ARTICLE
Human papillomavirus in head and neck carcinomas: prevalence and clinicopathological relationship

Papilomavírus humano em carcinomas de cabeça e pescoço: prevalência e relação clinicopatológica

Guilherme Petito 1, Sebastião Marcelino de Oliveira Júnior 2, Anamaria Donato de Castro Petito 3, Vera Aparecida Saddi 4

2015
Vol. 27 - Nº.1-2
Pag.06 – 08

ABSTRACT

Introduction:

The human papillomavirus (HPV), associated with other factors such as smoking and drinking, increases the risk of head and neck carcinomas. The presence of the HPV-16 genome, considered as highly carcinogenic, increases the risk by 50%.

Objectives:

To assess the prevalence and clinicopathological relationship of HPV associated with the head and neck carcinomas.

Methods:

This is a systematic literature review, from a bibliographical search on LILACS and MEDLINE databases.

Results:

Thirteen studies were reviewed, which altogether evaluated 1,216 cases of head and neck carcinomas, where HPV was detected, on average, in 36.45% of the cases. HPV-16 was the most prevalent genotype, present in 22 to 100% of positive cases for HPV. A higher prevalence of male subjects was observed in cases where the HPV genome was detected. A lower average age in HPV-positive cases was described in all the studies. An inverse association between the presence of HPV and habits such as smoking and alcohol consumption has been reported, with HPV seeming to be more prevalent in tumors presented by nonsmokers and nondrinkers.

Conclusion:

Despite being associated with smoking and alcohol consumption in some studies, improved prognosis and lower recurrence were reported in head and neck carcinomas with the presence of the HPV genome and a higher prevalence and growing incidence of these tumors in younger individuals.

RESUMO

Introdução:

O papilomavírus humano (HPV) associado a outros fatores, como tabagismo e etilismo, aumenta os riscos de surgimento de carcinomas de cabeça e pescoço, sendo que a presença do genoma do HPV 16, considerado de alto poder cancerígeno, aumenta esse risco em até 50%.

Objetivos:

Avaliar a prevalência e relação clinicopatológica do HPV associado aos carcinomas de cabeça e pescoço.

Método:

Revisão sistemática da literatura, a partir de um levantamento bibliográfico nos bancos de dados LILACS e MEDLINE.

Resultados:

Foram revisados 13 estudos que, em conjunto, avaliaram 1.216 casos de carcinoma de cabeça e pescoço onde o HPV foi detectado, em média, em 36,45% dos casos. Nos 13 estudos, o HPV 16 foi o genótipo mais prevalente, presente em 22 a 100% dos casos positivos para o HPV. Maior prevalência de indivíduos do sexo masculino nos casos em que o genoma do HPV foi detectado. Foi descrito, em todos os estudos, uma menor média de idade nos casos HPV positivo. Associação inversa entre a presença do HPV e hábitos como tabagismo e etilismo tem sido relatada, sendo que o HPV parece ser mais prevalente nos tumores de pacientes não fumantes e não etilistas.

Conclusão:

Apesar de ter sido associado ao tabagismo e etilismo em alguns estudos, foi relatado melhor prognóstico e menor recorrência em carcinomas de cabeça e pescoço que apresentam o genoma do HPV, assim como maior prevalência e uma crescente incidência desses tumores em indivíduos mais jovens.

Keywords

Papillomaviridae
head and neck neoplasm
epidemiology

Palavras-chave

Papillomaviridae
neoplasias de cabeça e pescoço
epidemiologia

INTRODUCTION

Human papillomavirus (HPV) shows a high prevalence in cervical carcinomas and other genital areas. However, its prevalence and etiological relationship in head and neck carcinomas are still being investigated, and several studies have been carried out in recent years that support this idea1,2,3.

Head and neck carcinomas originate from the aggression caused by chemical, physical, or biological agents that lead to the formation of differentiated cells that can develop into a tumor4. Changes in cell genetics lead to the formation of an abnormal process that culminates in cell proliferation, which, if not diagnosed and treated in time, cause the formation of a tumor process with unfavorable prognosis for the patient5.

