Understanding personal risk of oropharyngeal cancer: risk-groups for oncogenic oral HPV infection and oropharyngeal cancer

Author: G D’Souza, T S McNeel, C Fakhry
Date: October 19, 2017
Source: Academic.oup.com

Abstract

Background

Incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing. There is interest in identifying healthy individuals most at risk for development of oropharyngeal cancer to inform screening strategies.

Patients and methods

All data are from 2009 to 2014, including 13 089 people ages 20–69 in the National Health and Nutrition Examination Survey (NHANES), oropharyngeal cancer cases from the Surveillance, Epidemiology, and End Results (SEER 18) registries (representing ∼28% of the US population), and oropharyngeal cancer mortality from National Center for Health Statistics (NCHS). Primary study outcomes are (i) prevalence of oncogenic HPV DNA in an oral rinse and gargle sample, and (ii) incident oropharyngeal squamous cell cancer.

Results

Oncogenic oral HPV DNA is detected in 3.5% of all adults age 20–69 years; however, the lifetime risk of oropharyngeal cancer is low (37 per 10 000). Among men 50–59 years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection, yet only 0.7% will ‘ever’ develop oropharyngeal cancer in their lifetime. Oncogenic oral HPV prevalence was higher in men than women, and increased with number of lifetime oral sexual partners and tobacco use. Men who currently smoked and had ≥5 lifetime oral sexual partners had ‘elevated risk’ (prevalence = 14.9%). Men with only one of these risk factors (i.e. either smoked and had 2–4 partners or did not smoke and had ≥5 partners) had ‘medium risk’ (7.3%). Regardless of what other risk factors participants had, oncogenic oral HPV prevalence was ‘low’ among those with only ≤1 lifetime oral sexual partner (women = 0.7% and men = 1.7%).

Conclusions

Screening based upon oncogenic oral HPV detection would be challenging. Most groups have low oncogenic oral HPV prevalence. In addition to the large numbers of individuals who would need to be screened to identify prevalent oncogenic oral HPV, the lifetime risk of developing oropharyngeal caner among those with infection remains low.

Introduction

Human papillomavirus (HPV) is the most commonly sexually transmitted infection in the United States. HPV now causes ∼70% of all oropharyngeal squamous cell cancer (OPC) in the United States [1] and the incidence of HPV-related OPC (HPV-OPC) among men has more than doubled over the past 20 years [2]. Indeed, OPC is projected to be more common than cervical cancer in the United States by 2020 [3]. Given the ‘epidemic’ of HPV-OPC, there is interest in identifying specific groups that could benefit from screening, if effective tests were developed.

Sexual behaviors responsible for exposure to oral HPV infection are common (80% of the US population reports ever performing oral sex) [4]. Given the ubiquitous exposure to HPV infection and resulting anxiety [5], there is interest in identifying healthy individuals most at risk for development of OPC. As oncogenic oral HPV infection is the precursor to malignancy, identification of individuals with oncogenic oral HPV infection may point to individuals with premalignant disease. Such risk triage could both inform screening approaches and assist the public in understanding personal risk. This analysis therefore aims to understand how common HPV16, oncogenic HPV and HPV-OPC are in groups of people with different risk factor profiles.

Methods

Study population

This study included 13 089 people ages 20–69 years old who participated in National Health and Nutrition Examination Survey (NHANES) between 2009 and 2014 and had oral HPV DNA testing. Analyses involving number of oral sex partners were limited to ages 20–59, with data for number of oral sex partners, resulting in a sample size of 9425. Incidence and incidence-based mortality data from SEER 18 registries between 2009 and 2014 [6] were used with NCHS mortality data for projections of OPC risk.

HPV measurement

As previously described [7, 8] oral HPV DNA was tested in exfoliated cells collected from an oral rinse and gargle sample using PCR amplification using PGMY 09/11 consensus primers and line blot for the detection of 37 specific HPV types. Oncogenic oral HPV was defined as detection of any of the following 12 types: HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 [9].

Analytic methods

Analyses of NHANES oral HPV data were weighted by Mobile Examination Center (MEC) exam sampling weights, and conducted using SUDAAN software (release 11.0.1, Research Triangle Institute) to account for survey sample design. Projected OPC risk was calculated using DevCan software [10].

To better understand subgroup risk, prevalence of oncogenic HPV and HPV16 were explored stratifying by multiple factors including sex, sexual behavior, age, and current smoking. Groups with similar prevalence were combined to create parsimonious risk stratification of people with similar prevalence.

Results

Oncogenic oral HPV and oral HPV16 infection are rare in the general US population. As expected, prevalence of infection is higher among men than women of every age group (oncogenic HPV; 6.0% versus 1.1%, P < 0.001; Table 1). Prevalence of oncogenic oral HPV is contrasted with risk of OPC in Table 1 by sex and age groups. While oncogenic oral HPV is detected in 3.5% of all adults age 20–69, the lifetime risk of OPC is low (37 per 10 000). For example, among men 50–59 years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection, yet 0.7% will ‘ever’ develop OPC in their lifetime; and risk of developing OPC in the next 10 (0.2%) or 20 (0.4%) years is even lower (Table 1).

Table 1.

