Posted by: Chris Maloney | June 15, 2013

Was Michael Douglas’ Throat Cancer Caused By HPV?

English: Michael Douglas at the Cannes Film fe...

English: Michael Douglas at the Cannes Film festival (Photo credit: Wikipedia)

US Magazine had a fairly startling claim in its most recent issue. According to their article, actor Michael Douglas may have developed throat cancer after engaging in oral sex. The idea is that the actor was exposed to HPV, or human papillomavirus. So the question is, is that even a possibility?

The short answer is:  maybe.

The longer answer is that HPV seems to be everywhere these days.  That we have a heavily marketed vaccine wouldn’t have anything to do with the sudden interest in HPV and, well, pretty much any cancer?

The systemic review (abstract at the very bottom) says the correlation between HPV and head-and-neck cancers is between 25-35%.  But the abstract directly below puts the estimate at 40-90%.  A U.S. study of saliva gives the number at about 30%.  A Sudanese study put the prevalence at around 4%.

So how does that compare to the general population?  How many of us have HPV orally but don’t have head-and-neck cancer?  A UK study on Laryngeal cancer gave the HPV affected rate at 3% to 40% and the unaffected rate at about 6%.  That’s right, there may be a protective effect of HPV on Laryngeal cancer if you want to play with the numbers enough.

If we aren’t sure about HPV and throat cancer, can we see what it’s effect is on other cancers?  Breast cancer patients, according to a Brazilian study, have a 23% risk of having HPV.  It varies from 13% up to 40% in the U.S., and controls without breast cancer had HPV 13% of the time.  Colon cancer patients had 40% of cancers positive for HPV, while controls had HPV only 6% of the time.

What are we to make of these findings?  Is HPV the cause of throat, breast, and colon cancer as well as cervical cancer?  Is the HPV vaccine the cure for cancer we’ve all been looking for?

Well, when we look at HPV in vaginal cancer, only 53% of patients in those cancers are HPV positive.  If they have HPV, they have a better survival rate and better outcomes than if their cancer is HPV negative.

So the only conclusion that makes any sense is that HPV is involved with many cancers, but may not be a cause.  It may be more an opportunistic infection that shows up when tissue is already undergoing massive changes.  To conclude it is a primary cause of Michael Douglas’ throat cancer is pretty far fetched.

Gynecol Oncol. 2013 May;129(2):406-11. doi: 10.1016/j.ygyno.2013.02.004. Epub 2013 Feb 8.

Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma.

Larsson GL, Helenius G, Andersson S, Sorbe B, Karlsson MG.


Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.



The objectives of this study are to investigate the human papilloma virus (HPV) distribution in vaginal cancer and to evaluate HPV-genotype as well as HPV16-variant impact on prognosis.


Sixty-nine patients diagnosed with primary vaginal carcinoma (1975-2002) were included in the study. Detection of twelve high-risk HPV (hr HPV) and two low-risk HPV (lr HPV) was performed with realtime-PCR. Samples positive for HPV-16 were analyzed for variants in the E6-gene with PCR and pyrosequencing.


53.6% (37/69) of the tumors were found to be HPV-positive, mostly for HPV-16 (N=26). Other HPV-types were HPV-18 (N=2), HPV-31 (N=2), HPV-33 (N=2), HPV-45 (N=1), HPV-52 (N=2), HPV-56 (N=1) and HPV-58 (N=1). Only European subtypes of HPV-16 were represented and the two most common HPV-16-variants were E-p (N=13) and E-G350 (N=11). Patients with HPV-positive tumors (N=37) had a significantly (log-rank test=3.341; p=0.0008) superior 5-year overall survival rate as well as cancer-specific survival rate and progression-free survival rate (p=0.0002; p=0.0004), compared with patients with HPV-negative tumors (N=32). Interestingly, patients with HPV-16-positive tumors had a superior overall survival compared with patients with tumors containing other HPV-genotypes. In a Cox proportional multivariate analysis age, tumor size, and HPV-status were independent and significant prognostic factors with regard to overall survival rate.


HPV-status is of prognostic importance in vaginal carcinoma and varies with viral genotype. In this era of HPV-vaccination, genotypes other than those included in the vaccination program could still lead to vaginal carcinoma with unfavorable prognosis.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID: 23402906

Med Sci (Paris). 2013 Jan;29(1):83-8. doi: 10.1051/medsci/2013291017. Epub 2013 Jan 25.

[Cancers of the upper aerodigestive tract associated with human papillomavirus].

[Article in French]

Badoual C, Péré H, Roussel H, Si Mohamed A, Tartour É.


