Correspondence
Human Papillomavirus Infection as a Risk Factor for Squamous-Cell Carcinoma of the Head and Neck
N Engl J Med 2001; 345:376-377August 2, 2001
- Article
To the Editor:
Mork et al. (April 12 issue)1 suggest that infection with human papillomavirus type 16 (HPV-16) may be a risk factor for squamous-cell carcinoma of the head and neck. Other studies have shown that rates of HPV infection are higher in patients with human immunodeficiency virus (HIV) infection than in the healthy population2 and that the incidence of anogenital cancer is increased in people with HIV infection or AIDS. An increased incidence of squamous-cell carcinoma of the head and neck and other possible HPV-associated cancers, such as esophageal squamous-cell carcinoma, might also be expected in patients with HIV infection or AIDS. However, no such finding has been reported,3 which suggests that HPV-16 infection (recognized by seropositivity for HPV-16) is not necessarily related to the development of squamous-cell carcinoma of the head and neck. Anti-HPV antibodies might simply be the sign of an infection that had been eradicated long before the cancer began to evolve.
3 ReferencesJosé Mario Sabio, M.D.
Juan Pasquau, M.D.
Juan Jiménez-Alonso, M.D.
Virgen de las Nieves University Hospital, 18012 Granada, Spain
jualso@hvn.sas. cica. es 1
Mork J ,Lie AK ,Glattre E , et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 2001;344:1125-1131
Full Text | Web of Science | Medline2
Palefsky JM ,Holly EA ,Ralston ML ,Jay N . Prevalence and risk factors for human papillomavirus infection of the anal canal in human immunodeficiency virus (HIV)-positive and HIV-negative homosexual men. J Infect Dis 1998;177:361-367
CrossRef | Web of Science | Medline3
Lacoste D ,Dabis F ,Boulogne N ,Labouyrie E ,Merlio JP . Cancer incidence in a cohort of human immunodeficiency virus seroconverters. Cancer 1998;82:996-998
CrossRef | Web of Science | Medline
To the Editor:
Mork et al. report an increased risk of squamous-cell carcinoma of the head and neck in HPV-16–seropositive subjects. It is known that in the normal population, the rate of anogenital infections and the seroprevalence of HPV-16 antibodies are higher among females than among males (seroprevalence, 12 percent vs. 3 percent),1 whereas squamous-cell carcinoma of the head and neck develops more frequently in males.2 We wonder why Mork et al. did not stratify the risk estimates according to sex; the results would provide information on the confounding effect of anogenital infections.
2 ReferencesJens Peter Klussmann, M.D.
Soenke Weissenborn, M.S.
Pawel G. Fuchs, M.D., Ph.D.
University of Cologne, 50921 Cologne, Germany
peter.klussmann@uni-koeln. de 1
Strickler HD ,Kirk GD ,Figueroa JP , et al. HPV 16 antibody prevalence in Jamaica and the United States reflects differences in cervical cancer rates. Int J Cancer 1999;80:339-344
CrossRef | Web of Science | Medline2
Vokes EE ,Weichselbaum RR ,Lippman SM ,Hong WK . Head and neck cancer. N Engl J Med 1993;328:184-194
Full Text | Web of Science | Medline
To the Editor:
In the study by Mork and colleagues, 35 of 292 patients (12 percent) with head and neck cancers were seropositive for HPV-16, as compared with 102 of 1568 matched controls (7 percent). It is not entirely clear what the authors mean by stating that HPV-16 is a risk factor for squamous-cell carcinoma of the head and neck. Table 2 shows that of a cohort of 1860 persons (292 persons with squamous-cell carcinoma and 1568 matched controls), 137 persons had at one time been seropositive for HPV-16. In only 35 of these persons (26 percent) did a carcinoma develop. Therefore, HPV-16 infection cannot be said to be a reliable predictor of the subsequent occurrence of a carcinoma in the head and neck region.
If the matched controls were representative of the entire cohort of almost 900,000 persons, 7 percent of the cohort (approximately 63,000 persons) would be seropositive for HPV-16. If we include HVP-18, a total of 117,000 persons would be seropositive. How could the relatively few persons in whom a cancer would later develop be identified from this large number, and how would it be possible to determine at what site (the anogenital region, the head and neck, or other region) a subsequent carcinoma would appear?
Jon Sudbø, D.D.S., M.D., Ph.D.
Norwegian Radium Hospital, 0310 Oslo, Norway
jon.sudbo@rh. uio. no Author/Editor Response
The authors reply:
To the Editor: Sabio et al. state that an increased incidence of head and neck cancer in patients with AIDS has not been reported. In the largest study to date of HPV-associated cancers in patients with HIV infection or AIDS, Frisch et al.1 did in fact find a significantly increased relative risk of tonsillar cancer among males with HIV infection or AIDS (relative risk, 2.6). That anogenital and head and neck cancers might share the same, transmissible cause is also indicated by the increased risk of oropharyngeal cancers among husbands of women with a history of cervical neoplasia.2 Sabio et al. also point out that HPV-16 seropositivity could reflect a previous HPV infection that had been eradicated long before the cancer began to evolve. This is why our study included an analysis by the polymerase chain reaction of HPV-16 DNA in subsequent tumors. We found a strong correlation between the detection of HPV-16 DNA in tumor specimens and seropositivity before diagnosis (P<0.001). Seropositive subjects also had a significantly higher risk of having tumors that contained HPV-16 DNA than of having tumors without the viral DNA (odds ratio, 37.5 vs. 2.1), strongly indicating that the cause of the tumor involves the persistent presence of an HPV infection.
Klussmann et al. ask about risk estimates stratified according to sex. Confounding by sex can be ruled out, since the study design included matching according to sex. Furthermore, the risk estimates stratified according to sex are indeed presented (on page 1128 of the article) and did not differ significantly between men and women.
Finally, Sudbø inquires about the meaning of the term “risk factor” as it is used in our study. A factor that increases the risk of a disease is termed a risk factor.3 It is not dependent on the magnitude of the absolute risk of disease. “Risk factor” does not imply the usefulness of the factor for predicting cancer in any given person, particularly not when absolute risks are low. Knowledge of risk factors is useful for estimating the effects of possible preventive actions, since the risk of a disease is expected to drop to the risk level among unexposed subjects if the risk factor is eliminated — for instance, by prophylactic vaccination against HPV.
3 ReferencesJon Mork, M.D.
National Hospital, N-0027 Oslo, Norway
jon.mork@ioks. uio. no Matti Lehtinen, M.D.
National Public Health Institute, FI 00300 Helsinki, FinlandJoakim Dillner, M.D.
MAS University Hospital, S-20502 Malmö, Sweden1
Frisch M ,Biggar RJ ,Goedert JJ . Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst 2000;92:1500-1510
CrossRef | Web of Science | Medline2
Hemminki K ,Dong C ,Frisch M . Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands. Eur J Cancer Prev 2000;9:433-437
CrossRef | Web of Science | Medline3
Rothman KJ, Greenland S. Modern epidemiology. 2nd ed. Philadelphia: Lippincott-Raven, 1998.
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