HPV vaccination and the prevention of cervical cancer: a paradigm changing event

It is difficult to overstate the importance of data regarding the striking effectiveness of two different human papillomavirus vaccination strategies as a rational approach to prevent the development of cervical cancer. Available information about the vaccines reveals that, assuming a young woman has not previously been exposed to the specific HPV viruses included in either the bivalent or quadrivalent vaccine preparations and that she completes the planned vaccination schedule, the vaccination strategy is nearly 100% effective in preventing persistent infection. This is a recognized, essentially absolute, requirement for the subsequent development of this malignancy.

Further, the admittedly “early data” strongly suggest that this profoundly effective approach to blocking the establishment of persistence of the virus and incorporation of the viral DNA into the human genome prevents future premalignant and malignant lesions in the cervix. Due to the recognized decade-plus latency period between HPV infection and cancer, it will be many years before it will be possible to make a definitive statement for patients who participated in these trials regarding the ultimate major protective effect of vaccination on the subsequent development of invasive cervix cancer. However, the existing data are strongly supportive of the hypothesis that this conclusion will be warranted.

Maurie Markman

Impact of vaccine

It is also critical to acknowledge the realistic potential for a truly profound impact of HPV vaccination on certain populations, particularly within the developing world. Although it is estimated that invasive cervical cancer will be diagnosed in a relatively modest number of women in the United States each year (approximately 11,000), worldwide 500,000 new cases will be detected each year resulting in more than 250,000 deaths.

In addition, when one considers the lack of facilities (including radiation oncology units), cancer specialists (including trained gynecologic oncologists), and pharmaceuticals (including most prominently the frequently needed narcotic analgesic medications) in many countries, the potentially horrifying impact of the disease is substantially magnified. It is also important to appreciate that even in the United States there are specific subgroups of women who may be particularly vulnerable to the development of cervical cancer (eg, populations without access to routine preventive medical care, including gynecologic examinations with the performance of a pap smear).

Despite the demonstrated effectiveness of HPV vaccination, a number of important questions and difficult issues remain unresolved. These include:

What is the duration of the effectiveness of the vaccine and will revaccination be required?

Although a definitive answer to this question is not currently available, current data demonstrate that after vaccination, protective HPV antibody titers appear to persist for more than five years. As the originally vaccinated patient populations who participated in clinical trials are followed, with measurement of antibody levels, critically relevant information will become known regarding the adequacy of these levels that will inform future public health recommendations for the need of a booster revaccination strategy.

However, it is critical to clearly state that the absence of data regarding this issue should absolutely not prevent or delay the recommendation for vaccination of young women who have been documented to benefit from this cancer prevention strategy.

What can be done about preventing the 30% of cervix cancers not involving HPV 16 or 18?

Although approximately 70% of cervical cancer worldwide is caused by HPV 16 or 18, the major components of the two extensively tested HPV vaccines, the remaining 30% are caused by a large number of other types that appear to vary greatly based on particular locations. It is possible that future vaccine preparations may add components related to HPV viruses within specific geographic areas. There is also the potential that a clinically relevant element of cross reactivity and protection against cancer induced by non-16/18 HPV types will be documented during future follow-up of the currently vaccinated populations.

Can the cost of HPV vaccination be reduced?

Cost of the HPV vaccines is a major issue, both among populations in the United States without adequate insurance coverage and in the developing world. It is hoped that funding for HPV vaccination will be considered a priority for local, state, national public health organizations and for philanthropy.

Competition among vaccine providers and innovative, more cost-effective approaches for the manufacture of antiviral vaccines may also reduce the costs of vaccination strategies. The concept of a single-dose or sustained-release vaccine would have the potential to simplify administration and reduce the level of resources required for an effective vaccination program.

Should the HPV vaccine be administered to males?

It is unquestionable that the administration of HPV vaccine to young men would improve the overall effectiveness of vaccination for the prevention of persistent viral infection in women.

However, this fact alone would appear to be insufficient justification to advocate a public health strategy that includes routine vaccination of all young boys. However, impressive epidemiological data have now revealed the importance of persistent HPV infection in the development of cancers of the head and neck and anogenital regions. It is reasonable to speculate that vaccination of both males and females will reduce the risk of HPV-associated cancers in these areas similar to the documented utility of this approach for cervical cancer. Future studies will hopefully provide data that permit a definitive answer to this question.

What is the overall risk of serious toxicity associated with HPV vaccination?

Existing data demonstrate the two extensively tested HPV vaccine approaches to be very safe. Although unconfirmed reports suggested a somewhat concerning risk of hypersensitivity reactions resulting from vaccination, thorough evaluation by one group revealed that only 10% of such reported events are actually due to a confirmed allergy. Although extended follow-up of the currently vaccinated population will be required to document if there are any long-term side effects of the HPV vaccines, to date no serious delayed toxicities have been confirmed to be caused by these products.

Finally, it must be noted that much of the controversy surrounding HPV vaccination has absolutely nothing to do with the utility of this innovative cancer prevention strategy, but rather focuses on the fact that HPV is a sexually transmitted infectious disease. It is critical that health care providers and educators continue to emphasize the documented major value of this approach to both reduce the risk for the development of a potentially serious cancer and the clinically relevant morbidity, as well as intense anxiety associated with the diagnosis and treatment of this condition.

Maurie Markman, MD, is vice president for clinical research and serves in the department of gynecologic medical oncology at The University of Texas M.D. Anderson Cancer Center. He is also a member of the HemOnc Today Editorial Board.

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