaccine for HPV types 16 and 18, which are responsible for nearly 70 percent of all cases of cervical cancer, have close to no chance of developing cervical cancer.

"We were able to show a very high degree of efficacy of this vaccine," study author Kevin Ault, M.D., told Ivanhoe. The researcher from Emory University School of Medicine in Atlanta said this study shows the vaccine to be around 98-percent effective and safe.

Researchers studied more than 12,000 women between ages 15 and 26. Half the women were given the true vaccine, while the other half were given a placebo. The researchers report in women who had not been exposed to either HPV 16 or HPV 18, the vaccine was 98-percent effective at preventing the early stages of cervical cancer. When women who tested positive for one of the two strains of HPV were included in the data, the vaccine was only 44-percent effective.

"What this study showed is that it's very, very important to get women before they are exposed to the viruses, and therefore you have to expose them very young to the vaccine," William Schaffner, M.D., told Ivanhoe. Dr. Schaffner was not part of this study, but as professor and chair of the department of preventive medicine at Vanderbilt University in Nashville, Tenn., he said this study reaffirms the need to vaccinate young women.

"The concept that we now have a vaccine that that will be effective at preventing up to 70 percent of cervical cancers is very, very exciting, and it's a great milestone in women's health," Dr. Schaffner said. Though Pap smears can catch cervical cancer early enough to effectively cure it, not every woman is getting the screening on a regular basis.

"There are many women who don't adhere to the screening program. If we could but immunize them early on, we would benefit even those women who don't get regular attention when they get older," Dr. Schaffner said.

A recent study from researchers at Brown University in Providence, R.I., suggested genital skin cancer is three-times more likely to kill women than men. Doctors believe at least some cases of this rare cancer is caused by the human papillomavirus (HPV). The virus can hide out in the skin cells of unsuspecting men and women, waiting for decades before causing cancer. Elderly women, unfortunately, are more likely to die because skin cancers in the genital area often go undetected until it's too late.

Dr. Ault said it is still too early to say the HPV vaccine will wipe out cervical cancer. "There are about a dozen different types of HPV that cause cervical cancer, and we have the two worst ones in this vaccine, but there are still others," he said.

The vaccine is recommended for women ages 9 to 26. Three injections are given over six months.

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Human Papillomavirus Vaccine — Opportunity and Challenge, New England Journal of Medicine, 5/10/07

Editorial
New England Journal of Medicine
Volume 356:1990-1991 May 10, 2007 Number 19

Human Papillomavirus Vaccine — Opportunity and Challenge

Lindsey R. Baden, M.D., Gregory D. Curfman, M.D., Stephen Morrissey, Ph.D., and Jeffrey M. Drazen, M.D.

In this issue of the Journal, we publish three Original Articles,^1,2,3 two Perspective articles,^4,5 two editorials,^6,7 a letter to the editor,⁸ and an audio interview⁹ on the subject of human papillomavirus (HPV). We bring together this unique body of information in response to the enormity of the health problems that stem from HPV and the broad interest that has been kindled by the possibility of preventing HPV-related cervical cancer and other anogenital conditions through vaccination.

The HPV vaccine is the first vaccine explicitly designed to prevent cancer induced by a virus. (The hepatitis B vaccine was not primarily designed to prevent cancer.) As noted in the Perspective article by Agosti and Goldie,⁵ the consequences of HPV infection are a global health concern that disproportionately affects those in developing countries. The potential ability to reduce the burden of HPV-related disease by vaccination against certain disease-inducing strains of the virus has created a volatile intersection between the community's interest in limiting the transmission of infectious diseases and promoting health on the one hand and social mores on the other, as discussed by Charo in her Perspective article⁴ and related audio interview (podcast available at www.nejm.org).⁹ However, this volatility should not keep us from recognizing the enormous potential for medical progress and from addressing the numerous unanswered questions that remain.