Oral HPV prevalence by sex and age, compared with the risk of developing oropharyngeal cancer (OPC) in each group

    Risk spectrum: infection to cancer

 

NHANESa (prevalence)

 

SEERb (OPC risk: cases/100 people) 

 

Sex  Age  Oncogenic Oral HPV (%)  Oral HPV16 (%)  Lifetime (%)  Next 20 years (%)  Next 10 years (%) 
Men
20–29 4.8 1.1 0.7 0.01 <0.01
30–39 4.7 1.5 0.7 0.07 0.01
40–49 6.2 2.3 0.7 0.3 0.06
50–59 8.1 2.1 0.7 0.4 0.2
60–69 6.1 2.4 0.5 0.4 0.3
Total 6.0 1.9 0.7
Women
20–29 1.4 0.3 0.2 <0.01 <0.01
30–39 1.0 0.3 0.2 0.01 <0.01
40–49 0.8 0.1 0.2 0.05 0.01
50–59 1.6 0.5 0.2 0.08 0.03
60–69 0.7 0.1 0.1 0.10 0.05
Total 1.1 0.3 0.2
Men and women All 3.5 1.1 0.4

a- Weighted prevalence accounting for NHANES study design weights to reflect the general US population.

b- Estimates of OPC risk combine data on cancer occurrence from SEER with population data. OPC is shown as risk per 100 people to contrast with HPV prevalence. For reference in interpretation, 0.6% risk represent that 0.6 people out of the 100 (or 6 out of 1000, or 600 out of 100 000) would develop OPC.

While prevalence of oncogenic oral HPV infection is low, the distribution of infections is not representative of the population (supplementary Table S1, available at Annals of Oncologyonline). Indeed 84% of oncogenic oral HPV infections in 20- to 69-year olds were among men. To elucidate why oncogenic oral HPV was more concentrated among certain groups, behavioral characteristics were considered. Performing oral sex and smoking are each strongly associated with detection of oncogenic oral HPV (Table 2) and HPV16 (supplementary Table S2, available at Annals of Oncology online). Oncogenic oral HPV prevalence is low (<2.5%) among both men and women who never performed oral sex. Prevalence of oncogenic oral HPV increased with number of lifetime oral sexual partners, up to 14.4% in men age 20–59 years old with ≥10 lifetime oral sexual partners (Table 2).

 

Table 2.

Oncogenic oral HPV prevalence by participant characteristics and behaviors

    Oncogenic oral HPV prevalencea(%)

 

 
Men  Women  All 
Characteristics (among those 20–69 years old)  No. of people  N = 6420  N = 6669  N = 13 089  P-valueb 
Sex
Women 6669 1.1 1.1 <0.0001
Men 6420 6.0 6.0
Currently smoke
No 10 041 4.5 0.9 2.6 <0.0001
Yes 3044 10.5 2.1 6.7
Age, in years
 20–29 2738 4.8 1.4 3.1 0.13
 30–39 2668 4.7 1.0 2.8
 40–49 2699 6.2 0.8 3.4
 50–59 2494 8.1 1.6 4.8
 60–69 2490 6.1 0.7 3.3
Race/ethnicity
 White non-Hispanic 5135 6.3 1.1 3.7 0.008
 Black non-Hispanic 2931 7.5 1.4 4.2
 Any race Hispanic 3347 4.5 1.3 2.9
 Other 1676 3.7 0.7 2.1
Ever oral sex (or man or woman)
 No 2453 2.3 0.2 1.1 <0.0001
 Yes 9272 6.5 1.4 4.0
Ever oral sex on a woman
 No 6660 3.6 1.0 1.4 <0.0001
 Yes 5095 6.4 3.5 6.2
Ever oral sex on a man
 No 7054 5.8 0.2 4.9 <0.0001
 Yes 4693 10.2 1.4 1.8
Number of partners performed oral sex on in lifetimec
 0 1661 2.4 0.2 1.2 <0.0001
 1 1877 1.2 1.0 1.1
 2–4 3165 4.8 0.7 2.5
 5–9 1363 3.9 2.5 3.3
 10+ 1359 14.4 3.0 11.1

a- Weighted prevalence accounting for NHANES study design weights to reflect the civilian non-institutionalized US population.

b-Wald F test (based on transforming the Wald χ2) for independence of row variable and oral HPV16, not accounting for sex (except where sex is the row variable).

C- Data on number of lifetime oral sex partners was not collected consistently in those 60 and older so is only presented among those 20–59 years old.

 

 

Oncogenic oral HPV prevalence was explored by sex, sexual behavior, and tobacco use to better understand groups that have higher and lower prevalence (Figure 1). Regardless of what other risk factors participants had, oncogenic oral HPV prevalence was low among those with only ≤1 lifetime oral sexual partner (women = 0.7% and men = 1.7%). Oncogenic oral HPV prevalence doubled among women with ≥2 versus 0–1 lifetime oral sexual partners (1.5% versus 0.7%, P = 0.02), but remained low among women with higher number lifetime oral sexual partners (Table 2). Oncogenic oral HPV prevalence was highest among men who currently smoked and had ≥5 lifetime oral sexual partners (14.9%, 95% CI = 11.4–19.1). Men with only one of these risk factors (i.e. either smoked and had two to four partners or did not smoke and had ≥5 partners) had ‘medium risk’, with 7.3% (95% CI = 5.8–9.1) oncogenic oral HPV prevalence (Figure 1). Findings were similar when considering oral HPV16 infection specifically.

