Human papillomavirus and risk of laryngeal cancer

We determined the relationship between human papillomavirus (HPV) infection and the HPV types detected in 44 patients with squamous cell carcinoma, 10 laryngeal leukoplakia patients, and 12 patients evaluated for benign laryngeal conditions (controls). The sources of HPV DNA were from brushings from the upper respiratory tract and lesion (benign or malignant), oral rinses, and biopsies of patient lesions. Polymerase chain reaction (PCR) and DNA sequencing were used to identify and type HPV. We detected HPV in 25.0% (11/44) of patients with laryngeal cancer, in 30.0% (3/10) of patients with laryngeal leukoplakia, and in 16.7% (2/12) of noncancer controls. Patients with cancer were not more likely to be identified with oncogenic HPV types ( 18.2%) than either the leukoplakia group (20%) or the control group (16.7%). An increased risk of disease was associated with current tobacco use and former alcohol drinking in cancer patients versus controls and in leukoplakia patients versus controls (all p < .05). After we controlled for tobacco and alcohol effects on the risk of disease, exposure to oncogenic HPV types was associated with an increased risk of laryngeal cancer (odds ratio = 3.0) and of laryngeal leukoplakia (odds ratio = 6.0) compared to controls, although the results were not statistically significant. This study suggests that although HPV infection and HPV oncogenic types are not found at a higher frequency in laryngeal cancer or laryngeal leukoplakia as compared to controls, infection is associated with an increased risk of disease after controlling for the effects of alcohol and tobacco use.     

Human papillomavirus infection and oral squamous cell carcinoma - a systematic review

IntroductionThe association between uterine cervix and anogenital carcinomas and human papillomavirus, HPV, is well established, however the involvement of this virus in the development of oral squamous cell carcinomas remains controversial.ObjectivesTo evaluate the relationship between HPV infection and oral squamous cell carcinomas, and to estimate the incidence of this infection in these patients.MethodsFour electronic databases were searched to find studies that met the following inclusion criteria: i) performed in humans; ii) were cohort, case-control or cross-sectional; iii) assessed the HPV oncogenic activity by the E6 and E7 mRNA; iv) included primary oral squamous cell carcinomas which; v) diagnosis had been confirmed by biopsy. Information about the country; study period; sample obtainment; sites of oral squamous cell carcinomas; number, gender and age range of the population; the prevalence of HPV infection and subtypes detected; use of tobacco or alcohol and oral sex practice were extracted. The methodological quality of included articles was assessed using 14 criteria.ResultsThe search strategy retrieved 2129 articles. Assessment of the full text was done for 626 articles, but five were included. The total of participants included was 383, most of them male with mean age between 51.0 and 63.5 years old. Seventeen patients were HPV/mRNA-positive, being the subtypes 16 and 18 detected more frequently. Nine of the HPV/mRNA-positive oral squamous cell carcinomas occurred on the tongue. The quality score average of included articles was five points.ConclusionsAmong the 383 oral squamous cell carcinoma patients included, 17 (4.4%) were HPV/mRNA-positive, nevertheless it was not possible to assess if HPV infection was associated with oral squamous cell carcinomas because none of the studies included was longitudinal and cross-sectional investigations do not have control group.     

Human papillomavirus, smoking, and head and neck cancer

Aims

Smoking and human papillomavirus (HPV) are both distinct risk factors for head and neck cancer, but the nature of interaction between these 2 risk factors in the development of head and neck cancer remains unclear. The purpose of this review is to determine the potential effect of smoking in causation of HPV-related head and neck carcinoma.

Method

A literature search was carried out using the keywords human papillomavirus, head and neck cancer, smoking, tobacco, and cervical cancer. The English-language articles, references, and other relevant studies evaluating the association of smoking, HPV, and risk of head and neck cancer were collected and analyzed.

Conclusion

Overall, our review points to smoking tobacco posing an additional risk for development of head and neck cancer in the presence of HPV infection. This is consistent with available laboratory data that show evidence of biological plausibility for interaction between smoking and progression of HPV infection to carcinogenesis. It is therefore important that cessation of smoking is promoted in smokers with HPV infection.     