Its evolution depends on causal factors beyond the affected site. Separately, factors such as tobacco and alcohol consumption and the presence of high-risk HPV can trigger the carcinogenesis but with a lower speed and aggressiveness than when these factors are associated6.

The prognosis of these tumors is still grim, despite the developments in diagnostic techniques and treatment, because they have low survival rates at 5 years, around 58.3% for oral cavity carcinomas and 52.7% for oropharyngeal carcinomas7,8. HPV vaccination campaigns are measures that can influence the natural history of cancers associated with the virus9.

From a systematic review of literature, this study aims to present articles that investigated the prevalence of samples of HPV in head and neck carcinomas and covering the important aspects about the clinical implications of this relationship.

METHOD

This is a systematic review of the literature, from a bibliographical search in the LILACS and MEDLINE databases. The following keywords were used: human papillomavirus; head and neck carcinoma; and prevalence. For the construction of the prevalence table, complete studies were included, which used the polymerase chain reaction (PCR) as the HPV detection method and associated findings to the clinicopathological factors of carcinomas.

RESULTS AND DISCUSSION

Studies carried out in different geographical regions have investigated the presence of HPV-DNA in head and neck carcinomas (Table 1). The identification of the main HPV genotypes present in these tumors was also performed in order to predict the effects of potential HPV vaccines in head and neck carcinomas.

Detection of HPV-DNA and genotyping of HPV-16 in patients, with head and neck squamous cell carcinomas in different countries, from 2000 to 2013.

Year Authors Country/region n HPV (%) HPV-16 (%)
2000 Gillison et al .10 USA/Baltimore 253 25.0 90.0
2002 Ringström et al .1 USA 89 20.0 100.0
2007 Lim et al .11 Malaysia 20 100.0 30.0
2007 Gonzales et al .12 Argentina 16 43.7 28.6
2008 Simonato et al .13 USA 29 5.0 17.2
2008 Oliveira et al .14 Brazil 87 19.5 22.0
2009 Zhao et al .15 China 52 40.4 63.5
2010 Montaldo et al .16 Italy 68 60.3 51.0
2010 Hong et al .6 Australia 198 42.0 87.0
2011 Snietura et al .17 Poland 66 14.0 100.0
2011 Elango et al .2 Asia 60 50.0 96.0
2012 Huang et al .18 Taiwan 103 30.1 51.6
2013 Quintero et al .8 Colombia 175 23.9 82.0

As described in Table 1, the presence of HPV-DNA in the reviewed studies ranges from 5% in a study conducted in the United States that evaluated 29 tumors13, to 100% in a study that analyzed 20 tumors in Malaysia11. A study in Brazil showed the presence of HPV in 19.5% of the cases evaluated14. In total, the 13 studies described in Table 1 evaluated 1,216 cases of head and neck carcinomas, and HPV was detected, on average, in 36.45% of cases. In the 13 studies shown in Table 1, HPV-16 was the most prevalent genotype present in 22 to 100% of cases positive for HPV detection.

All the studies shown in Table 1 used the PCR to detect the HPV genome in the carcinomas evaluated. The PCR method has a high sensitivity for the detection of viral genome, but different results can be obtained as a result of the different sets of primers used in the reaction19.

Head and neck carcinomas have always revealed smoking and alcohol consumption as the main risk factors. From the studies conducted in the 1980s, HPV has become associated as a risk agent for these carcinomas. However, in the past 15 years, from the numerous antismoking and antialcohol campaigns around the world, many with positive results, the percentage of head and neck carcinomas associated with the virus has increased20. In the studies presented in Table 1, this relationship is clear, especially, by the presence of HPV-16, considered as of high risk, with high carcinogenic power.

The detection method of the virus genome in the samples is of fundamental importance for the survey of more accurate and reliable results. The PCR is considered a method of high sensitivity and more reliability for this type of study21,22. All the studies listed in Table 1 used the PCR as the HPV detection method.

