Head and Neck Carcinoma in the Young Patient: [Print] eMedicine Otolaryngology and Facial Plastic Surgery
Yüklə 267,24 Kb. Pdf görüntüsü
|
- Bu səhifədəki naviqasiya:
- Head and Neck Carcinoma in the Young Patient Alexander Langerman, MD
- Ibiayi Dagogo-Jack
- Reddening of the soft palate, perhaps with scattered areas of white and velvet red patches, tobacco
- Etiology and Risk Factors Tobacco and alcohol
- Human papillomavirus
|
11/12/10 7:23 AM Head and Neck Carcinoma in the Young Patient: [Print] - eMedicine Otolaryngology and Facial Plastic Surgery Page 1 of 17 http://emedicine.medscape.com/article/855871-print emedicine.medscape.com
eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery Head and Neck Carcinoma in the Young Patient Alexander Langerman, MD, Resident Physician, Department of Otolaryngology-Head and Neck Surgery, University of Chicago Hospitals Elizabeth A Blair, MD, Associate Professor, Department of Surgery, University of Chicago; Ezra Cohen, MD, Assistant Professor, Section of Hematology and Oncology, Associate Director, Head and Neck Cancer Program, University of Chicago; Ibiayi Dagogo-Jack, University of Chicago Pritzker School of Medicine Updated: Apr 21, 2009 Introduction Problem Head and neck squamous cell carcinoma (HNSCC) typically develops in the sixth to seventh decade of life. Since Byers identified this subset of patients in 1975, clinicians have become increasingly aware of patients who develop HNSCC at a young age, variably defined as age 30 years and younger, 40 years and younger, or 50 years and younger. [1 ] These patients may represent a distinct cohort with different risk factors and disease behavior. This article addresses this cohort, defined here as young adults, age 20-45, with HNSCC. As discussed below, these cancers tend to occur in the oral cavity and oropharynx, rather than other head and neck subsites. This article primarily addresses squamous cell carcinoma (SCC), but other histology is noted when appropriate. This article does not address pediatric head and neck tumors, and the reader is referred to other chapters for this topic.
The incidence of HNSCC in young patients is approximately 1-8% of all head and neck cancers, based on modern reports from the United States, Canada, Great Britain, Spain, Scandinavia, India, and Japan. [2,3,4,5,6,7,8,9,10,11 ] Current evidence suggests that this incidence may be increasing. From 1973-2001, Shiboski et al demonstrated an increase of approximately 1-4% in the incidence of oral cavity and pharynx cancer among young whites based on subsite. [4 ] Similarly, Schantz and Yu noted a 60% increase in the incidence of tongue cancer in young patients from 1973-1997, with no increase in incidence for other age groups. [12 ]
Both studies used National Cancer Institute Surveillance, Epidemiology, and 11/12/10 7:23 AM Head and Neck Carcinoma in the Young Patient: [Print] - eMedicine Otolaryngology and Facial Plastic Surgery Page 2 of 17 http://emedicine.medscape.com/article/855871-print End Results (SEER) data for their analyses. The etiology of this increasing trend is unclear, although marijuana use and human papillomavirus (HPV) infection are possible explanations. [4,7,3 ]
Although HNSCC generally remains more common in males, even among young patients, some studies have reported a higher relative incidence in females. [8,13,11,14 ] Furthermore, one report demonstrated a reversal of the typical male-to-female ratio in favor of women within the 35-year-old or younger age group. [10 ]
Additionally, these cohorts of young women lack the typical associated risk factors of alcohol, tobacco, and betel nut exposure and may represent a unique subset even within young HNSCC patients. [10,14,15,1 ]
Funk proposed the following 3 groupings of young patients with head and neck cancer: [14 ] Group I is composed of young women (<35 years) with few to no risk factors and aggressive squamous cell carcinoma (SCC) Group II are typically young males (<40 years) with heavy risk factors and disease typical of older patients Group III has a slight male predominance but fewer risk factors and relatively well-differentiated disease. In Funk’s review of oral cancer in the National Cancer Data Base (NCDB) between 1985 and 1996, the predominant group was Group III. [14
] If this categorization is valid, the group of patients predominating any given study may change the significance of gender and other factors. Race Among the few studies that address race, conflicting data are found in young patients with HNSCC. Shiboski et al found an overall higher percentage of oral cavity and pharynx cancer among young whites compared with young African Americans from a 1973-2001 SEER database analysis and found the incidence of these cancers increased in that time period only among young whites. [4 ] However, Kolker et al, looking at statistics from metropolitan Detroit, a predominantly African American area of Michigan, found a higher incidence of oral and pharyngeal cancer among African Americans compared with whites in the 50 and under age group. [16 ]
Similarly, Slotman et al found a higher incidence of HNSCC in African Americans younger than 45 years in 2 disparate locations. [17 ] The first was in East Orange, Virginia, where 21% of the 847 patients studied from 1968-1980 were African American. The second was the New Jersey Medical School, where 74% of the 219 patients studied from 1970-1980 were African American. Both sites found a trend toward younger age at presentation for African Americans. In the first site, 13% of African Americans presented before age 45, compared with 3% of whites; in the second site, 15.3% of African Americans presented before age 45, compared with 2% of whites. Slotman and colleagues also noted a lower 5-year survival rate for African Americans in all age groups.
