© 2004 by Oxford University Press
© 2004 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Human Papillomavirus in Oral Exfoliated Cells and Risk of Head and Neck Cancer
Affiliation of authors: Department of Epidemiology, College of Public Health (EMS), VAMC and Department of Pathology, Carver College of Medicine (THH, LPT), University of Iowa, Iowa City
Correspondence to: Elaine M. Smith, PhD, MPH, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242 (e-mail: elaine-smith{at}uiowa.edu)
Dr. Castle’s caution regarding human papillomavirus high-risk (HPV-HR) types in head and neck cancer is, in our opinion, unduly pessimistic. Although he recognizes that our oral HPV testing was more accurate for the detection of head and neck cancer (HNC), he lumps our results (1) with those of a study by the IARC consortium (2) that reported lower HPV-HR prevalence in case and control subjects alike. We believe that combining the results (his table 1) is misleading in its interpretation because the IARC study concerned a different population and used different specimen collection and HPV evaluation methods. We overcame some of the limitations of HPV detection with improved sample collection and by monitoring the nucleated cell count in each cytology specimen with a hemocytometer. Consequently, 99.1% of our oral rinses were adequate for PCR compared with 43.6% in (2).
HPV-HR–associated cancers and HPV-HR infection in the head and neck area in general are more common than the 25% HPV-positive tonsillar and oropharyngeal cancers stated by Dr. Castle. Whereas the IARC study (2) reported 18% HPV-HR–positive HNCs in these sites, we (1) and Gillison and Shah (3) reported 38% and 57%, respectively. We identified HPV-HR–positive tumors among non–squamous-cell histologic types of HNC and at oral cavity sites other than the tonsils or the oropharynx (1). Association with HPV-HR infection is therefore not limited to squamous-cell carcinoma or to tumor sites in the tonsillar area or oropharynx. We believe that an oral rinse has a greater potential for including HPV-HR–infected cells from the entire oral cavity and oropharynx than targeted scrapes or biopsies that can examine only localized areas and would miss a neighboring focus of HPV-infected or HPV-positive cancer cells. Our experience is in agreement with the findings of Lawton et al. (5), who reported consistent cytology specimen collection using oral rinses.
Although HPV type 16 (HPV16) is the most common HPV-HR type in HNC, it is not unique: We and others (1–4) have identified other cervical cancer–causing HPV-HR types in HNC. Indeed, we used laser-directed microdissection to isolate the tumor tissue and confirmed, by DNA sequencing, the HPV type in tumors that were located outside of the tonsils or oropharynx and in those harboring a virus type other than HPV16 (1). It is apparent that HPV16 is more common in HPV-positive cancers in the head and neck (up to 85%) than in the cervix (
50%). It will be interesting to determine whether keratinocytes from the oral cavity, tonsillar fossa, or oropharynx exhibit different susceptibilities to infection with and establishment of persistence by different HPV-HR types.
Finally, Dr. Castle raises conceptual concerns regarding HPV detection as a biomarker of HPV-associated HNC. He states that, compared with cervical cancer, the strength of the association between HPV-HR infection and HPV-HR–positive HNC is weakened by a lower concordance between oral HPV status and HPV positivity of the tumor. We discussed possible limitations of HPV-HR detection in oral rinses (1). HPV-HR DNA in oral cytology specimens may come from HPV-positive cancer cells, cells from the HPV-infected field in which the HPV-associated tumor arose, or from an independent infection with the same or another HPV-HR type. Nevertheless, the detection of even an unrelated HPV-HR type in the oral cavity may identify individuals who are more susceptible to infection because of their limited immunologic ability to eliminate the virus or other unknown causes. This approach thus broadens the captured group of individuals at risk and would be predicted to encompass those with Fanconi anemia (6,7), as Dr. Castle suggests, or possibly with other diseases affecting genome maintenance. We disagree that this decreases the value of HPV-HR detection as a potential biomarker for HPV-associated HNC. Clearly, most cigarette smokers do not develop lung cancer, yet smoking is a significant risk factor and predictor of those who are more likely to develop lung cancer in their lifetimes. Likewise, we argue that, on the basis of our findings, people with a detectable HPV-HR–type infection may be at an increased risk of developing an HPV-HR–associated HNC, a deadly disease for which no screening or early diagnostic tests are currently available. Thus, we believe that data from our laboratory and others warrant further exploration of HPV detection as a biomarker for the identification of individuals who are at risk of developing an HPV-associated cancer of the head and neck.
REFERENCES
1 Smith EM, Ritchie JM, Summersgill KF, Hoffman HT, Wang DH, Haugen TH, et al. Human papillomavirus in oral exfoliated cells and risk of head and neck cancer. J Natl Cancer Inst 2004;96:449–55.
2 Herrero R, Castellsague X, Pawlita M, Lissowska J, Kee F, Balaram P, et al. Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst 2003;95:1772–83.
3 Gillison ML, Shah KV. Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers. Curr Opin Oncol 2001;13:183–8.[CrossRef][Web of Science][Medline]
4 Schwartz SM, Daling JR, Doody DR, Wipf GC, Carter JJ, Madeleine MM, et al. Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J Natl Cancer Inst 1998;90:1626–36.
5 Lawton G, Thomas S, Schonrock J, Monsour F, Frazer I. Human papillomaviruses in normal oral mucosa: a comparison of methods for sample collection. J Oral Pathol Med 1992;21:265–9.[CrossRef][Web of Science][Medline]
6 Lowy DR, Gillison ML. A new link between Fanconi anemia and human papillomavirus-associated malignancies. J Natl Cancer Inst 2003;95:1648–50.
7 Kutler DI, Wreesmann VB, Goverdhan A, Ben-Porat L, Satagonpan J, Ngai I, et al. Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients. J Natl Cancer Inst 2003;95:1718–21.
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J Natl Cancer Inst 2004 96: 1181-1182.
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