Service d’anatomie pathologique, hôpital européen Georges Pompidou, 20-40, rue Leblanc, 75015 Paris, France.


Carcinomas of the aerodigestive tract are most often secondary to alcohol and tobacco intoxication. However, it is shown that the oncogenic human papillomavirus (HPV) have an increasing role in the carcinogenesis of these cancers. Patients with HPV+ carcinoma are generally younger and not alcohol and tobacco users. These carcinomas are mainly localized in the oropharynx and in particular at the tonsil. HPV is found in 40 to 90 % of the cancers in the oropharynx, depending on the country. These HPV+ carcinomas have a better prognosis with better radio or chemosensitivity. To date, no change of treatment is recommended, however, several trials are underway. Preventive vaccination of boys is a real public health issue, especially since it is recommended in some countries. Moreover, a better understanding of the tumor microenvironment will ultimately offer therapeutic vaccination.

© 2013 médecine/sciences – Inserm / SRMS.

PMID: 23351698

Otolaryngol Head Neck Surg. 2013 Mar;148(3):436-42. doi: 10.1177/0194599812471938. Epub 2013 Jan 8.

Human papilloma virus prevalence in a multiethnic screening population.

Chen KM, Stephen JK, Ghanem T, Stachler R, Gardner G, Jones L, Schweitzer VP, Hall F, Divine G, Worsham MJ.


Department of Otolaryngology/Head and Neck Research, Henry Ford Hospital, Detroit, Michigan 48202, USA.



The goal was to determine the prevalence of high-risk HPV16 using saliva in a screening population in Detroit, Michigan.


Real-time quantitative polymerase chain reaction was applied to detect HPV16 in saliva DNA from 349 screening subjects without head and neck cancer (HNC), 156 with HNC, and 19 controls. Cut points for human papilloma virus (HPV) positivity were >0 and >0.001 copy/cell. Proportions were compared between groups using exact χ(2) or Fisher exact tests (P < .05).


At a cut point >0, each group had an overall HPV prevalence of more than 5%, with a higher prevalence of 30.8% in the HNC patient group. At a cut point >0.001, the prevalence was lower: 0% in the control, 1.2% in the screening, and 16.7% in the HNC group. In the latter, for both cut points, HPV prevalence was different across sites (<0.001) and significantly higher in the oropharynx than larynx or site as other after Hochberg’s adjustment. At >0, women in the screening group had a higher prevalence of HPV than did men (P = .010), and at >0.001, the prevalence was higher for men in the HNC group than for women (P = .035). In the screening group, at >0, only African Americans had a higher prevalence than Caucasian Americans (P = .025).


In the screening group, a 6.9% and 1.2% screening rate was noted at cut points >0 and >0.001, respectively. The results provide data to inform public health considerations of the feasibility of saliva as a screening tool in at-risk populations with the long-term goal of prophylactic vaccination against oral HPV.

PMID: 23300223

Ecancermedicalscience. 2012;6:282. doi: 10.3332/ecancer.2012.282. Epub 2012 Dec 4.

Frequency and genotype of human papillomavirus among Sudanese patients with head and neck tumours.

Ahmed HG, Mustafa SA, Eltom FM, Babiker AY.


Department of Pathology, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia.



The aim of this study was to determine the frequency and genotype of human papillomavirus (HPV) infections in head and neck squamous cell carcinomas (HNSCCs) and benign head and neck tumours.


A retrospective study was performed on 150 samples of patients diagnosed with HNSCCs and 50 samples obtained from patients diagnosed with benign head and neck tumours. Tumour DNA was amplified using polymerase chain reaction (PCR) with HPV consensus and multiplex primers.


Six of the 150 (4%) HNSCCs were HPV positive. HPV16 was the most prevalent type, with single infections present in 3/6 (50%) cases, whereas HPV18 and HPV33 were detected in 2/6 (33%) and 1/6 (17%), respectively. HPV infections were detected in 3 (50%) cases of oral cavity and 3 (50%) cases of pharynx.


There was a significant association between HPV infection and HNSCCs (P < 0.05). The present data support the importance of HPV infection in oral and larynx tumours.


Sudanese, head and neck cancer, human papillomavirus

PMID: 23226164

J Am Dent Assoc. 2011 Aug;142(8):915-24.

The connection between human papillomavirus and oropharyngeal squamous cell carcinomas in the United States: implications for dentistry.

Cleveland JL, Junger ML, Saraiya M, Markowitz LE, Dunne EF, Epstein JB.


Division of Oral Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, MS F-10, 4770 Buford Highway, Atlanta, Ga. 30341, USA.

Erratum in

J Am Dent Assoc. 2011 Sep;142(9):1005-6.