No data exist in the above studies to explain the racial differences in age at presentation. Slotman and colleagues suggested that their African American patients may have started using tobacco and alcohol at a younger age, but the authors did not provide comprehensive data to support this theory. [17 ] Clearly, except for the SEER data, the above studies are small and subject to the populations they survey, which may bias their findings.
HNSCC in the young patient tends to occur in the oral cavity and oropharynx. [3 ]
In the oral cavity, the oral tongue is the most common subsite in the young in most series; [8,12,18,14,11 ] the floor of the mouth has been reported as a less common subsite in the young patient compared 11/12/10 7:23 AM Head and Neck Carcinoma in the Young Patient: [Print] - eMedicine Otolaryngology and Facial Plastic Surgery Page 3 of 17 http://emedicine.medscape.com/article/855871-print with older patients. [14 ]
The incidence of oral tongue and tonsil cancer seems to be increasing among younger patients. [19,12,4,20 ] The association of oropharyngeal cancer with HPV infection (see Etiology and Risk Factors) lends circumstantial evidence to that virus’s role in the etiology of HNSCC in the young adult. Because HPV’s role in the etiology of oral cancer is controversial, HPV carcinogenesis is not yet a convincing explanation for the increase in both oral cavity and oropharyngeal tumors.
Within the oral cavity, certain non–SCC histologies also account for a substantial proportion of cancers in the young patient. In particular, adenocarcinoma and Kaposi sarcoma tend to occur on the palate, making the palate another oral cavity subsite that is more common in young patients compared with older patients. [14 ]
[3 ] and nasopharyngeal carcinoma is more common in older adults than in the younger adult. [21 ]
Stage Many of the studies comparing young patients who have HNSCC with old patients with HNSCC use tumor stage as a matching criteria for creating the older, "control" cohort, thus limiting the data comparing stage at presentation. Only those studies looking at whole populations can reliably comment on differences in stage at presentation. Schantz and Yu reviewed the 1973-1997 SEER database and found younger patients to be more likely to present with localized disease than older patients. [12 ]
Similarly, Funk’s review of the 1985-1996 NCDB demonstrated younger patients to present at an earlier stage across all types of histology, and a statistically significant higher proportion of stage I disease among young patients when analyzed only for squamous cell carcinoma (SCC). [14 ]
Contrary to these findings, in small single-institution studies, Verschuur and colleagues and Veness and colleagues both found a higher rate of nodal metastases at presentation in younger patients. [3,22 ] However, Veness and colleagues also found older patients to be more likely to present with a higher T stage compared with younger patients; this latter finding was echoed by Sasaki and colleagues in their single- institution series. [8 ] In summary, although a propensity for increased nodal metastases among some young patients may exist, this has yet to be clearly defined, and evidence from the largest databases suggests young patients present at similar or earlier stages than older patients.
In Byers’s report from 1975, his young patients (<30 years old) with oral tongue squamous cell carcinoma (SCC) had a high percentage (almost 50%) of high-grade histology. [1 ] Four of those patients were female and 7 were male. Since that publication, histology has been addressed specifically by a handful of studies that contradict the assertion that younger patients tend to have more aggressive histology. Atula and colleagues reviewed 34 Finnish patients younger than 40 years with squamous cell carcinoma (SCC) of the tongue and found the vast majority (70%) to have well-differentiated tumors. [23 ]
No older population was reported for comparison. Similarly, Sasaki and colleagues found 66% of young tumors (patients <40 years) to be well-differentiated, compared with only 33% in their older cohort. [8 ]
patients, defined as younger than age 50 years, to make up a higher percentage of high-grade lesions (38%) than low-grade lesions (17%). [24
] This paper scored tumors based on infiltration at the margins, with higher-grade lesions demonstrating infiltrative cords or nests rather than the "pushing" border of lower-grade lesions. In Spiro and colleagues’ series, those patients with higher-grade lesions tended to present with nodal metastases and distant disease but did not have a higher rate of locoregional recurrence compared with lower-grade lesions. Unfortunately, a subset analysis for young patients was not performed for these parameters, so one cannot comment definitively on stage at presentation or recurrence from this paper.