 

What is my risk of oral HPV? Prevalence of oral HPV16 and any oncogenic oral HPV infection by risk group. In the ‘very low-risk’ group (among women with 0–1 lifetime oral sexual partners), oncogenic oral HPV was similar among smokers and nonsmokers (1.8% versus 0.5%, P = 0.26). In the ‘low-risk’ group of women, oncogenic oral HPV prevalence was 1.5% among women with two or more lifetime oral sexual partners. In the ‘low-risk’ group of men, oncogenic oral HPV prevalence was 1.7% among men with 0–1 lifetime oral sexual partners and was higher among men who did not smoke and had 2–4 lifetime oral sexual partners (4.1%, P = 0.0042). In the ‘medium risk’ group, oral HPV16 prevalence was 7.1% among men who smoke and had 2–4 partners and 7.4% among men who do not smoke and had 5+ partners (P = 0.87).

 

Discussion

This analysis highlights that the yield of oncologic oral HPV screening would be limited in most groups in the United States. With the increasing incidence of OPC, there is a need to understand how to identify individuals at risk of OPC. Oncogenic oral HPV detection is attractive as it samples the relevant epithelium in a non-invasive method, has relatively low cost and serves as a biomarker for HPV-OPC. However, for screening to succeed, a high prevalence population is needed to limit false positives, and balance the psychologic and physical harms of screening with the benefits.

From this analysis, it is clear that screening based upon oncogenic oral HPV detection would be challenging. Women across all categories have low prevalence of infection and low risk of OPC and therefore benefits of screening are unlikely to outweigh harms in this group. The higher prevalence of oncogenic oral HPV in men than women is thought be due to both a higher per partner risk of acquisition when performing oral sex [11, 12], and decreased clearance among men than women [11, 13]. While there are specific risk groups of men enriched for oncogenic oral HPV, most men have low prevalence of infection. Even among the elevated risk group, the majority of men do not have a prevalent oncogenic oral HPV. In addition to the large numbers of individuals who would need to be screened to identify prevalent oncogenic oral HPV, the lifetime risk of developing OPC among those with infection remains low [11, 14].

These characteristics suggest that other tests will need to be combined or supplant present methods to accurately identify those with the greatest risk of OPC in the population. Serum HPV oncoprotein antibody tests are specific [15], but are even rarer than oral HPV16 infection [16], so may be impractical to use in most groups. An additional challenge for screening is that precursor lesions for HPV-OPC have not been found and the ability to detect lesions early in an ‘elevated-risk’ group is unknown.

With growing appreciation of the relationship between oral sex, infection, and cancer, some individuals have questions about their risk of having oncogenic oral HPV infection. To address concerns about infection among individuals with high number of oral sex partners or others concerned about their cancer risk, the infographic can be used to reassure that oncogenic oral HPV prevalence is low among most groups. This analysis has several imitations. Data on oral HPV infection were cross-sectional, with no information linking HPV and SEER data used for cancer risk. Comparing oncogenic oral HPV prevalence and OPC risk in this way informs potential future screening studies, and personal risk assessment. In summary, this analysis shows that screening based upon oncogenic oral HPV infection will not be useful and presents data to communicate to the layperson the low risk of infection and cancer.

Acknowledgements

The authors acknowledge Maura Gillison who led the testing for oral HPV in NHANES provided in the publicly available dataset. This dataset has provided investigators the opportunity to better understand the epidemiology of oral HPV infection in the United States. We also acknowledge the contributions of the Oral Cancer Foundation.

Funding

National Institute of Dental and Craniofacial Research (NIDCR) (R35 DE026631).

Disclosure

The authors have declared no conflicts of interest.

 

References

1 Saraiya M, Unger ER, Thompson TD et al. US assessment of HPV types in cancers: implications for current and 9-calent HPV vaccines. J Natl Cancer Inst 2015; 107(6): djv086

 

2 Jemel A, Simard EP, Dorell C et al. Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus(HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst 2013; 105(3): 175-201.

 

3 Chaturvedi AK, Engels EA, Pfeiffer RM et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011;29(32): 4294-4301

 

4 D’Souza G, Cullen K, Bowie J et al. Differnece in oral sexual behaviors by gender, age, and race explain observed difference in prevalence or oral human papillomavirus infection. PLoS One 2014; 9(1): e86023

 

5 D’Souza G, Zhang Y, Merritt S et al. Patient experience and anxiety during and after treatment for and HPV-related oropharyngeal cancer. Oral Oncol 2016; 60: 90-95.

 

6 SEER Incidence and Incidence-Based Mortality Date, SEER 18 Regs (Excl Lousiana) 1973-2014; http://seer.cancer.gov/date/ (8 May 2017, date last accessed).

 

7 Gillison ML, Broutain T, Pickard RKL et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA 2012;307(7): 693-703.

 

8 NHANES 2013-2014: Human Papillomavirus (HPV)- Oral Rinse Data Documentation, Codebook, and Frequencies:

https://wwwn.cdc.gov/Nchs/Nhanes/2013-2014/ORHPV_H.htm (2 May 2017, date last accessed).

 

9 IARC. Human Papillomavirus; http://monographs.iarc.fr/ENG/Monographs/vol100B/mono100B-11.pdf (23 May 2017, date last accessed)

 

10 Devcan: Probability of Developing or Dying of Cancer- Surveillance Research Program; https://surveillance.cancer.gov/devcan/ (8 May 2017, date last accessed).