Results from studies conducted in the past several years suggest that some oropharyngeal cancers, those of the base of the tongue and the tonsils, are associated with high-risk types of human papillomavirus (HPV). In this article, the authors summarize the available evidence regarding the epidemiology of HPV-associated oropharyngeal cancers in the United States, the available HPV vaccines and the implications of these for dentistry. They also examine the differences in HPV prevalence between cancers of the oral cavity and those of the oropharynx.


The authors searched PubMed, Web of Science, The Cochrane Library and the National Guideline Clearinghouse to identify English-language systematic reviews and meta-analyses focused on HPV-associated oropharyngeal squamous cell cancers published from January 2005 through May 2011.


Molecular and epidemiologic evidence suggest a strong etiologic association of HPV with oropharyngeal cancers. The incidence of oropharyngeal cancers in the United States has increased between 1973 and 2007, whereas that of cancers at other head and neck sites has decreased steadily. Compared with HPV-negative cancers, HPV-positive oropharyngeal cancers are associated with certain sexual behaviors, occur more often among white men and people who do not use tobacco or alcohol, and may occur in a population younger by about four years (median ages, 52-56 years). Despite often having a later stage of diagnosis, people with HPV-positive oropharyngeal cancers have a lower risk of dying or recurrence than do those with HPV-negative cancers. The effectiveness of the HPV vaccine in preventing oropharyngeal cancers is unknown.


Dental health care personnel (DHCP) should be knowledgeable about the role of HPV in carcinogenesis, the association of HPV with oropharyngeal cancers and HPV vaccines, and they should be prompt in referring patients with suggestive symptoms for evaluation. DHCP can play an important role in increasing patients’ knowledge about HPV and oropharyngeal cancers.

Copyright © 2011 American Dental Association. All rights reserved.

Comment in

HPV and oral health. [J Am Dent Assoc. 2012]

Oral HPV. [J Am Dent Assoc. 2011]

PMID: 21804058

Int J Gynecol Cancer. 2012 Mar;22(3):343-7. doi: 10.1097/IGC.0b013e31823c712e.

Prevalence of human papillomavirus in breast cancer: a systematic review.

Simões PW, Medeiros LR, Simões Pires PD, Edelweiss MI, Rosa DD, Silva FR, Silva BR, Rosa MI.


Laboratory of Epidemiology and National Institute for Translational Medicine Health Sciences Unit, University of Extremo Sul Catarinense (UNESC), Criciúma, Santa Catarina.



We performed a systematic review and meta-analyses to estimate the prevalence of human papillomavirus (HPV) in breast carcinoma and to explore the reasons for the ongoing controversies about this issue.


A comprehensive search of the Cochrane Library, MEDLINE, CANCERLIT, LILACS, and EMBASE databases was performed for papers published from January 1990 to January 2011. The medical subject heading terms were searched for the following: breast neoplasm, breast lesions, breast cancer, and HPV or human papillomavirus. Statistical analysis was performed using REVMAN 5.0.


Twenty-nine primary studies, including 2211 samples, were analyzed. Overall, HPV prevalence in patients with breast cancer was 23.0% (95% CI, 21.2%-24.8%). The prevalence of HPV ranged from 13.4% (95% CI, 10.2%-16%) in Europe to 42.9% (95% CI, 36.4%-49.4%) in North America and Australia. The prevalence of HPV in controls was 12.9%. Combinations of 9 case-control studies showed that breast cancer was associated with HPV (odds ratio, 5.9; 95% CI, 3.26-10.67).


We found a high prevalence of HPV DNA in breast cancer. There is strong evidence to suggest that HPV has an important role in the development of breast cancer.

PMID: 22214962

Int J Colorectal Dis. 2011 Feb;26(2):135-42. doi: 10.1007/s00384-010-1049-8. Epub 2010 Sep 1.

Human papillomavirus and colorectal cancer: evidences and pitfalls of published literature.

Lorenzon L, Ferri M, Pilozzi E, Torrisi MR, Ziparo V, French D.


II Faculty of Medicine and Surgery, University of Rome La Sapienza, St. Andrea Hospital, Rome, Italy.



The aim of this study is to review published literature regarding a possible role of human papillomavirus (HPV) infection in colorectal cancer in order to understand if HPV infection plays an active role in colorectal carcinogenesis and to highlight evidences and pitfalls of published studies.


We reviewed literature by searching PubMed, Ovid, and the Cochrane databases for published series investigating HPV and colorectal cancer from 1988 to date.