The finding that infection with HPV is a critical factor in the majority of cases of cervical cancer allowed the development of strategies to prevent this form of oncogenesis. It is important to note that several other cancers are also associated with HPV infection, including head and neck cancers, as demonstrated by D'Souza and colleagues.³ Although there are many HPV serotypes, two of them — 16 and 18 — account for the lion's share of the oncogenesis. The data that are presented in reports on the vaccine efficacy trials in this issue of the Journal^1,2 confirm the success in reducing the incidence of precancerous cervical lesions with vaccine directed against the HPV-16 and HPV-18 serotypes.

Although this is a remarkable achievement, the efficacy of the vaccine is limited by at least these two factors. First, not all cervical cancer is caused by HPV-16 or HPV-18, and second, it appears necessary to vaccinate young women before they are infected with these two serotypes. Also, whether this approach will extend the paradigm of vaccination to the prevention of death and disability from cervical cancer is an unanswered question.

It is difficult to show that an intervention prevents cancer, given the relatively long induction phase between exposure to an inducing agent and development of disease. Thus, key surrogate markers, in this case cervical intraepithelial neoplasia grades 2 and 3, were used so that data could be gathered in a timely fashion. However, correlation with the ultimate outcome — cancer prevention — will require the long-term observation of a large number of treated women. We must also carefully monitor for unintended adverse consequences of vaccination. For example, when selective immunologic pressure is applied with vaccination, the potential exists for nonvaccine-related strains to emerge as important oncogenic serotypes. These critical points are clarified in the editorial by Sawaya and Smith-McCune.⁶

Many other questions are raised by these remarkable data. Should young men be vaccinated? What is the durability of immune protection? Could fewer than three vaccinations provide adequate protection? Will future HPV vaccines extend protection to cover additional pathogenic serotypes? Will the economics allow this therapy to reach all who may benefit, such as those in the developing world? Might HPV vaccination be beneficial in preventing other, noncervical HPV-induced cancers (such as HPV-related oropharyngeal cancer³)?

There is no doubt that the findings reported in this issue of the Journal open a new field at the interface of basic science, clinical medicine, public health, and public policy. It is important to keep in mind that these new treatments raise many scientific, medical, economic, and sociological questions. We have begun an exciting journey; we need to continue in the right direction.

References

1. The FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007;356:1915-1927. [Free Full Text]
2. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against the human papillovmavirus to prevent anogenital diseases. N Engl J Med 2007;356:1928-1943. [Free Full Text]
3. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 2007;356:1944-1956. [Free Full Text]
4. Charo RA. Politics, parents, and prophylaxis -- mandating HPV vaccination in the United States. N Engl J Med 2007;356:1905-1908. [Free Full Text]
5. Agosti JM, Goldie SJ. Introducing HPV vaccine in developing countries -- key challenges and issues. N Engl J Med 2007;356:1908-1910. [Free Full Text]
6. Sawaya GF, Smith-McCune K. HPV vaccination -- more answers, more questions. N Engl J Med 2007;356:1991-1993. [Free Full Text]
7. Syrjanen S. Human papillovmaviruses in head and neck carcinomas. N Engl J Med 2007;356:1993-1995. [Free Full Text]
8. Stewart S. Mandating HPV vaccination -- private rights, public good. N Engl J Med 2007;356:1998-1999. [Free Full Text]
9. Interview with R. Alta Charo. (Available at http://content.nejm.org/cgi/content/full/356/19/1905/DC1.)

Related Letters:

Mandating HPV Vaccination — Private Rights, Public Good
Stewart A. M.
Extract | Full Text | PDF
N Engl J Med 2007; 356:1998-1999, May 10, 2007. Correspondence

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Politics, Parents, and Prophylaxis — Mandating HPV Vaccination in the United States, New England Journal of Medicine, 5/10/07

Editorial
New England Journal of Medicine
Volume 356:1991-1993 May 10, 2007 Number 19

Politics, Parents, and Prophylaxis — Mandating HPV Vaccination in the United States

R. Alta Charo, J.D.

Cancer prevention has fallen victim to the culture wars. Throughout the United States, state legislatures are scrambling to respond to the availability of Merck's human papillomavirus (HPV) vaccine, Gardasil, and to the likely introduction of GlaxoSmithKline's not-yet-approved HPV vaccine, Cervarix, which have been shown to be effective in preventing infection with HPV strains that cause about 70% of cases of cervical cancer. At the Centers for Disease Control and Prevention (CDC), the Advisory Committee on Immunization Practices (ACIP) has voted unanimously to recommend that girls 11 and 12 years of age receive the vaccine, and the CDC has added Gardasil to its Vaccines for Children Program, which provides free immunizations to impoverished or underserved children.