 

11 D’Souza G, Wentz A, Kluz N et al.   Sex differnces in risk factors and natural history of oral human papillomavirus (HPV) infection. J Infect Dis 2016;213(12):1893-1896.

 

12 Chaturvedi AK, Graubard Bl, Broutian T et al. NHANES 2009-2012 findings: association of sexual behaviors with higher prevalence of oral oncogenic human papillomavirus infections in U.S. men. Cancer Res 2015; 75(12): 2468-2477.

 

13 Beachler DC, Sugar EA, Margolick JB et al. Risk Factors acquisition and clearance or oral human papillomavisur infection among HIV-infected and HIV-uninfected adults. Am J Epidemiol 2015; 181(1): 40-53.

 

14 Pierce Campbell CM, Kreimer AR, Lin H-Y et al. Long-term persistence of oral human papillomavirus type 16: the HPV infection in men (HIM) Study. Cancer Pres Res Phila Pa 2015; 8(3): 190-196.

 

15 Holzinger D, Wichmann G, Baboci L et al. Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma. Int J Cancer 2017; 140(12):2748-2757.

 

16 Beachler DC, Waterboer T, Pierce Campbell CM et al. HPV16 E6 seropositivity among cancer-free men with oral, anal or genital HPV16 infection. Papillomavirus res 2016; 2: 141-144.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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October, 2017|Oral Cancer News|

3 Lessons From An Alarming Case Of Mistaken Cancer Gene Test Results And Surgery

Date: October 28, 2017
Source: Forbes.com
Author: Elaine Schattner

A horrifying story broke last week about a 36-year-old Oregon woman who had elective surgery to remove her uterus and breasts. Elisha Cooke-Moore underwent a prophylactic total hysterectomy and bilateral mastectomy, with nipple-sparing reconstruction and implants, after medical practitioners informed her she had cancer-causing genes. Only later, she learned she didn’t have the abnormality about which she’d been informed. There’s a lawsuit.

As reported in The Washington Post, Cooke-Moore expressed concerns to a doctor about her family’s cancer history before getting tested for mutations in BRCA-1, BRCA-2 and related genes in 2015. A nurse practitioner reviewed the results and erroneously told her she had Lynch syndrome because of an MLH1 mutation. BRCA testing was “negative.” It’s not clear if any doctor directly reviewed the lab report. An obstetrician-gynecologist informed Cooke-Moore that her chances of developing breast cancer were 50% and for uterine cancer up to 80%. In 2016, at least two surgeons operated.

Cooke-Moore discovered the mistake while looking over her medical records: The MLH1 result was “negative,” she noted in 2017. “I am damaged for the rest of my life,” Cooke-Moore told The Washington Post.

Never mind the specifics. While it sounds like the plaintiff received egregious care, and I am sympathetic, I see this as a larger story of confusion over genetic test results leading to irreversible harm. My aim here is not to probe Cooke-Moore’s results or the circumstances of her decisions, but to consider the lessons for other patients and doctors. This case should be a wake-up call about the quality of DNA testing and what variable guidance patients receive about their results. The implications are broad.

Checking genes for presence or absence of mutations is not straightforward as you might think. Mutations vary: They’re rarely “positive” or “negative,” end of story. Some doctors may not fully appreciate the nuances of genetic findings. While some DNA abnormalities are clearly linked to disease, such as mutations tied to cystic fibrosis or sickling of hemoglobin, often there’s a range of severity of illness and pathology among affected patients. Among the cancer risk genes, BRCA-1 and -2 are probably the best studied. Yet even for those, doctors don’t yet understand why some people who inherit BRCA mutations don’t develop cancer, i.e., what mitigates disease risk. Some changes are deemed variants of uncertain significance.

Given the enormity of this subject, I’ll focus on three practical measures to reduce regrettable outcomes after testing for cancer genetic risk.

  1. If you consider getting tested for familial cancer risk, ask where your sample will be evaluated, and exactly what genes will be tested.

The practitioner may or may not know the answer to these questions. But part of the point of asking is to ensure that the responsible physician or genetics counselor is clued in to the details because gene testing companies vary in their methods, which gene variants they report, how fully they report on those, and how they interpret any detected abnormalities.

Some companies, like Myriad Genetics, focus on BRCA and related cancer risk-associated genes. Myriad offer various testing panels to assess hereditary cancer risk. Some large and more general commercial laboratories, like LabCorp and Quest Diagnostics, offer BRCA-related panels (BRCAssure and BRCAdvantage, respectively). Ambry is another player in this field. More recently Color Genomics, a San-Francisco based company, entered the fray; they’ll check your BRCA status for less. Some universities and hospitals offer “in house” testing.

These labs (and this is not a comprehensive list) use distinct and sometimes proprietary ways of extracting DNA from samples, amplifying and analyzing genetic material. They employ different scientists who develop methods and interpret results variously in context of the rapidly-growing literature on cancer risk and cancer-related mutations. The doctor who orders genetic tests should be aware of these possible differences.

At the minimum, before making any decisions I’d want to know that my test was performed in a CLIA-certified laboratory.

  1. Before taking any treatment based on a genetic test result, hit the pause button. Get a copy of the full report and keep it. Ask questions. Try to get a second opinion.

Before agreeing to anything so drastic as prophylactic surgery, or taking medication aimed at reducing cancer risk, you might want to have the test repeated, to confirm or supplement initial results. Even nonprescriptive changes, like adjusting your diet, or participating in a clinical trial for people with specific genetic variants, carries possible benefits and risks. You might wind up taking a medicine, or getting screened in a way that you would not have otherwise.

