Are we closer to the prevention of HPV-related diseases?(human papillomavirus)

Background and cost burden of HPV infection

Human papillomavirus (HPV) infects squamous and glandular epithelial tissues. Noncancerous hand and plantar warts (HPV types 1, 2, and 4) as well as flat warts (HPV types 3 and 10) are common in almost all people. Butcher's warts (HPV types 2 and 7) occur in 70% of meat handlers, and genital warts (HPV types 6 and 11) occur in more than 1 million people per year; and will infect approximately 75% of the US population over their lifetime. (1,2) Periungual warts (HPV types 16 and 18) around the fingernail bed develop into squamous carcinomas in approximately 1% of those infected. (3,4) Oral warts (HPV types 6 and 11) and focal epithelial hyperplasia (HPV types 13 and 32), or Heck's Disease, are almost always benign, whereas 20% to 40% of mouth, throat, tongue, and lung cancers, much more rare, are associated with HPV types 16 and 18. (5) Likewise, esophageal warts, and both squamous and glandular esophageal cancers, occur in about 3% of the population (HPV types 6, 16, 18, 66, and 52), and 40% of conjunctival papillomas and carcinomas (HPV types 6, 11, 16, and 18) are caused by HPV infections. (6-10)

HPV is a significant medical burden worldwide. Although infection with low-risk HPV types 6 and 11 causes medically benign cervical, vaginal, vulvar; anal, penile, scrotal, and perineal warts, persistent infection with high-risk, oncogenic types 16 and 18 can cause a number of epithelial cancers. Approximately 10,000 women are diagnosed with cervical cancer, 2160 women are diagnosed with vaginal, 2000 women are diagnosed with vulvar, 1400 men are diagnosed with anal, 1100 men are diagnosed with penile, and 500 men are diagnosed with scrotal cancers each year. (11-15) This year, the National Toxicology Program recognized the body of evidence that has accumulated over the past 10 years and declared HPV an official carcinogen that is as dangerous as asbestos. (16)

The cost of HPV infection can be classified by the milestones of infection. These include diagnosis of genital or cervical HPV infection, cervical cytology or HPV DNA testing, and treatment. A second stratification of costs for both infection and cancer occurs across organ sites and includes cervical, vaginal, penile, scrotal, and anal sites. DNA screening for high-risk HPV types, with tests such as Hybrid Capture 2 (Digene, Gaithersburg, MD), is reserved for cases where cytologic changes have been observed. Since HPV infection can be subclinical, identifying people at risk can be problematic, and while there is no treatment for subclinical HPV, the costs of testing are usually attributed to patient demand for knowledge that may affect their quality of life or future. These total costs cause a considerable health burden in the United States.

Costs for HPV diagnosis and treatment, in the disease's warty form, include the costs of a visual clinical exam, often with bright light, magnification, and 5% acetic acid application on any of the anogenital sites, and have been estimated to cost approximately $400 per incident case. Many of the wart diagnoses in women are made as a consequence of an abnormal Papanicolaou (Pap) test, whereas all of the wart diagnoses in men are visually detected by either self-exam or physician-directed examination. The incidence of anogenital wart disease in the United States is approximately 1.7 to 2 cases per 1000, with costs exceeding $160 million annually for the adult US population. (17,18) These costs do not include those of the self-applied medications, obtained from pharmacies, that are often used for genital wart treatment.

The cervical cancer screening program of repeated Pap tests, adopted in the United States for detecting dysplasia and other grades of cervical lesions, is the only standardized longitudinal screening system for predictive cancer detection. As it exists, screening alone reaches a cervical cancer prevention threshold of 2 to 3 of every 100,000 women. (19) Despite the excellence of the Pap test to detect squamous cell carcinoma of the cervix, early cervical changes from HPV infection of the squamous and glandular cervical epithelium are not always reproducible or predictive of cervical cancer. (20) This means that there will always be women who are screened, yet who develop cervical cancer; and there will always be a large number of women whose cervical cytology results are interpreted as abnormal, in the absence of clinical disease. Insinga et al (21) recently estimated that while 0.4% of all Pap tests showed HPV infection, 2.4% were false positive, 0.5% revealed cervical cancer precursors, and 0.02% were indicative of invasive cancer. The costs of follow-up for false-positive cases constituted nearly 25% of all cervical cancer screening costs but did not take into account the discomfort, inconvenience, psychologic distress, and time costs women additionally experience.

Overall,…