Human papillomavirus (HPV) is now established as the principal cause of an increase in incidence of a subset of head and neck squamous cell cancers (HNCs) in numerous geographic regions around the ...world. Further study of the epidemiology of HPV-positive HNC will be critical to the development and implementation of public health interventions to reverse these global incidence trends. Here, recent data are reviewed to provide insight into several topics, including incidence trends and projections for HPV-positive HNC; the worldwide HPV-attributable fraction; sex disparities in cancer risk; the epidemiology of oral HPV infection; the latency period between infection and cancer; the potential impact of prophylactic HPV vaccination; and prospects for secondary prevention through screening for oral HPV infection or seroreactivity to viral antigens. The identification of a single necessary cause for any cancer provides a rare and perhaps extraordinary opportunity for cancer prevention.
Oral human papillomavirus (HPV) infection is a cause of oropharyngeal cancer. We investigated whether sexual behaviors that elevated the odds of oropharyngeal cancer developing in a case-control ...study similarly elevated the odds of oral HPV infection developing among control patients. HPV infection was detected in 4.8% of 332 control patients from an outpatient clinic and in 2.9% of 210 college-aged men (age range, 18–23 years). Among control patients, the odds of infection developing independently increased with increases in the lifetime number of oral (P=.007, for trend) or vaginal sex partners (P=.003, for trend). Among college-aged men, the odds of oral HPV infection developing increased with increases in the number of recent oral sex partners (P=.046, for trend) or open-mouthed kissing partners (P=.023, for trend) but not vaginal sex partners. Oral sex and open-mouthed kissing are associated with the development of oral HPV infection
Human papillomavirus (HPV) has been identified as the cause of the increasing oropharyngeal cancer (OPC) incidence in some countries. To investigate whether this represents a global phenomenon, we ...evaluated incidence trends for OPCs and oral cavity cancers (OCCs) in 23 countries across four continents.
We used data from the Cancer Incidence in Five Continents database Volumes VI to IX (years 1983 to 2002). Using age-period-cohort modeling, incidence trends for OPCs were compared with those of OCCs and lung cancers to delineate the potential role of HPV vis-à-vis smoking on incidence trends. Analyses were country specific and sex specific.
OPC incidence significantly increased during 1983 to 2002 predominantly in economically developed countries. Among men, OPC incidence significantly increased in the United States, Australia, Canada, Japan, and Slovakia, despite nonsignificant or significantly decreasing incidence of OCCs. In contrast, among women, in all countries with increasing OPC incidence (Denmark, Estonia, France, the Netherlands, Poland, Slovakia, Switzerland, and United Kingdom), there was a concomitant increase in incidence of OCCs. Although increasing OPC incidence among men was accompanied by decreasing lung cancer incidence, increasing incidence among women was generally accompanied by increasing lung cancer incidence. The magnitude of increase in OPC incidence among men was significantly higher at younger ages (< 60 years) than older ages in the United States, Australia, Canada, Slovakia, Denmark, and United Kingdom.
OPC incidence significantly increased during 1983 to 2002 predominantly in developed countries and at younger ages. These results underscore a potential role for HPV infection on increasing OPC incidence, particularly among men.
There is currently sufficient evidence to conclude that human papillomavirus (HPV) plays a role in the pathogenesis of a distinct subset of head and neck squamous cell cancers (HNSCC), particularly ...tonsillar cancers. There is a strong and consistent association between high-risk HPV types, specifically HPV16, a known human carcinogen, and these distinctive oropharyngeal cancers with molecular characteristics indicative of viral oncogene function. Risk for HPV-HNSCC is increased by certain sexual behaviors after consideration of alcohol and tobacco exposure, consistent with an extensive literature that has established HPV infection as a sexually transmitted disease. Furthermore, exposure to HPV16 has been associated with increased risk for subsequent development of oropharyngeal cancer. Prophylactic and therapeutic vaccines targeted against the viral capsid components and oncoproteins will provide the ultimate evidence for a role for HPV in HNSCC, if demonstrated to be effective in the prevention or therapy of this disease. It is time for clinician scientists to translate knowledge of this newly recognized disease entity into potential applications for the prevention, detection, and treatment of HPV-HNSCC.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with an annual incidence of approximately 400,000
worldwide. Although the principal risk factors for head and neck cancer ...remain tobacco and alcohol use, human papillomavirus
(HPV) has recently been found to be etiologically associated with 20 to 25% of HNSCC, mostly in the oropharynx. HPV causes
human cancers by expressing two viral oncoproteins, E6 and E7. These oncoproteins degrade and destabilize two major tumor
suppressor proteins, p53 and pRb, through ubiquitination. Additional studies have shown that E6 and E7 can directly bind to
multiple host proteins other than p53 and pRb (e.g., Bak and p21 Cip1 ), further contributing to genetic instability. However, expression of E6 and E7 alone is not sufficient for cellular transformation,
and the additional genetic alterations necessary for malignant progression in the setting of virus-induced genomic instability
are unknown. In addition to the etiological differences, HPV-positive cancers are clinically distinct when compared with HPV-negative
cancers with regard to treatment response and survival outcome, with tumor HPV-positivity being a favorable prognostic biomarker.
Further understanding of carcinogenesis and clinical behavior of HPV-positive cancers will improve disease prevention, patient
care, and surveillance strategies for HNSCC patients. (Clin Cancer Res 2009;15(22):6758–62)
Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether ...reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven.
In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI).
Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% (
= .04). For IMRT, 2-year PFS was 87.6% (
= .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6%
52.4%;
< .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% (
= .56).
The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.
Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we ...studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC.
E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index.
Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented.
Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.
PDF