Among the questions I’d want to ask a doctor are these: “How confident are you about the accuracy of my test result?” and “What are the implications for my health?”

Whenever possible, get a second opinion before a major procedure or treatment is implemented. Ideally, advice would come by a physician familiar with both the nitty-gritty of DNA testing and the relevant medical condition. Keep in mind, experts may have informed but distinct and biased perspectives on the significance of an abnormality, such as an MLH1 mutation. The most knowledgeable physicians may not have ready answers when it comes to interpreting DNA findings in context of an individual patient with a unique medical history and concerns. Consulting with a genetics counselor may also be helpful.*

  1. Use the web and other resources, including patient-oriented organizations, to learn what you can about your genetic results.Here’s a partial list of societies and websites that provide information about genetic testing for cancer risk:

Cancer.net offers information about hereditary cancer syndromes that is provided by the American Society of Clinical Oncology;

FORCE (Facing Our Risk of Cancer Empowered) is a patient-oriented organization with many resources and detailed information for people affected by a familial disposition to developing breast, ovarian and other cancers;

The National Cancer Institute’s Genetics of Cancer page includes numerous links to NIH resources for particular cancer risk genes and syndromes;

National Society of Genetic Counselors details the role of genetic counselors and refers to several resources for patients;

The American Society for Human Genetics is a professional organization that offers general information on gene testing and links to additional resources.

I’m constantly amazed at the explosive field of diagnostic human genetic testing. Despite my concerns about the quality and guidance of interpreting results, I’m impressed by the power of diagnostic human genetic testing. For people who are ill, gene testing can be enormously helpful in establishing the cause of disease, pinpointing a diagnosis, and in some situations knowing how best to treat a medical condition. For those who have reason to worry about inheriting a disposition to disease, gene testing could offer life-saving information about pre-emptive or risk-reducing interventions. In each of these circumstances, informed guidance provided by doctors — in interpreting results and in clinical decision-making — is crucial.

 

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October, 2017|Oral Cancer News|

Number of metastatic nodes a predictor for survival in oral cancer

Source: www.onclive.com
Author: Jason Harris

The presence of metastatic lymph nodes was directly correlated with poorer survival in patients with oral cancer. Mortality risk rose continuously with the number of metastatic nodes without plateau, according to findings published in the Journal of Clinical Oncology.

Investigators found that the effect was most pronounced with up to 4 lymph nodes (hazard ratio [HR], 1.34; 95% CI, 1.29-1.39; P < .001). Extranodal extension (HR, 1.41; 95% CI, 1.20-1.65; P <.001) and lower neck involvement (HR, 1.16; 95% CI, 1.06-1.27; P <.001) were also predictors for increased mortality.

Citing the need for more precise staging metrics and treatment stratification, the investigators assessed the effect of quantitative metastatic nodal burden in a large population of patients with oral cavity cancer. Researchers selected oral cavity cancers because of their surgical treatment paradigm with more complete pathologic nodal data.

“Metastatic nodal burden is a central predictor of mortality in patients with oral cavity cancer, with each additional metastatic lymph node conferring escalated risk of mortality,” first author Allen S. Ho, MD, Department of Surgery, Cedars-Sinai Medical Center, and co-investigators wrote. “Classic factors such as lymph node size and contralateral nodal metastasis lack independent prognostic value when accounting for number of metastatic nodes.”

“Our data suggest that deeper integration of quantitative nodal burden could better calibrate the wide spectrum of risk that staging systems presently capture. Such adjustments would be a promising means to more effectively articulate patient prognosis, tailor clinical trial design, and ultimately advance clinical decision making,” added Ho et al.

Investigators at Cedars-Sinai Medical Center in Los Angeles examined data collected in the National Cancer Data Base on adult patients with oral cavity squamous cell carcinoma who underwent upfront surgical resection for curative intent (N = 14,554) from 2004 to 2013. Patients were segregated into node-negative (n = 7906) or node-positive (n = 6648) groups.

Median overall survival was 68.3 months (95% CI, 64.4-71.7), with a median follow-up of 46.5 months (95% CI, 45.7-47.3).

The mean number of lymph nodes examined was 32.1 (standard deviation [SD], ±17.4). Among patients with node-positive disease who had known data, the mean number of identified positive metastatic nodes was 3.3 (SD, ±4.3), 17.2% had lower neck (level 4-5) involvement, 45.2% demonstrated extranodal extension, and 13.3% harbored contralateral nodal involvement.

In univariate analysis, the number of metastatic lymph nodes strongly predicted poorer survival. Estimated 5-year OS was 65.3% for patients with no metastatic lymph nodes compared with 27.5% for patients with 4 metastatic nodes and 9.7% for those with 10 or more. After adjusting for potential confounders in a multivariable model, investigators found that the number of positive metastatic lymph nodes remained closely linked with OS (P <.001).

Investigators noted a change point when 4 metastatic nodes were identified. HR per metastatic lymph node increased steeply up to 4 metastatic LNs (HR, 1.34; 95% CI, 1.29-1.39; P <.001). Beyond that number, each additional metastatic lymph node increased the risk for death more slowly (HR, 1.03; 95% CI, 1.02-1.04; P <.001).