Using Funk’s grouping, Byers’s findings may be explained by involving primarily the unique subset of young patients with aggressive disease (Group I). Spiro’s findings would not fall into that category, and indeed Spiro’s definition of young was considerably older than Byers’ definition. 11/12/10 7:23 AM Head and Neck Carcinoma in the Young Patient: [Print] - eMedicine Otolaryngology and Facial Plastic Surgery Page 4 of 17 http://emedicine.medscape.com/article/855871-print Spiro also had many older patients as well as younger patients with aggressive histology. A bimodal distribution of aggressive histology (the youngest patients and older patients having more aggressive histology) is possible, but this cannot be proven from the available data. Finally, note again that not all oral cavity or head and neck tumors in the young are squamous cell carcinoma (SCC). Funk found a higher percentage of non–SCC histology, particularly adenocarcinoma and Kaposi sarcoma, in patients younger than 35 years compared with their older counterparts. In that series, approximately 48% of oral cavity cancers in patients younger than 35 years were SCC, versus 88% in patients 36-65 years and 91% of patients older than 65 years. [14 ]
In young patients, studies have found a variable and sometimes absent relationship with these traditional risk factors. Several small studies have fallen on both sides of this debate, with some finding a lower rate of tobacco and alcohol use among young head and neck squamous cell carcinoma (HNSCC) patients compared with older HNSCC patients; [25,25,7,11,26 ] however, others found no difference in use. [27,22,28 ] In a review of risk factors in 116 patients from the south east of England, Llewellyn et al found equal and substantial exposure to tobacco and alcohol in young patients with oral SCC and a control group of patients without cancer (both groups were composed of subjects younger than 45 years). [15 ] In their analysis, tobacco consumption for greater than 21 years resulted in a significantly elevated risk of oral cancer. Note that patients starting tobacco use in their teenage years reach the 21-year mark prior to their 40 th birthday. In a smaller, more recent series of 56 patients with oral cavity cancer and controls matched for age, Llewellyn and colleagues found an increased risk of cancer in males who started smoking before their 16 th birthday, reinforcing that tobacco use can still be a risk factor in the young. [18 ]
Similarly, Lipkin and colleagues found a very high rate of heavy alcohol and tobacco use in an analysis of 39 adults with HNSCC age 40 or younger from the Baylor College of Medicine. [29 ] The use of smokeless tobacco has been linked to oral cavity cancer. In an analysis of the SEER database from 1973-1984, Davis and Severson found tongue cancer to increase by 1.8 fold in the 30-39 age group. [19 ]
They juxtaposed their findings to other data that demonstrated an increase in the use of smokeless tobacco among the young. However, as the SEER database did not contain specific data on habits of smokeless tobacco use, the association is conjectural. Interestingly, a third series on young patients with oral squamous cell carcinoma (SCC) by Lewellyn et al highlighted a caveat regarding the connection between tobacco and cancer: an absence of tobacco use doesn’t mean an absence of cancer. They reported that among young patients with cancer, a lack of tobacco use was associated with a delay in seeking medical care for their cancer-related symptoms. [18 ] Thus, young patients with no risk factors (and their physicians) may not suspect cancer despite worrisome signs and symptoms. Clearly, subsets of young patients who present without these risk factors (Funk’s Groups I and III) exist; in fact, 38% of the young women and 18% of the young males in Llewellyn’s larger series had no risk factors. [18 ] Such patients have been the subject of searches for additional etiologies specific to or present in young patients with HNSCC, as addressed below. Marijuana Marijuana use and its association with younger patients has led to suggestions that this may be an unreported risk factor in studies that have found fewer risk factors in younger patients. In the only studies to specifically address marijuana use in young patients, 2 of Llewellyn et al’s series both reported similar use of marijuana among young patients with oral SCC and young controls. [15,5 ] Zhang and colleagues at Memorial Sloan Kettering Cancer Center looked at the incidence of marijuana use among patients with pathologically confirmed squamous cell carcinoma (all head and neck sites) compared with age-matched and sex-matched controls culled from their blood 11/12/10 7:23 AM Head and Neck Carcinoma in the Young Patient: [Print] - eMedicine Otolaryngology and Facial Plastic Surgery Page 5 of 17 http://emedicine.medscape.com/article/855871-print bank records. [30 ]
Most marijuana smokers from both groups were under the age of 55. An increased odds ratio for risk of squamous cell carcinoma among marijuana smokers was found, but, as the authors point out, whether their data was biased by the controls being blood donors (and possibly less likely to be users of illegal drugs) was unclear.