Yet despite this federal imprimatur, access to these vaccines has already become more a political than a public health question. Though the more important focus might be on the high cost of the vaccines — a cost that poses a genuine obstacle to patients, physicians, and insurers — concern has focused instead on a purported interference in family life and sexual mores. This concern has resulted in a variety of political efforts to forestall the creation of a mandated vaccination program. In Florida and Georgia, for example, efforts to increase adoption of the vaccine have been stalled by legislative maneuvering. The Democratic governor of New Mexico has announced that he will veto a bill that mandates vaccinations. And the Republican governor of Texas came under fire (and under legal attack from his own attorney general) when he issued an executive order to the same effect, mandating that all girls entering the sixth grade receive the vaccine; the policy was attacked as an intrusion on parental discretion and an invitation to teenage promiscuity. But all these measures included a parental right to opt out, whether on religious or secular grounds. The opposition seemed more about acknowledging the realities of teenage sexuality than about the privacy and autonomy of the nuclear family.

For more than a century, it has been settled law that states may require people to be vaccinated, and both federal and state court decisions have consistently upheld vaccination mandates for children, even to the extent of denying unvaccinated children access to the public schools. State requirements vary as to the range of communicable diseases but are often based on ACIP recommendations. School-based immunization requirements represent a key impetus for widespread vaccination of children and adolescents¹ and are enforceable even when they allegedly conflict with personal or religious beliefs.² In practice, however, these requirements usually feature exceptions that include individual medical, religious, and philosophical objections.

View larger version (30K): [in this window] [in a new window] State Laws and Proposed Legislation Mandating HPV Vaccination. All legislation mandating HPV vaccination includes some form of parental opt-out. The Texas mandate is the result of an executive order from the governor, and its legality is being challenged by the attorney general of Texas. There is also legislation under consideration in Texas that would prohibit a mandate. If passed, it would override the executive order. The Virginia law was passed by the legislature and signed by the governor. The New Mexico legislation was passed by the House and Senate and was then vetoed by the governor. Bills in California and Maryland have been withdrawn for consideration, and the bill in South Carolina has been tabled. Neither Alaska nor Hawaii has considered a mandate. Legislation that makes provisions for funding is under consideration in many states but is not shown here. The various bills would require insurance companies to cover vaccination, allocate state funds, direct agencies to apply for federal funds, or some combination. Information is from the National Conference of State Legislatures and is accurate as of April 27, 2007.

HPV-vaccination mandates, which are aimed more at protecting the vaccinee than at achieving herd immunity, have been attacked as an unwarranted intrusion on individual and parental rights. The constitutionality of vaccination mandates is premised on the reasonableness of the risk–benefit balance, the degree of intrusion on personal autonomy, and, most crucial, the presence of a public health necessity. On the one hand, to the extent that required HPV vaccination is an example of state paternalism rather than community protection, mandatory programs lose some of their justification. On the other hand, the parental option to refuse vaccination without interfering in the child's right to attend school alters this balance. Here the mandates act less as state imperatives and more as subtle tools to encourage vaccination. Whereas an opt-in program requires an affirmative effort by a parent, and thus misses many children whose parents forget to opt in, an opt-out approach increases vaccination rates among children whose parents have no real objection to the program while perfectly preserving parental autonomy.