Investigators found an association between an increasing number of lymph nodes examined and improved OS in multivariable analyses (P <.001). A multivariable model with a three-knot restricted cubic spline function showed that, from a baseline of 10 lymph nodes examined, the risk for death declined continuously with each additional node harvested up to a change point at 35 nodes (HR, 0.98; 95% CI, 0.98-0.99; P <.001). There was no significant improvement in survival beyond that change point (HR, 1.00; 95% CI, 0.99-1.00; P = .126).

After adjusting for covariates, including positive metastatic lymph nodes and number of total nodes examined, both extranodal extension (HR, 1.41; 95% CI, 1.20-1.65; P <.001) and lower neck involvement (HR, 1.16; 95% CI, 1.06-1.27; P <.001) were independently associated with mortality risk. Lymph node size and contralateral lymph node involvement (N2c disease) had no significant impact on survival.

Reference:
Ho AS, Kim S, Tighiouart M, et al. Metastatic lymph node burden and survival in oral cavity cancer [published online September 7, 2017]. J Clin Oncol. doi: 10.1200/JCO.2016. 71.1176.

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October, 2017|Oral Cancer News|

Oral sex increases men’s risk of cancer, new study finds

Source: www.deccanchronicle.com
Author: staff

An alarming new study found men who have performed oral sex on five or more partners are at risk of head and neck cancer related to HPV, according to a report by the Daily Mail.

Johns Hopkins researchers warn men may not be aware of this risk, particularly if they smoke. “Among men who did not smoke, cancer-causing oral HPV was rare among everyone who had less than five oral sex partners, although the chances of having oral HPV infection did increase with number of oral sexual partners, and with smoking,” lead author Dr Amber D’Souza, associate professor at the Johns Hopkins Bloomberg School of Public Health told the Daily Mail.

For the study, data was analysed of 13,089 people part of the National Health and Nutrition Examination Survey (NHANES) and tested for oral HPV. That information was compared to data with federal figures on oropharyngeal cancer diagnoses. The results indicated that men had a higher risk of developing the disease compared to women.

The new study’s findings suggest it is crucial for boys to get the HPV vaccine.

While there are 100 different kinds of HPV, only few cause cancer. HPV strains 16 and 18 trigger most cervical cancer. HPV16 also causes oropharyngeal cancer.

Identifying who is at risk is will help curb the disease. “For these reasons, it would be useful to be able to identify healthy people who are most at risk of developing oropharyngeal cancer in order to inform potential screening strategies, if effective screening tests could be developed,” Dr D’Souza told the Daily Mail.

Further research to explore oral HPV infection in young healthy men is currently being conducted.

The study was originally published in the journal Annals of Oncology.

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October, 2017|Oral Cancer News|

7 million American men carry cancer-causing HPV virus

Source: www.nytimes.com
Author: Nicholas Bakalar

The incidence of mouth and throat cancers caused by the human papilloma virus in men has now surpassed the incidence of HPV-related cervical cancers in women, researchers report.

The study, in the Annals of Internal Medicine, found that 11 million men and 3.2 million women in the United States had oral HPV infections. Among them, 7 million men and 1.4 million women had strains that can cause cancers of the throat, tongue and other areas of the head and neck.

The risk of infection was higher for smokers, for people who have had multiple sex partners, and for men who have sex with men. Frequent oral sex also increased the risk. The rate was higher among men who also had genital HPV. (Almost half of men aged 18 to 60 have a genital HPV infection, according to the Centers for Disease Control and Prevention.)

Neither age nor income made a difference in high-risk oral infection rates, but rates among non-Hispanic blacks were higher than other races and ethnicities.

HPV vaccination is recommended starting at age 11 or 12 and is effective, said the senior author, Ashish A. Deshmukh, an assistant professor at the University of Florida, and “it’s crucial that parents vaccinate boys as well as girls.”

The lead author, Kalyani Sonawane, also at the University of Florida, said that behavioral change is important, too, particularly smoking cessation. “The difference in oral HPV infection between smokers and nonsmokers is staggering,” she said.

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October, 2017|Oral Cancer News|

Should women older than 18 get the HPV vaccine?

Source: www.washingtonpost.com
Author: Erin Blakemore

About half of American teenagers have been vaccinated against the human papillomavirus (HPV), the most common sexually transmitted infection in the United States. Should adult women follow suit?

Yes, says Lauri Markowitz, a Centers for Disease Control and Prevention medical epidemiologist who has worked with the advisory committee that makes national vaccination recommendations. “Women 18 to 26 should be vaccinated.”

There’s good reason to follow that recommendation. According to the American Cancer Society, about 12,820 new cases of cervical cancer will be diagnosed in U.S. women this year and more than 4,000 will die of the disease. HPV is thought to be responsible for more than 90 percent of all cervical and anal cancers in men and women. The virus also causes vaginal, vulvar and throat cancers and genital warts.

Although the majority of HPV infections do not cause cancer — most people with an infection never show any symptoms, and infections usually go away on their own — some strains are particularly dangerous. Gardasil 9, the newest HPV vaccine approved by the Food and Drug Administration, protects against nine such strains and, researchers say, may be able to prevent up to 90 percent of cervical cancers. (Older vaccines protect against fewer strains of HPV.)