Twenty-one studies investigating a possible correlation between HPV infection and colon cancer have been published. We reviewed 15 case-control studies and six studies investigating a possible role for HPV virus in colorectal carcinogenesis. HPV was detected in the majority of reported series with a significant difference in HPV infection between tumors and disease-free controls or tumor-adjacent tissue; the HPV mean detection rate within carcinomas was 41.7%, comparing to a mean detection rate of 32.8% in adjacent colic mucosae, and 5.8% in disease-free controls (Chi-square test, p = 0.001). The correlation between HPV infection and c-myc amplification, k-ras mutation, and p53 polymorphism or mutations has been investigated; however, the possible role of HPV in colorectal carcinogenesis was not defined.


HPV has been detected in the majority of reported series, but published literature lacks in definitive data regarding standard methods of investigation and stratification of groups and population. These data encourage further studies with the aim to investigate the presence of the virus in larger series, its possible role in oncogenesis, the integration in host genome, the expression of viral oncoproteins, the mutations in HPV positive cancers and routes of colon infection (hematologic/lymphatic spreading or perineal diffusion).

PMID: 20809427

Clin Otolaryngol Allied Sci. 2004 Aug;29(4):301-6.

A systematic review of case-control studies of human papillomavirus infection in laryngeal squamous cell carcinoma.

Rees L, Birchall M, Bailey M, Thomas S.


Laryngeal Research Group, Department of Otolaryngology, Division of Surgery, University of Bristol, Bristol, UK.


A role for human papillomavirus (HPV) has been suggested in laryngeal squamous cell carcinoma (LSCC). In order to quantitate the available evidence, we reviewed studies examining the risk of laryngeal cancer-associated HPV. PubMed was searched for case-control studies conducted worldwide and published in any language since 1966. Relevant papers were hand-searched and cross-referenced. Six studies met the inclusion criteria. The studies are heterogeneous in the methods used to harvest tissue samples and techniques for detecting the virus within the tissue. HPV-16 positivity among cases ranged from 2.7% to 46.9% and 0-5.7% among controls. Two studies showed a significantly increased risk of LSCC if HPV-16 was present (OR 18.5, 95% CI 2.2-154.8, OR 2.6, 95% CI 1.1-6.0). An increased risk was also observed for glottic versus supraglottic cancer in one study (OR 9.69, 95% CI 1.47-64.04). The direction of effect is towards an increase in risk of LSCC in people with evidence of HPV-16 infection. There is marked heterogeneity in the methods used to detect the virus and frequency with which it is detected. An adequately powered study using a reliable detection technique is required to confirm and quantify this risk and to examine effect modification.

PMID: 15270812

Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):467-75.

Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review.

Kreimer AR, Clifford GM, Boyle P, Franceschi S.


International Agency for Research on Cancer, Lyon, France.


Mucosal human papillomaviruses (HPV) are the cause of cervical cancer and likely a subset of head and neck squamous cell carcinomas (HNSCC), yet the global prevalence and type distribution of HPV in HNSCC remains unclear. We systematically reviewed published studies of HNSCC biopsies that employed PCR-based methods to detect and genotype HPV to describe the prevalence and type distribution of HPV by anatomic cancer site. Geographic location and study size were investigated as possible sources of variability. In the 5,046 HNSCC cancer specimens from 60 studies, the overall HPV prevalence was 25.9% [95% confidence interval (95% CI), 24.7-27.2]. HPV prevalence was significantly higher in oropharyngeal SCCs (35.6% of 969; 95% CI, 32.6-38.7) than oral SCCs (23.5% of 2,642; 95% CI, 21.9-25.1) or laryngeal SCCs (24.0% of 1,435; 95% CI, 21.8-26.3). HPV16 accounted for a larger majority of HPV-positive oropharyngeal SCCs (86.7%; 95% CI, 82.6-90.1) compared with HPV-positive oral SCCs (68.2%; 95% CI, 64.4-71.9) and laryngeal SCCs (69.2%; 95% CI, 64.0-74.0). Conversely, HPV18 was rare in HPV-positive oropharyngeal SCCs (2.8%; 95% CI, 1.3-5.3) compared with other head and neck sites [34.1% (95% CI, 30.4-38.0) of oral SCCs and 17.0% (95% CI, 13.0-21.6) of laryngeal SCCs]. Aside from HPV16 and HPV18, other oncogenic HPVs were rarely detected in HNSCC. Tumor site-specific HPV prevalence was higher among studies from North America compared with Europe and Asia. The high HPV16 prevalence and the lack of HPV18 in oropharyngeal compared with other HNSCCs may point to specific virus-tissue interactions. Small sample size and publication bias complicate the assessment of the prevalence of HPV in head and neck sites beyond the oropharynx.

PMID: 15734974

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