Opposition to HPV vaccination represents another chapter in the history of resistance to vaccination and, on some levels, reflects a growing trend toward parental refusal of a variety of vaccines based on the (erroneous) perception that many vaccines are more risky than the diseases they prevent. In most cases, pediatricians have largely restricted themselves to educating and counseling objecting families, since it is rare that the risks posed by going unvaccinated are so substantial that refusal is tantamount to medical neglect. In the case of HPV vaccine, parents' beliefs that their children will remain abstinent (and therefore uninfected) until marriage render it even more difficult to make the case for mandating a medical form of prevention. Even with an opt-out program, critics may argue that the availability of a simple and safe alternative — that is, abstinence — undermines the argument for a state initiative that encourages vaccination through mandates coupled with an option for parental refusal.

But experience shows that abstinence-only approaches to sex education do not delay the age of sexual initiation, nor do they decrease the number of sexual encounters.³ According to the CDC, though only 13% of American girls are sexually experienced by 15 years of age, by 17 the proportion grows to 43%, and by 19 to 70%.⁴ School-based programs are crucial for reaching those at highest risk of contracting sexually transmitted diseases, and despite the relatively low rate of sexual activity before age 15, the programs need to begin with children as young as 12 years: the rates at which adolescents drop out of school begin to increase at 13 years of age,¹ and younger dropouts have been shown to be especially likely to engage in earlier or riskier sexual activity.

Another fear among those who oppose mandatory HPV vaccination is that it will have a disinhibiting effect and thus encourage sexual activity among teens who might otherwise have remained abstinent. This outcome, however, seems quite unlikely. The threat of pregnancy or even AIDS is far more immediate than the threat of cancer, but sex education and distribution of condoms have not been shown to increase sexual activity. Indeed, according to a study conducted by researchers at the University of Pennsylvania, it is the comprehensive sex-education approaches that include contraceptive training that "delay initiation of sexual intercourse, reduce frequency of sex, reduce frequency of unprotected sex, and reduce the number of sexual partners."⁵ Opposition to the HPV-vaccination mandates, then, would seem to be based more on an inchoate concern: that to recognize the reality of teenage sexual activity is implicitly to endorse it.

Public health officials may have legitimate questions about the merits of HPV vaccine mandates, in light of the financial and logistic burdens these may impose on families and schools, and also may be uncertain about adverse-event rates in mass-scale programs. But given that the moral objections to requiring HPV vaccination are largely emotional, this source of resistance to mandates is difficult to justify. Since, without exception, the proposed laws permit parents to refuse to have their daughters vaccinated, the only valid objection is that parents must actively manifest such refusal. Such a slight burden on parents can hardly justify backing away from the most effective means of protecting a generation of women, and in particular, poor and disadvantaged women, from the scourge of cervical cancer. To lighten that burden even further, the governor of Virginia has proposed that refusals need not even be put in writing. Perhaps it is time for parents who object to HPV vaccinations to take a lesson from their children and heed the words of Nancy Reagan: Just say no.

Source Information

Professor Charo is a professor of law and bioethics at the University of Wisconsin, Madison.

An interview with Professor Charo can be heard at www.nejm.org.

References

1. Adolescent vaccination: bridging from a strong childhood foundation to a healthy adulthood. Bethesda, MD: National Foundation for Infectious Diseases, 2005. (Accessed April 19, 2007, at http://www.nfid.org/pdf/publications/adolescentvacc.pdf.)
2. Hodges J, Gostin L. School vaccination requirements: historical, social, and legal perspectives. Ky Law J 2001–2002;90:831-90.
3. Trenholm C, Devaney B, Fortson K, Quay L, Wheeler J, Clark M. Impacts of four Title V, Section 510 abstinence education programs: final report. Princeton, NJ: Mathematica Policy Research, April 2007. (Accessed April 19, 2007, at http://www.mathematica-mpr.com/publications/PDFs/impactabstinence.pdf.)
4. Dailard C. Legislating against arousal: the growing divide between federal policy and teenage sexual behavior. Guttmacher Policy Rev 2006;9:12-6.
5. Bleakley A, Hennessy M, Fishbein M. Public opinion on sex education in US schools. Arch Pediatr Adolesc Med 2006;160:1151-1156. [Free Full Text]

This article has been cited by otherarticles:

• Baden, L. R., Curfman, G. D., Morrissey, S., Drazen, J. M. (2007). Human Papillomavirus Vaccine -- Opportunity and Challenge. NEJM 356: 1990-1991 [Full Text]
• (2007). HPV Vaccination: Data at Last. JWatch General 2007: 1-1 [Full Text]

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HPV Vaccination — More Answers, More Questions | Editorial Published in New England Journal of Medicine on 5/10/07

Editorial
New England Journal of Medicine
Volume 356:1991-1993 May 10, 2007 Number 19

HPV Vaccination — More Answers, More Questions
George F. Sawaya, M.D., and Karen Smith-McCune, M.D., Ph.D.

The availability of a "cancer vaccine" has elicited enormous enthusiasm from the medical community and the public, culminating in advocacy for mandatory vaccination against human papillomavirus (HPV) and a recommendation from the Centers for Disease Control and Prevention (CDC) that 30 million girls and women between the ages of 11 and 26 years in the United States be vaccinated.1 Previous reports2,3 showed a remarkable 100% efficacy of a quadrivalent vaccine targeting HPV types 6, 11, 16, and 18 on outcomes related to vaccine HPV types in women with no evidence of previous exposure to those types. Since HPV types 16 and 18 are implicated in 70% of cervical cancers,4 these types are ideal targets for a new vaccine.

In this issue of the Journal, reports on two large, ongoing, randomized, placebo-controlled trials show the effect of this vaccine on important clinical outcomes, including rates of adenocarcinoma in situ and cervical intraepithelial neoplasia after an average of 3 years of follow-up.5,6 Investigators in these trials have hit their mark soundly: the vaccine showed significant efficacy against anogenital and cervical lesions related to vaccine type in women with no evidence of previous exposure to vaccine-specific types; the vaccine also appeared to be safe. In addition, the studies report outcomes in all subjects regardless of HPV status at baseline and regardless of whether outcomes were related to HPV types targeted by the vaccine. Policymakers now have more evidence to assess the benefits and risks of widespread vaccination.

Given the rarity of incident cervical cancer, preinvasive cervical lesions with high invasive potential are used in contemporary studies as surrogate outcomes for cervical cancer. Adenocarcinoma in situ is a rare lesion widely considered to be a precursor of cancer. Cervical intraepithelial neoplasia is graded from 1 to 3 on the basis of histopathological criteria. Grade 1 cervical intraepithelial neoplasia indicates the presence of active HPV infection and is not considered to be precancerous; current guidelines discourage treatment of this condition.7,8 Grade 2 cervical intraepithelial neoplasia is treated in most women but is not an irrefutable cancer surrogate, since up to 40% of such lesions regress spontaneously9; current guidelines suggest that some young women with such lesions do not need to be treated.7,8 Grade 3 cervical intraepithelial neoplasia, on the other hand, has the lowest likelihood of regression and the strongest potential to be invasive. The Food and Drug Administration (FDA) considers grade 2 and 3 cervical intraepithelial neoplasia and adenocarcinoma in situ to be acceptable surrogate outcomes for cervical cancer; other observers consider grade 3 cervical intraepithelial neoplasia and adenocarcinoma in situ to be more appropriate surrogates.9

In these trials, called Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I and II, what is the efficacy of vaccination among all subjects, regardless of causal HPV types? In the FUTURE I trial,5 rates of grades 1 to 3 cervical intraepithelial neoplasia or adenocarcinoma in situ per 100 person-years were 4.7 in vaccinated women and 5.9 in unvaccinated women, an efficacy of 20%. Analyses by lesion type indicate that this reduction was largely attributable to a lower rate of grade 1 cervical intraepithelial neoplasia in vaccinated women; no efficacy was demonstrable for higher-grade disease, but the trial may have lacked adequate power to detect a difference. Vaccinated women also had lower rates of external anogenital and vaginal lesions (1.3 vs. 2.1). In the larger FUTURE II trial,6 rates of grade 2 or 3 cervical intraepithelial neoplasia or adenocarcinoma in situ were 1.3 in vaccinated women and 1.5 in unvaccinated women, an efficacy of 17%. In analyses by lesion type, the efficacy appears to be significant only for grade 2 cervical intraepithelial neoplasia; no efficacy was demonstrable for grade 3 cervical intraepithelial neoplasia or adenocarcinoma in situ.