However, confusion about the way HPV vaccines protect against infection can deter some women. Gardasil 9 is approved for women up to age 26. Like other vaccines, it spurs the body’s immune system to defend itself against a virus. The FDA and CDC say the HPV vaccines are safe and extremely effective: HPV rates in women ages 14 to 19 years fell 64 percent within six years of the vaccine’s introduction in the United States in the mid-2000s and 34 percent in women ages 20 to 24.

The vaccines are most effective if administered before a woman becomes sexually active. The longer a woman has been sexually active and the more partners she has had, the more opportunities she has had to become infected with an HPV strain that overlaps with the vaccine. If she is vaccinated at an older age, the vaccine may be less effective in lowering her cancer risk, Markowitz says. The vaccine can’t clear any HPV that has taken hold; it can only prevent future infection. So essentially if you already have been exposed to one of the strains it protects against, it will be useless against that strain.

That doesn’t mean it’s useless to get vaccinated if you’re older than the recommended age of 11 or 12, Markowitz says. “Your chances of being protected are decreasing, but you will still have some protection,” she says. Although the likelihood that a sexually active woman has been infected with one of the strains the vaccine protects against increases as a woman has more partners, those who didn’t receive the vaccine at the recommended age are still urged to get vaccinated to increase the odds of protection.

Some insurance does not cover the vaccine for those older than 18 — the shots can be costly, though the manufacturer may provide assistance — but it really varies across the board.

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October, 2017|Oral Cancer News|

Complex cancer decisions, no easy answers

Source: blogs.biomedcentral.com
Author: Jeffrey Liu

With the many different options now available for the treatment of cancer, it can be very difficult for both clinicians and patients to decide on the best possible treatment strategy, particularly when faced with a complicated cancer. In this blog, Dr Jeffrey C. Liu reflects on the challenges encountered in cancer decision making, particularly when presented with difficult cases.

When treating cancer, sometimes the treatment decisions are straightforward and unambiguous. For example, surgery is the treatment of choice for an early, uncomplicated tongue cancer. However, many times, the recommendation for cancer treatment is not straightforward and requires combination treatment – one or more of surgery, radiation or chemotherapy.

As a head and neck cancer surgeon, I work with a team to make these treatment decisions, and usually team consensus is achieved. However, when we are faced with the choice of multiple treatments that all have the same chance of cure available, it seems to result in a never ending discussion amongst our team.

Take for example an advanced tonsil cancer. These cancers can sometimes be removed first with surgery, a process which removes both the primary cancer and the lymph nodes in the neck. Then, depending on the pathology results, patients may need radiation treatment, chemoradiation or sometimes no further treatment at all. Meanwhile, chemoradiation alone, and no surgery, is an excellent option. Whether the patient receives surgery or no surgery, the chance of cure is pretty much the same. However, based on the need for additional treatment after surgery, the patient may have better, equivalent, or worse function than chemoradiation alone.

How then can a patient make a decision with imperfect data? I wish I could help my patients better with these complex decisions. Most patients will make this decision only once in their lives. With the increased emphasis on patient autonomy, there is sometimes a feeling to just “present the options and let the patient decide.”

However, when a group of smart experienced doctors who all treat the same cancer, cannot reach an agreement, how is a patient with no experience expected to make the right decision? There is not enough time to explain to patients the observations of hundreds of such decisions and their thousands of outcomes. Some patients are so overwhelmed by the decision, that they just want someone to tell them what to do. Others have so many questions and concerns that they get lost in the details and paralyzed by the process. I don’t know the right answer for such patients.

Unfortunately, there is no option but to choose a treatment strategy and move forward. We all carry the hope that one day, with more research and better understanding, such complex decisions for the treatment of cancer, will become the easy ones.

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October, 2017|Oral Cancer News|

Is alcohol really good for your health? What the research reveals may surprise you

Source: www.consumerreports.org
Author: Julia Calderone

W e’ve long been told that a little wine with dinner may help prevent heart disease and perhaps offer other health benefits.

But some researchers are now questioning whether the perks of moderate drinking—one drink per day for women, two for men—really outweigh potential downsides.

We know that in older adults, too much alcohol can exacerbate high blood pressure, increase the risk of falls and fractures, and lead to strokes, memory loss, and mood disorders. And in this group, alcohol problems, such as the uncontrollable urge to drink, shot up 107 percent between 2001 and 2013, according to a study published in August in JAMA Psychiatry.

Even small amounts of alcohol can interact with medication (see chart here for a list of which ones), and contribute to cancer risk and potentially cognitive decline.

Here’s the latest research and tips on how to ensure that you’re not going overboard:

Benefits and Risks
More than 100 studies have found that a drink or two per day is linked to a 25 to 40 percent reduced risk of heart attack, stroke, and death from cardiac-related problems, according to the Harvard T.H. Chan School of Public Health.

Another study published in August, one that followed more than 333,000 people for 12 years, found that light to moderate drinkers were 21 to 34 percent less likely to die from cardiovascular disease.

But no studies have yet proved directly that alcohol boosts human health. Most research in this area has looked at whether people’s reported drinking behaviors are “associated” with positive or negative health outcomes.

A growing stack of research also suggests that regular, moderate alcohol consumption may have its hazards.

A 30-year study published in June in the British Medical Journal found that men who consumed eight to 12 drinks per week had three times the odds of having an atrophied hippocampus, which is a possible sign of early Alzheimer’s disease. That’s according to the study’s author, Anya Topiwala, Ph.D., a clinical lecturer in the department of psychiatry at the University of Oxford in the U.K.