Wecan observe a high difference in the values presented in different studies, ranging from 5 to 100%. Behavioral and social factors influence the prevalence of the virus in carcinomas of one group studied. In regions where smoking and drinking rates are high, as in some European countries or in some regions within a country, this can influence a lower prevalence of HPV. However, the association between HPV and behavioral factors linked to sexual activity, particularly, oral sex, shows a considerable importance in the prevalence of the virus in these carcinomas19.

Given the high consumption of alcohol and tobacco by young people and a greater tendency to promiscuity and a greater number of partners, the incidence of these tumors in young people is increasing, as reported in the studies on head and neck carcinomas related to HPV23.

Studies have shown a better prognosis with greater survival rates among HPV-positive patients when compared with HPV-negative patients. Lower tendency to metastasis and fewer deaths were more common in HPV-positive groups10. In all the studies described in Table 1, there was a higher prevalence of male subjects.

The association of HPV in head and neck carcinomas reveal an important influence on the profile and clinicopathological characteristics of patients14. HPV-positive groups tend to present a lower average age, lower tendency to metastasize, and fewer deaths when compared with HPV-negative groups7,10. All the studies surveyed reported a lower average age in HPV-positive groups. HPV was associated with smoking habits in several studies8,14,16, with no significant values that counteract a higher prevalence of HPV in groups with smoking habits.

CONCLUSION

In the 13 studies analyzed, HPV was detected, on average, in 36.45% of cases, and HPV-16 was the most prevalent genotype, present in 22 to 100% of HPV-positive cases. The highest prevalence of cases was in male subjects, and the same occurred only in cases in whom the HPV genome was detected. Lower average age, in HPV-positive cases, has been reported in all studies. An inverse association between the presence of HPV and habits such as smoking and drinking has been reported (i.e., HPV seems to be more prevalent in tumors in nonsmoking and nondrinking patients). However, HPV was associated with smoking and alcohol consumption in some studies. The best prognosis and lower recurrence are reported for the head and neck carcinomas that reveal the HPV genome and a higher prevalence of tumors in younger individuals.

Conflict of interests

Conflict of interests: The authors report no conflict of interests.

Affiliation

1 Master of Genetics, Pontifícia Universidade Católica de Goiás (PUC-GO), Professor at the Pharmacy Undergraduate Program - Ceres (GO), Brazil.
2 Pharmacy Undergraduate Student, Faculdade FACER - Ceres (GO), Brazil.
3 Professor at the Nursing Undergraduate Course, Unievangélica - Ceres (GO), Brazil.
4 Laboratory of Genetic Diversity, Pontifícia Universidade Católica de Goiás; Laboratory of Oncogenetics and Radiobiology, Associação de Combate ao Câncer em Goiás - Ceres (GO), Brasil.