What can be inferred from these data about the potential effect of vaccination on populations that include sexually active women? In the FUTURE II trial, 93% of subjects were nonvirgins. With grade 2 or 3 cervical intraepithelial neoplasia or adenocarcinoma in situ as the outcome, the difference in risk so far appears to be modest: 219 of 6087 vaccinated women (3.6%) received this diagnosis over an average of 3 years, as compared with 266 of 6080 unvaccinated women (4.4%). The absolute risk difference of 0.8% indicates that 129 women would need to be vaccinated in order to prevent one case of grade 2 or 3 cervical intraepithelial neoplasia or adenocarcinoma in situ occurring during this period. If grade 3 cervical intraepithelial neoplasia or adenocarcinoma in situ were the most relevant outcome, evidence was insufficient to infer the effectiveness of vaccination.

Why is vaccine efficacy modest in the entire cohort? One factor is the apparent lack of efficacy among subjects with evidence of previous exposure to HPV types included in the vaccine. The FUTURE II trial showed no effect of vaccination up to month 12, perhaps owing either to preinvasive lesions or to vaccine-type HPV infections that were present at enrollment. Therefore, vaccination before the onset of sexual activity seems to be preferable. In contrast to the CDC's guidelines, the American Cancer Society does not recommend universal vaccination among women between 18 and 26 years of age, citing probable diminished vaccine efficacy as the number of lifetime sexual partners increases.10 Trial outcomes stratified by risk factors that are strong surrogates for HPV exposure and are readily obtained clinically (e.g., the number of lifetime sexual partners) may prove to be useful in the future development of guidelines.

Another factor explaining the modest efficacy of the vaccine is the role of oncogenic HPV types not included in the vaccine. At least 15 oncogenic HPV types have been identified,4 so targeting only 2 types may not have had a great effect on overall rates of preinvasive lesions. Findings from the FUTURE II trial showed that the contribution of nonvaccine HPV types to overall grade 2 or 3 cervical intraepithelial neoplasia or adenocarcinoma in situ was sizable. In contrast to a plateau in the incidence of disease related to HPV types 16 and 18 among vaccinated women, the overall disease incidence regardless of HPV type continued to increase, raising the possibility that other oncogenic HPV types eventually filled the biologic niche left behind after the elimination of HPV types 16 and 18. An interim analysis of vaccine trial data submitted to the FDA11 showed a disproportionate, but not statistically significant, number of cases of grade 2 or 3 cervical intraepithelial neoplasia related to nonvaccine HPV types among vaccinated women. Updated analyses of data from these ongoing trials will be important to determine the effect of vaccination on rates of preinvasive lesions caused by nonvaccine HPV types.

What can be inferred from these data about the potential effect of vaccination among girls 11 and 12 years of age? The FUTURE trials did not enroll subjects in this age group. Within both trials, subgroups of subjects with no evidence of previous exposure to relevant vaccine HPV types were evaluated separately for vaccine efficacy. In these subgroups, efficacy of nearly 100% against all grades of cervical intraepithelial neoplasia and adenocarcinoma in situ related to vaccine HPV types was reported in both trials. However, it would be important to know the overall rates of grade 2 or 3 cervical intraepithelial neoplasia or adenocarcinoma in situ regardless of HPV types. Without these data, it is difficult to infer both the effectiveness of vaccination and the role of nonvaccine HPV types in overall rates of preinvasive lesions.