And other research has found that moderate drinking may be linked to an elevated risk of breast cancer and—especially in smokers—esophageal, mouth, and throat cancers.

Watch Your Intake
Although moderate drinking isn’t without risks, a daily glass of wine is generally fine, says George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism, even if you’re in your 80s or 90s.

“We don’t want to panic people,” Topiwala adds.

But if you don’t drink, she says, there’s no reason to start for your health’s sake. And if you find yourself exceeding the U.S. Dietary Guidelines, Koob says, there’s no controversy: Consider cutting back.

These strategies can help:
Size up your pour. It can be almost impossible to eyeball a standard drink (5 ounces of wine, 12 ounces of beer, or 1½ ounces of distilled spirits). Some wineglasses can hold up to 22 ounces, more than the amount in four drinks. So use a measuring cup or a shot glass to get it right.

Keep tabs. Tracking how many drinks you have per day or week—perhaps with tick marks on a cocktail napkin—can help you stay within your limit.

Alternate with water. Sipping a glass of water or club soda after each alcoholic drink will help you slow down.

Talk to your doctor. If you’re concerned about your drinking, don’t be afraid to bring up the issue at your next checkup.

Note: This article also appeared in the November 2017 issue of Consumer Reports on Health.

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October, 2017|Oral Cancer News|

Penn surgeons become world’s first to test glowing dye for cancerous lymph nodes

Source: www.phillyvoice.com
Author: Michael Tanenbaum, PhillyVoice Staff

Surgeons at the University of Pennsylvania have achieved a global first with the use of a fluorescent dye that identifies cancerous cells in lymph nodes during head and neck cancer procedures.

The study, led by otorhinolaryngologist Jason G. Newman, seeks to test the effectiveness of intraoperative molecular imaging (IMI), a technique that illuminates tumors to provide real-time surgical guidance.

More than 65,000 Americans will be diagnosed with head and neck cancers in 2017, accounting for approximately 4 percent of all cancers in the United States, according to the National Cancer Institute. About 75 percent of these cancers are caused by tobacco and alcohol use, followed by human papillomavirus (HPV) as a growing source for their development.

Common areas affected by these cancers include the mouth, throat, voice box, sinuses and salivary glands, with typical treatments including a combination of surgery, radiation and chemotherapy.

Lymph nodes, which act as filters for the immune system, are often among the first organs affected by head and neck cancers as they spread or resurface. Initial surgeries may leave microscopic cancerous cells undetected in the lymphoid tissue, heightening the risk that a patient’s condition will return after the procedure.

“By using a dye that makes cancerous cells glow, we get real-time information about which lymph nodes are potentially dangerous and which ones we can leave alone,” Newman said. “That not only helps us remove more cancer from our patients during surgery, it also improves our ability to spare healthy tissue.”

With the aid of a fluorescent dye, surgeons are able to key in on suspicious tissue without removing or damaging otherwise healthy areas. Previously adopted for other disease sites in the lungs and brain, the practice now allows Newman’s team to experiment with indocyanine green (ICG), an FDA-approved contrast agent that responds to blood flow.

Newman explained that since tumor cells retain the dye longer than most other tissues, administering the dye prior to surgery singles out the areas where cancer cells are present.

The current trial at Penn will enable researchers to determine whether ICG is the most suitable dye for head and neck cancers and provide oncologists with a deeper understanding of how cancer spreads in the lymph nodes.

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October, 2017|Oral Cancer News|

Lindsey Stirling Honors Her Late Father with Moving Routine on Dancing with the Stars: ‘I Felt Like I Was Dancing with My Dad’

Author: Karen Mizoguchi
Source: People.com
Date: October 9, 2017

Lindsey Stirling has had an incredibly tragic year. The violinist is mourning the loss of her father, Stephen, who died of throat cancer. And on Monday night’s episode of Dancing with the Stars, she honored him with her routine for Most Memorable Year Week, choosing 2017.

“I am the woman I am today because of you and I love you so much,” she said on the reality dancing competition series.

To celebrate her dad’s life, Stirling and pro partner Mark Ballas — who wore her father’s hat and scarf as part of his costume — performed a touching Viennese Waltz. “I felt like I was dancing with my dad,” said Stirling, who was awarded a 26/30 by judges.

“I feel like I got to thank my dad in a way I’ve never been able to before. I was really looking forward to this dance, I was terrified to do it and I’m really happy,” she said. “When you’re dancing about something that is so important that means so much to you doing something I’ve never done before, I just wanted it to be so special. And I feel like it was.”

In January, the YouTube star announced the sad news on Facebook, Twitter and Instagram, writing, “My dad passed away early this morning. There is nothing to say that could express my gratitude for this amazing, selfless man.”

She added, “But I love you daddy. I’m the woman I am today because of you.”

Along with the loving message, the America’s Got Talent alum shared a childhood photo of herself and her father.

In June 2016, Stirling’s father, a religious educator and author, detailed his battle with cancer on his website.

“The pain in my throat persists. (That pain is likely the residual result of radiation and chemotherapy. In other words, I now suffer from the cure, now that the disease has fled.  Ironic.),” he wrote about his illness, which he was diagnosed for in late 2015.

The father of five wrote his final Facebook post. “As I prepare to write the next chapter of my life, I am not afraid. God be with you ’til we meet again,” he said.

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October, 2017|Oral Cancer News|