Human papillomavirus (HPV) is rarely present in normal oral and nasal mucosa

The association between human papillomavirus (HPV) and cervical carcinomas is well known. HPV has been found in oral carcinomas and paranasal papillomas, and the question of a causal role of HPV has yet to be answered. Reports on the frequency of HPV in oral and paranasal sinus tumours should be considered in relation to the frequency of HPV in normal oral and nasal mucosa. In the present study 61 normal individual had oral smears taken and 48 had nasal smears. These were examined for HPV by DNA amplification with HPV consensus primers. HPV was not found in the oral mucosa, while a single individual harboured HPV in the nasal mucosa. It is concluded that HPV is rarely present in normal oral and nasal mucosa.     

Human papillomavirus in oral squamous cells carcinoma in a population of 75 Brazilian patients

PURPOSE: In the present study, we investigated the presence of human papillomavirus (HPV) DNA and viral types in 75 cases of oral squamous cells carcinoma from Brazil to obtain data that would contribute to a better understanding of the role of HPV in the pathogenesis of this tumor. MATERIALS AND METHODS: DNA was extracted from paraffin-embedded tissue and amplified by polymerase chain reaction using a pair of primers designated PCO3+ and PCO4+ for the detection of a fragment of the human beta-globin gene, followed by polymerase chain reaction for the detection of HPV DNA using a pair of generic primers, GP5+ and GP6+. Viral typing was performed by dot blot hybridization. RESULTS: Human papillomavirus DNA was detected in 18 (24%) of the 75 cases positive for the human beta-globin gene. No significant association was observed between HPV and age, sex, or anatomical location of the tumor. The most prevalent viral type was HPV-18 (77,8%). CONCLUSION: The low frequency of detection of HPV DNA in oral epidermoid carcinomas suggests a possible participation of the virus in the development and progression of only a subgroup of these tumors.     

Human papillomavirus detection in oral rinses and history of tonsillectomy in U.S. adults

PurposeThis study aims to elucidate any relationship between prior tonsillectomy and the presence of oropharyngeal HPV DNA found in screening mouth rinses.Materials and methodsA cross sectional study was conducted using the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Participants between 40 and 69 were included in the study and medical, surgical, and sexual health history were recorded. Multivariable analyses were conducted to examine factors associated with HPV prevalence in oral rinse samples.ResultsA total of 4825 participants were recorded with 21.1 % having a history of tonsillectomy. In the no tonsillectomy group, 8.6 % of respondents had a positive oral rinse for HPV, while 7.2 % of those with a tonsillectomy had a positive rinse sample. There was no association between age and HPV prevalence (OR = 1.04, 95 % CI: [1.00–1.07]). When controlling for demographics, medical history, and sexual behaviors, tonsillectomy history was not shown to have an association with HPV (OR = 0.86, 95 % CI: [0.53–1.40]). However, men, Hispanics, smokers, and those with higher lifetime sexual partners had increased odds of having a positive HPV oral rinse sample which was statistically significant.ConclusionOur data showed that a history of tonsillectomy was not significantly associated with the presence of HPV in an oral rinse. However, a significant relationship was seen between the presence of HPV in oral rinses and certain demographic factors such as male gender, Hispanic race, smoking history, and increased sexual partners.     

Human papillomavirus in larynx

OBJECTIVES: The core of the present clinical and basic research knowledge of laryngeal human papillomavirus (HPV) infection is described. STUDY DESIGN: Review. METHODS: A computer-aided search of MEDLINE database supplemented by hand searches of key journals was conducted. RESULTS: One of the tumor-promoting factors in the larynx is the HPV found both in normal laryngeal epithelium and in laryngeal tumors. The most important manifestation of laryngeal HPV infection is laryngeal papillomatosis, a rare disease caused by HPV types 6 and 11. In laryngeal carcinogenesis, the role of HPV remains uncertain. The means of transmission of HPV are partly unknown, and the course of laryngeal HPV infection is unpredictable and variable. Treatment of laryngeal papillomatosis is based on surgery, especially on CO2 laser and shaver. Alpha-interferon is the drug of choice in patients whose response to surgery is poor. However, neither interferon nor other antiviral drugs are able to eradicate the virus from laryngeal mucosa. Little is known about immunological mechanisms involved in laryngeal HPV infection, but in defense against HPV cellular immunity is considered a more important mechanism than humoral immunity. A good experimental model of HPV infection is lacking in which the entire viral life cycle can take place. Organotypic cell cultures (collagen rafts) are useful, but the rate-limiting step in this method is the difficulties in culturing HPV-positive epithelial cells. CONCLUSIONS: Although laryngeal papillomatosis is clinically well defined, the mechanisms and treatment modalities of laryngeal HPV infection need further investigations.     