What do these results mean for cervical-cancer screening? Screening should continue in all vaccinated women, given the cumulative lifetime risk of exposure to other oncogenic HPV types and the unknown duration of anti-HPV immunity. The effect of vaccination on cervical cytologic findings was not reported in either trial, but if vaccination reduces the rates of abnormal findings, this benefit would be important. Of note, a trial of a monovalent HPV-16 vaccine reported no effect on cytologic abnormalities.12

Policymakers, clinicians, and parents have a keen sense of urgency about HPV vaccination. On one hand, the vaccine has high efficacy against certain HPV types that cause life-threatening disease, and it appears to be safe; delaying vaccination may mean that many women will miss an opportunity for long-lasting protection. On the other hand, a cautious approach may be warranted in light of important unanswered questions about overall vaccine effectiveness, duration of protection, and adverse effects that may emerge over time. HPV vaccination has the potential for profound public health benefit if the most optimistic scenario of effectiveness is realized.

No potential conflict of interest relevant to this article was reported.

Source Information

From the Departments of Obstetrics, Gynecology and Reproductive Sciences (G.F.S., K.S.-M.), Epidemiology and Biostatistics (G.F.S.), and the Comprehensive Cancer Center (G.F.S., K.S.-M.), University of California, San Francisco, San Francisco.

References

1. Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER. Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56:1-24. [Medline]
2. Villa LL, Costa RL, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 2005;6:271-278. [CrossRef][ISI][Medline]
3. Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer 2006;95:1459-1466. [CrossRef][ISI][Medline]
4. Munoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518-527. [Free Full Text]
5. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med 2007;356:1928-1943. [Free Full Text]
6. The FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007;356:1915-1927. [Free Full Text]
7. Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;287:2120-2129. [Free Full Text]
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This article has been cited by other articles:

* Baden, L. R., Curfman, G. D., Morrissey, S., Drazen, J. M. (2007). Human Papillomavirus Vaccine -- Opportunity and Challenge. NEJM 356: 1990-1991 [Full Text]
* (2007). Efficacy and Safety of the Quadrivalent HPV Vaccine. JWatch Infect. Diseases 2007: 1-1 [Full Text]
* (2007). HPV Vaccination: Data at Last. JWatch General 2007: 1-1 [Full Text]


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New Evidence Shows Cervical Cancer Vaccine Works

Out ten-gallon hats are off to Dallas/Ft. Worth CBS affiliate 11 TV for this report on an issue that remains "controversial" in the Lone Star State.

(CBS News) The latest clinical trials on the new vaccine that guards against the virus that causes most cases of cervical cancer hold good news for girls and women who've taken it or may take it, and for its manufacturer.

Early Show medical correspondent Dr. Emily Senay explains that Merck's Gardasil is meant to fight off certain strains of human papilloma virus (HPV), which is known to cause cervical cancer.

Though it remains controversial, there's fresh research that Gardasil is effective in fighting off HPV, Senay says, and the news appears to provide even more reason for young girls to be vaccinated, as the federal Centers for Disease Control and Prevention (CDC) and other experts recommend.

HPV is spread through sexual contact, and the strains the vaccine wards off are responsible for about 70 percent of cervical cancer cases, so getting vaccinated can significantly lower a woman or girl's risk of developing the cancer, Senay continues.

Early studies of the vaccine showed it to be so valuable in fighting cervical cancer that the Food and Drug Administration (FDA) gave it fast track approval last June.

Clinical trials continued, Senay points out, to confirm that everything was as it should be, and apparently, it is.

Among previously uninfected patients who received the vaccine, the protection rate after three years was 98 percent, according to results published in the New England Journal of Medicine. So the strains of the virus that account for seven-in-ten cervical cancer cases were effectively stymied.

The CDC recommends vaccination for all girls 11- and 12-years-old. Girls as young as nine are eligible to receive it. Girls and women from age 13 to 26 are also urged to get it, if they still haven't been vaccinated.

The exception to those guidelines involves women who are pregnant. They should wait until after the baby is born to be vaccinated.

The younger a woman or girl is, Senay notes, the greater the chance she isn't already infected with HPV. It's simple probability: The older she is, the more sexual encounters she is likely to have had, and the more opportunities she has had to contract the virus.

Senay stresses that the vaccine does nothing against infections that are already present. Its effectiveness is for patients who are virus-free. So, getting vaccinated while it's still early enough for the vaccine to do some good is important.