REFERENCES

1. Ringström E, Paters E, Hasegawa M, Posner M, Liu M, Kelsey KT. Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res. 2002;8(10):3187-92.
2. Elango KJ, Suresh A, Erode EM, Subhadradevi L, Ravindran HK, Iyer SK, et al Role of human papilloma virus in oral tongue squamous cell carcinoma. Asian Pac J Cancer Prev. 2011;12(4):889-96.
3. Saini R, Khim TP, Rahman SA, Ismail M, Tang TH High-risk human papillomavirus in the oral cavity of women with cervical cancer, and their children. Virol J. 2010;7:131.
4. Gravitt PE. The known unknowns of HPV natural history. J Clin Invest. 2011;121(12):4593-9.
5. Taby R, Issa JP. Cancer epigenetics. CA Cancer J Clin. 2010;60(6):376-92.
6. Hong AM, Dobbins TA, Lee CS, Jones D, Harnett GB, Armstrong BK, et al. Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Cancer. 2010;103(10):1510-7.
7. Oliveira LR, Ribeiro-Silva A, Zucoloto S. Perfil da incidência e da sobrevida de pacientes com carcinoma epidermóide oral em uma população brasileira. J Bras Patol Med Lab. 2006;42(5):385-92.
8. Quintero K, Giraldo GA, Uribe ML, Baena A, Lopez C, Alvarez E. Genótipos de vírus de papiloma humano de células escamosas de cabeça e pescoço na Colômbia. Braz J Otorhinolaryngol. 2013;79(3):375-81.
9. Sanches EB. Prevenção do HPV: a utilização da vacina nos serviços de saúde. Saúd Pesq. 2010;3(2):255-61.
10. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, et al Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709-20.
11. Lim KP, Hamid S, Lau SH, Teo SH, Cheong SC. HPV infection and the alterations of the pRB pathway in oral carcinogenesis. Oncol Rep. 2007;17(6):1321-6.
12. González JV, Gutiérrez RA, Keszler A, Colacino MC, Alonio LV, Teyssie AR Human papillomavirus in oral lesions. Medicina (B Aires). 2007;67(4):363-8.
13. Simonato LE, Garcia JF, Sundefeld ML, Mattar NJ, Veronese LA, Miyahara GI. Detection of HPV in mouth floor squamous cell carcinoma and its correlation with clinicopathologic variables, risk factors and survival. J Oral Pathol Med. 2008;37(10):593-8.
14. Oliveira LR, Ribeiro-Silva A, Ramalho LN, Simões AL, Zucoloto S. HPV infection in Brazilian oral squamous cell carcinomapatients and its correlation with clinicopathological outcomes. Mol Med Rep. 2008;1(1):123-9.
15. Zhao D, Xu QG, Chen XM, Fan MW Human papillomavirus as an independent predictor in oral squamous cell cancer. Int J Oral Sci. 2009;1(3):119-25.
16. Montaldo C, Mastinu A, Zorco S, Santini N, Pisano E, Piras V, et al Distribution of human papillomavirus genotypes in sardinian patients with oral squamous cell carcinoma. Open Virol J. 2010;4:163-8.
17. Snietura M, Piglowski W, Jaworska M, Mucha-Malecka A, Wozniak G, Lange D, et al. Impact of HPV infection on the clinical outcome of p-CAIR trial in head and neck cancer. Eur Arch Otorhinolaryngol. 2011;268(5):721-6.
18. Huang SF, Li HF, Liao CT, Wang HM, Chen IH, Chang JT, et al Association of HPV infections with second primary tumors in early-staged oral cavity cancer. Oral Dis. 2012;18(8):809-15.
19. Castro TM, Bussoloti Filho I, Nascimento VX, Xavier SD HPV detection in the oral and genital mucosa of women with positive histopathological exam for genital HPV, by means of the PCR. Braz J Otorhinolaryngol. 2009;75(2):167-71.
20. Muñoz N, Castellsagué X, González AB, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine. 2006;24(Suppl. 3):1-10.
21. Pannone G, Santoro A, Papagerakis S, Lo Muzio L, De Rosa G, Bufo P. The role of human papillomavirus in the pathogenesis of head & neck squamous cell carcinoma: an overview. Infect Agent Cancer. 2011;6:4.
22. Chaiwongkot A, Pientong C, Ekalaksananan T, Kongyingyoes B, Thinkhamrop J, Yuenyao P, et al. Evaluation of primers and PCR performance on HPV DNA screening in normal and low grade abnormal cervical cells. Asian Pac J Cancer Prev. 2007;8(2):279-82.
23. Oliveira MC, Andrade MC, Menezes FS. Epidemiology of HPV in head and neck cancer. In: Broeck DV. Human Papillomavirus and related diseases - from bench to bedside: a clinical perspective. Chapter 9. Croatia: InTech; 2012. p. 197-220.

Address for correspondence:


. Avenida Brasil, s/n, quadra 13 - St. Morada Verde. Ceres (GO), Brasil. CEP: 76300-000. Tel: +55 (62) 3323-1040. E-mail: guilherme.petito@hotmail.com

History

Received: 12/02/2014

Accepted: 03/02/2015

Views: 392