"Halfway Technology": Is It Time to Seriously Discuss Transitioning From the Current Focus of Cancer Research?

Maurie Markman, MD

It was more than 50 years ago in his elegant lay book, The Lives of a Cell, that the late eminent physician-scientist, administrator, and author Lewis Thomas described rather starkly and quite accurately the particular focus of both clinical medicine and clini- cal investigation over the succeeding decades, including within the domain of cancer management.1

In a chapter titled “The Technology of Medicine,” Thomas defines the term halfway technology, which “represents the kinds of things that must be done after the fact, in efforts to compensate for the incapacitating effects of certain diseases whose course one is unable to do much about. It is a technology designed to make up for disease, or to postpone death.”1

Thomas adds, specifically as related to cancer: “Much of what is done in the treatment of cancer by surgery, irradiation, and chemotherapy represents halfway tech- nology, in the sense that these measures are directed at the existence of already established cancer cells, but not at the mechanisms by which cells become neoplastic.”1

He then continues by acknowledging a different type of technology, “the kind that is so effective that it seems to attract the least public notice; it has come to be taken for granted. This is the genuinely decisive technology of modern medicine, exemplified best by modern methods for immunization....” Finally, Thomas concludes, “The point to be made about this kind of technology—the real high technology of medicine—is that it comes as the result of genuine understanding of disease mechanisms, and when it becomes available, it is relatively inexpensive and relatively easy to deliver.”

Simply remarkable. Although written 50 years ago, it might have been written yesterday in a description of the role of human papillomavirus (HPV) in the pathogene- sis of cervix cancer and the objectively realistic opportunity for vaccination to prevent almost all cases worldwide.1

Before proceeding, a disclaimer is required. What follows is a brief discussion of the potential to realign much of the current focus of cancer research from the treatment of established advanced cancers to what Thomas calls the “real technology of medicine.” However, to be clear, there is no intent here to denigrate the tremendous efforts of countless individuals; academic institutions; and pharmaceutical, device, and diagnostic companies who have devoted careers and enormous financial resources to improving the quantity and quality of lives of patients diagnosed with or progressing to this challenging clinical state. (To avoid even the suspicion of intent to criticize any indi- vidual, group, or organization, references to specific research efforts or products will not be included in what follows.)

In the case of advanced/metastatic cervix cancer, cisplatin-based systemic therapy has been known for several decades to be of modest and short-lived clinical utility, but impressively, when the cytotoxic agent was delivered concurrently with external beam radiation, survival of locally advanced disease was revealed to be improved. More recently, the introduction of several immunotherapeutic strategies has been documented to favorably affect outcomes in the setting of advanced disease.2 However, despite these unquestionably clinically meaningful effects of antineoplastic therapy, oncologists who care for women discovered to have metastatic or regional spread of cervix cancer at diagnosis or whose condition ultimately progresses to this clinical state appreciate just how devastating this malignancy can be. This includes the profound effect on quality of life even where curative therapy is attempted.2

Again, fully recognizing the past and current extraordinary efforts of researchers and clinicians in this specific clinical arena, the intent of the current discussion is to briefly highlight the role of HPV vaccination in the prevention of cervix cancer and other documented HPV-associated malignancies and to challenge the medical and public health communities to seek to prioritize efforts toward this strategy.

In the opinion of this commentator, it is difficult to overstate the existing evidence for both the documented efficacy of HPV vaccination undertaken prior to sexual debut in preventing persistent infection with the potentially carcinogenic virus and the well-established short- and long-term safety profile of the available vaccination products employed in the setting of clinical trials and real-world noninvestigative usage.

Several reports of large, well-designed, and conducted randomized trials, as well as real-world population-based analyses, have demonstrated a substantial reduction in the incidence of known cancer precursors. Further, more recently reported data from several countries have confirmed a major effect on the incidence of documented cases of invasive cervical cancer among individuals who have received HPV vaccination.3-6

Importantly, this includes outcomes in both the developed and developing worlds. Yet despite these impressive safety and efficacy data, existing evidence suggests HPV vaccination rates remain far less than optimal in the United States,7 including, remarkably, among young cancer survivors.8

There are undoubtedly many reasons for this outcome, including vaccine fears, lack of sufficient time for clinicians to provide essential data and respond to questions regarding the safety and clinical utility of HPV vaccination, and uncertain effectiveness in general of existing communication strategies employed to deliver the message to decision-makers who in most situations are the individual’s parents.

Can we overcome these issues to increase the delivery of this remarkably safe and effective cancer prevention vaccination strategy? Restated, employing the terminology of Thomas: How long will we (or, perhaps correctly, can we) continue to so heavily focus our efforts on “halfway technology” in cervix cancer (and other malignancies where HPV has a critical causative role) vs the known beneficial HPV vaccine in this clinical setting, the “real high technology of medicine?”