The age of the girls involved, and the connection of the vaccine to sexual activity, are contributing to an ongoing controversy over whether states and localities should mandate that they get Gardasil.

Senay also observed that, if a woman is vaccinated before she's sexually active, or at least before she's infected, she still can't be worry-free about getting cervical cancer. Roughly 30 percent of cervical cancers come from strains of HPV that are not diminished by this vaccine. So, no one should let her guard down.

The American Cancer Society recommends cervical cancer screening, including a pap test, within three years of a woman's first intercourse, or by age 21, whichever comes first.

Depending on the kind of pap test used, screening should continue either annually or every-other year.

After age 30, if tests haven't detected a problem, they can be spaced out even more. After age 30, women can also combine their pap tests with a second test that specifically detects the presence of HPV.

The bottom line is to keep getting screened, because there's still a risk of developing the cancer. But all signs point to that risk diminishing sharply, if girls or young women have been vaccinated.

Researchers are not surprised by the new data. Early studies of the cervical cancer vaccine showed it to be so valuable in the prevention of cervical cancer that the Food and Drug Administration (FDA) gave it fast track approval last June.
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Florida Ignorance Lobby Wins Battle Over Cervical Cancer Education

Marking a victory for the ignorance, suffering, and death lobby in Florida, lawmakers in The Sunshine State ended their regular session without passing a bill that would have required that information be provided to schoolgirls about the cervical cancer vaccine and how they may protect themselves from the disease that is as deadly as it is preventable.

The measure initially was to require cervical vaccination, but was "softened" only to require that information be given out about the human papillomavirus and its link to cervical cancer.

Evidently, there is a powerful lobby in Florida of those so strongly in favor of subjecting girls to suffering and premature death from cervical cancer that they will not settle just at preventing compulsory cervical cancer vaccination. They feel so strongly about knowingly and necessarily subjecting a certain percentage of girls to cervical cancer later in life that they have prevented information about the vaccine from being disseminated.

I suppose they fear that girls and young women (and/or their parents) could use information about cervical cancer prevention to make make educated choices for themselves as to whether they want the cervical cancer vaccine. The choice overwhelmingly may be "yes."

What's next with these people? Overturn the 19th Amendment to the U.S. Constitution and revoke womens' right to vote? Take away womens' right to own property.

I am not aware of any of these types being around when the polio vaccine was introduced.

Can anyone explain to me how these people's position reflects anything other than incredibly deep-seated misogyny? If so, please do.
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National Cervical Cancer Coalition Launches Online Support Network Tool For Cervical Cancer And HPV Community

The National Cervical Cancer Coalition (NCCC) is the nations oldest nonprofit organization exclusively focused on working with women, family members and friends that are battling issues related to cervical cancer and HPV disease.

The National Cervical Cancer Coalition (NCCC) announces the launch of a new online support network with ClincaHealth. The aim of this online community is to foster peer-to-peer communication and information sharing about cervical cancer and the humanpapilomavirus (HPV) including prevention, detection and treatments via the web. It is designed to be the meeting place for anyone desiring to connect with others interested in or affected by cervical cancer/HPV - survivors, those at risk, family, friends, clinicians, educators and the public at large. "With this community tool, the NCCC sets to become the center of online discussions related to cervical cancer and HPV," stated Sarina Araujo, executive director of NCCC.

National Cervical Cancer Coalition
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Status of Texas Cervical Cancer Bill Uncertain

Texas Gov. Rick Perry wouldn't say Wednesday whether he'll veto a bill the Legislature approved last week that blocks state officials from following his anti cervical cancer vaccine mandate.

But he stood by his decision to issue the executive order, saying it prompted an international debate and raised awareness of cervical cancer.
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More Cervical Cancer Vaccine Politics

"Is Forcing the HPV Vaccine on Girls a Violation of Their Rights? Parents, Doctors Weigh In"

The above article was posted today at blackamericaweb.com. Dr. Danuej,cervical cancer vaccination from a civil rights perspecitve.
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