Usefulness of human papillomavirus detection in oral rinse as a biomarker of oropharyngeal cancer

Conclusion: The detection of human papillomavirus (HPV)-DNA in oral rinse with auto-nested GP5+/GP6?+?PCR is useful as a biomarker of oropharyngeal cancer.

Background: This study aimed to determine the usefulness of oral rinse to detect HPV-DNA as a biomarker of HPV-positive oropharyngeal cancer (OPC).

Patients and methods: One hundred and ten patients with various head and neck diseases, including 19 patients with OPC, were enrolled. Oral rinse and tonsillar swab were collected, and auto-nested GP5+/GP6?+?PCR for HPV-DNA was performed. For oropharyngeal cancer, p16 immunostaining was also conducted.

Results: The rate of HPV-DNA detection in both oral rinse and tonsillar swab was significantly higher in OPC compared with non-OPC upper respiratory tract cancer and non-cancer diseases. HPV-DNA was detected in oral rinse in nine out of 12 p16-positive OPC cases, while none of the p16-negative OPC cases demonstrated detectable HPV-DNA. All p16-positive cases were also positive for HPV-DNA in tumor tissue. Based on p16 immunostaining, the sensitivity and specificity of HPV-DNA detection in oral rinse were 75% and 100%, respectively. Among eight of nine evaluable OPC cases positive for HPV-DNA in oral rinse at diagnosis, HPV-DNA was undetectable in oral rinse in seven cases after treatment.     

Recurrence in patients with oral and oropharyngeal squamous cell carcinoma: human papillomavirus and other risk factors

CONCLUSIONS: The results confirm that tumour stage influences the risk of recurrence/second primary tumour (SPT). High-risk human papillomavirus (HPV)-infected patients have a significantly higher risk of recurrence/SPT compared with high-risk HPV-negative patients. High alcohol consumption was associated with a higher risk of recurrence/SPT. In this study, the competing risk of death in intercurrent disease (DICD) was given special consideration. OBJECTIVES: The aim of the present study was to evaluate whether any of the factors which were found to increase the risk of oral and oropharyngeal squamous cell carcinoma (OOSCC) in previous analyses (smoking tobacco, alcohol, high-risk HPV infection, oral hygiene, missing teeth and dentures) have an influence on recurrence or the occurrence of a new SPT of OOSCC within the first 3 years following diagnosis. PATIENTS AND METHODS: One hundred and twenty-eight consecutive cases with planned curative treatment, who were part of a population-based case-control study carried out in southern Sweden between September 2000 and January 2004, were included. Only patients for whom the intention was curative treatment were eligible. The cases were followed to the first event of recurrence/SPT, death, loss to follow-up, 30 June 2005 or a maximum of 3 years. Time to the first event of recurrence/SPT was analysed by cumulative incidence, where DICD was a competing risk. Regression was performed on cause-specific hazard rates. RESULTS: After a median follow-up time of 22 months (range 0-36 months), 30 recurrences, 2 SPT, 12 lost to follow-up and 21 deaths before recurrence or SPT were observed. Tumour stage was associated with both a higher risk of recurrence/SPT and of DICD. In univariate analysis, patients with tonsillar carcinoma had a significantly higher risk of recurrence/SPT than patients with carcinoma at other sites, but there was no difference according to site in multivariate analyses. High alcohol consumption was associated with a higher risk of recurrence/SPT, but not of DICD. There was no increased risk of recurrence/SPT related to smoking, but there was an association between smoking and DICD. High-risk HPV-positive cases had a higher risk of recurrence/SPT, but a lower risk of DICD compared with high-risk HPV-negative cases. This seemingly higher risk should be interpreted by taking the competing risk of DICD into account.     