In an age- and sex-matched, case control analysis of HPV-positive and HPV-negative HNSCC at Johns Hopkins, Gillison et al found an association of HPV positivity and marijuana use that increased in strength with increasing cumulative marijuana use. [31 ]
In contrast, the HPV- negative group was more strongly associated with traditional HNSCC risk factors (tobacco, alcohol, and poor oral hygiene). No specific analysis of marijuana use and age with respect to HNSCC in this study was found, but the study does provide further evidence for a subgroup of patients who lack traditional risk factors yet share the risk factors of HPV positivity and marijuana use that many have linked to younger patients. Also, the observed cohorts of younger patients with head and neck cancer that have been reported in previous decades are possibly a result of a wave of generations in which marijuana use had become more commonplace during the teenage years. Diet In 2 of Llewellyn and colleagues’ series, a significant reduction in risk was found in subjects who reported consumption of 3 or more portions of fresh fruit or vegetables per day. [15,5 ]
Generally, a diet high in fruits and vegetables is inversely correlated with a risk of oral cancer, [32 ]
and, based on Lewellyn’s studies, this can also be applied to young patients.
Perhaps the most widely studied virus in the head and neck cancer literature in recent years is HPV, a virus initially linked to cervical carcinogenesis that has now gained interest for its connection to cancer of the oropharynx, particularly the lingual and palatine tonsils. [32 ]
The increasing incidence of tongue and tonsil cancer among young patients has led some authors to suggest that HPV may be responsible for this trend; [4,12 ]
although the connection between oral (versus oropharyngeal) cancer and HPV is controversial. [33,34 ]
In a direct comparison between oral cavity, oropharynx, and larynx squamous cell carcinoma (SCC) samples from young (<50 years) and old (>50 years) patients, Sisk and colleagues found no significant difference by age in the rates of HPV positivity (50% vs 44%, respectively. [35 ]
colleagues did not find an association of HPV positivity with age in 305 patients with HNSCC. [36 ]
Gillison and colleagues, however, in a case control analysis looking at HPV-16 status of 240 patients with HNSCC at Johns Hopkins, found a higher proportion of young patients (<50 years) in the HPV-16–positive group than the HPV-16–negative group (33% vs 17%, respectively). [31
] Additionally, they found a strong association between HPV-16 positivity and oropharyngeal and lingual or palatine tonsil primary sites.
In a multi-institutional, prospective phase II trial of chemoradiation for advanced HNSCC (ECOG 2399) that included analysis of HPV status in the primary biopsy, the mean age of the 38 patients with HPV positive tumors was lower than the 58 with HPV-negative tumors (56 versus 60, respectively), but the difference was not significant. [37 ] However, this study did find a significantly better response and survival in the HPV- positive group, even when adjusted for age, tumor stage, and performance status. Sisk likewise found HPV positivity to be linked to a better overall prognosis, [35 ] and this has been seen in several other studies as well, [32 ] although none of these studies specifically addressed young patients. Interestingly, improved survival was also seen with increasing copy number of HPV-16 in 35 patients with tonsil carcinoma in one study, suggesting that the connection between HPV status and response to treatment may be quite strong. [38 ]
tumors may be one explanation for the markedly different subsets of young patients with head and neck cancer. If tongue cancer, for instance, is not related to HPV, but rather a more sinister, as of yet unidentified risk factor, this would explain the reports by Byers and others that describe young women with aggressive and difficult-to-treat disease (Funk’s Group I).
11/12/10 7:23 AM Head and Neck Carcinoma in the Young Patient: [Print] - eMedicine Otolaryngology and Facial Plastic Surgery Page 6 of 17 http://emedicine.medscape.com/article/855871-print
The Gillison and colleagues’ case control analysis did not address prognosis, but they did find the HPV-16–positive group to be significantly less likely to have the typical risk factors for HNSCC (tobacco, alcohol, poor dental hygiene). [32 ]
Funk’s Group III patients fit into this description. Clearly, more research is needed into the role of HPV in HNSCC and its connection to treatment response, as well as into possible chemopreventive strategies (like those developed for cervical cancer).
Yüklə 267,24 Kb. Dostları ilə paylaş:
|