Recurrence in patients with oral and oropharyngeal squamous cell carcinoma: human papillomavirus and other risk factors

Conclusions: The results confirm that tumour stage influences the risk of recurrence/second primary tumour (SPT). High-risk human papillomavirus (HPV)-infected patients have a significantly higher risk of recurrence/SPT compared with high-risk HPV-negative patients. High alcohol consumption was associated with a higher risk of recurrence/SPT. In this study, the competing risk of death in intercurrent disease (DICD) was given special consideration. Objectives: The aim of the present study was to evaluate whether any of the factors which were found to increase the risk of oral and oropharyngeal squamous cell carcinoma (OOSCC) in previous analyses (smoking tobacco, alcohol, high-risk HPV infection, oral hygiene, missing teeth and dentures) have an influence on recurrence or the occurrence of a new SPT of OOSCC within the first 3 years following diagnosis. Patients and methods: One hundred and twenty-eight consecutive cases with planned curative treatment, who were part of a population-based case-control study carried out in southern Sweden between September 2000 and January 2004, were included. Only patients for whom the intention was curative treatment were eligible. The cases were followed to the first event of recurrence/SPT, death, loss to follow-up, 30 June 2005 or a maximum of 3 years. Time to the first event of recurrence/SPT was analysed by cumulative incidence, where DICD was a competing risk. Regression was performed on cause-specific hazard rates. Results: After a median follow-up time of 22 months (range 0–36 months), 30 recurrences, 2 SPT, 12 lost to follow-up and 21 deaths before recurrence or SPT were observed. Tumour stage was associated with both a higher risk of recurrence/SPT and of DICD. In univariate analysis, patients with tonsillar carcinoma had a significantly higher risk of recurrence/SPT than patients with carcinoma at other sites, but there was no difference according to site in multivariate analyses. High alcohol consumption was associated with a higher risk of recurrence/SPT, but not of DICD. There was no increased risk of recurrence/SPT related to smoking, but there was an association between smoking and DICD. High-risk HPV-positive cases had a higher risk of recurrence/SPT, but a lower risk of DICD compared with high-risk HPV-negative cases. This seemingly higher risk should be interpreted by taking the competing risk of DICD into account.     

Human papillomavirus and head and neck cancer: a systematic review and meta‐analysis

?It has been suggested that the link between human papillomavirus (HPV) and head and neck squamous cell carcinoma (HNSCC) is specific to carcinoma of the tonsil. ? We systematically reviewed studies that tested for HPV16 exposure in anatomically defined sites in the head and neck and a control group. ? The association between HPV16 and cancer was strongest for tonsil (OR: 15.1, 95% CI: 6.8–33.7), intermediate for oropharynx (OR: 4.3, 95% CI: 2.1–8.9) and weakest for oral (OR: 2.0, 95% CI: 1.2–3.4) and larynx (OR: 2.0, 95% CI: 1.0–4.2). ? To investigate heterogeneity, further stratification by method of HPV16 detection, suggested that variation in the magnitude of the HPV‐cancer association with cancer site was restricted to studies using ELISA: among studies using PCR, the magnitude of the summary odds ratios was similar across the four sites. ? The association between HPV16 infection and HNSCC in specific sites suggests the strongest and most consistent association is with tonsil cancer, and the magnitude of this association is consistent with an infectious aetiology. ? However, the method of viral detection may be an important source of heterogeneity. Resolution of this issue will require further studies using both methods, examining associations separately in different sites.     

Human papillomavirus co-infection and survival in oral and oropharyngeal squamous cell carcinoma: A study in 235 Brazilian patients

ObjectivesWhile unknown for oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC), some studies assessing cervical carcinoma have shown that human papillomavirus (HPV) co-infection can be associated with its prognosis.MethodsThrough in situ hybridization (HPV and Epstein-Barr virus [EBV] probes) and immunohistochemistry (p16^INK4a, cyclin D1, p53, and Ki-67 antibodies), 126 OPSCC and 109 OSCC samples were assessed.ResultsAll patients were EBV-negative. OPSCC (25%) showed a significant association with HPV compared to OSCC (11%). Almost all HPV-associated cases were p16^INK4a-positive. Regarding OPSCC and OSCC, 23 and 7 cases were positive for high-risk HPV (HRHPV) only, 6 and 3 cases for low-risk HPV (LRHPV) only, and 3 and 2 cases for HRHPV/LRHPV, respectively. HPV-associated carcinomas showed a significantly higher proliferative index than HPV-unassociated carcinomas. Both carcinomas showed a similar overall survival rate, which was not affected by the HPV status. However, when comparing HPV-associated subgroups, patients with HRHPV/LRHPV-associated carcinomas showed worse survival.ConclusionLRHPV-associated and HRHPV/LRHPV-associated cases can also be detected when assessing OSCC and OPSCC. Further studies, especially in populations with a high prevalence of HPV-associated OPSCC, are necessary to understand the clinicopathological behavior of these neoplasm subgroups.