Human Papillomavirus-Related Diseases: Oropharynx Cancers and Potential Implications for Adolescent HPV Vaccination

doi:10.1016/j.jadohealth.2008.07.002

Journal of Adolescent Health

Volume 43, Issue 4, Supplement, October 2008, Pages S52-S60

https://doi.org/10.1016/j.jadohealth.2008.07.002 Get rights and content

Abstract

Molecular and epidemiological data now support an etiologic role for oncogenic human papillomavirus (HPV) in oral cancers in women and men. Recent studies have demonstrated an increase in the incidence of HPV-associated oral cancers in the United States. Moreover, the incidence rates for these cancers are higher in men than women. Oral HPV infections acquired through oral sex appear to be the principal risk factor for HPV-associated oral cancers. Despite reports in the popular press that the prevalence of oral sexual behaviors is increasing in the adolescent population, trends in these behaviors over time are largely unavailable. However, data indicate that oral–genital contact is frequently practiced among adolescents; adolescents do not typically consider this a risky behavior. The majority of oral cancers (approximately 90%) caused by HPV are identified as HPV 16 positive. Therefore, HPV-associated oral cancers could be prevented by a prophylactic vaccine if the vaccine were demonstrated to be capable of preventing oral HPV 16 infection. These findings have created new potential opportunities for the primary prevention of oral cancers.

Section snippets

Risk Factors for HPV-Associated Oral Cancers

Sexually acquired oral HPV infection appears to be the principal risk factor for HPV-associated oral cancer, a finding of critical importance in potentially preventing HPV-associated oral cancer through vaccination. Case–control studies have consistently demonstrated strong associations between serologic evidence of HPV exposure and risk for head and neck cancers (Table 1). Consistent with the HPV-DNA type distribution reported in molecular studies, risk is strongly and consistently associated

The Potential to Prevent HPV-Associated HNSCC with HPV Vaccines

A detailed discussion on the development of vaccines targeted against oncogenic HPV, as well as the ongoing clinical trials, is available elsewhere in this supplement. All vaccine trials reported to date have been designed to investigate the ability of the vaccines to generate protection against the consequences of anogenital HPV infection in women. However, there is reason to be optimistic that the existing vaccines may be protective against oral HPV infection, and therefore effective in

Oral Sexual Behavior in the US and Implications for Vaccination

Data in support of an association between oral sexual behavior or acquisition of oral HPV infection and risk of oral cancer are sparse. Nevertheless, existing data support a reasonable hypothesis that oral HPV infection, like other viral and nonviral STDs [90], [91], can be acquired via oral sex. Transmission by other means, such as oral-to-oral, remains possible and is an active area of investigation.

The risk of HPV exposure at both oral and anogenital sites may need to be factored into the

Conclusion

It is now apparent that HPV is a causal factor for a distinct group of oral cancers that occur more frequently in men than women. Sexual behavior is associated with risk for this cancer. HPV 16 is found in the majority of HPV-positive oral cancers. The increasing incidence of HPV-associated oral cancer (oropharyngeal cancer) in the US underscores the potential importance of cancer prevention via HPV prophylactic vaccination of both women and men. Currently, vaccines targeted against oncogenic

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Circulating tumor HPV DNA assessments after surgery for human papilloma virus-associated oropharynx carcinoma
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To understand the utility of circulating tumor human papillomavirus DNA (ctHPVDNA) blood testing for HPV-associated oropharynx squamous cell carcinoma (HPV + OPSCC) after definitive surgery.
Prospective cohort study of HPV(+)OPSCC patients with ctHPVDNA test data to assess its accuracy in detecting biopsy-confirmed disease at various post-treatment time points. Eligible patients had p16(+)/HPV(+) OPSCC and ctHPVDNA testing performed at any time pre-operatively and/or postoperatively. In cases of recurrence, patients were excluded from analysis if ctHPVDNA testing was not performed within 6 months of biopsy.
196 all-treatment-type patients had at least one PT ctHPVDNA test. The initial post-treatment (PT) ctHPVDNA sensitivity, specificity, PPV, and NPV were 69.2 % (9/13), 96.7 % (177/183), 60.0 % (9/15), and 97.8 % (177/181). 61 surgery alone (SA) patients underwent 128 PT tests. The initial PT SA ctHPVDNA sensitivity, specificity, PPV, and NPV were 100 % (2/2), 96.0 % (48/50), 50 % (2/4), and 100 % (48/48). 35 of 61 (57.4 %) SA patients had NCCN-based histopathologic indications for adjuvant (chemo)radiation but declined. 3 of 35 (8.57 %) had a positive PT ctHPVDNA test of which 1 of 3 (33 %) had biopsy-proven recurrence. Prospectively, ten patients had a PreT positive ctHPVDNA, underwent SA, refused adjuvant treatment, had an undetectable ctHPVDNA within 2 weeks of SA, and remained free of disease (mean 10.3 months).
The high specificity and NPV of ctHPVDNA after SA suggest ctHPVDNA may have a role in determining the omission of PT adjuvant (chemo)radiation in select patients.
Incidence, trends, and survival of oropharyngeal squamous cell cancer in Aotearoa New Zealand, 2006–2020
2023, Cancer Epidemiology
An increasing trend of oropharyngeal cancer (OPC) has been reported in several countries with different demographic characteristics, and often attributed to increases in human papillomavirus (HPV) infection. The survival of patients with OPC has steadily improved, especially for those with positive HPV status. This study assessed the incidence, trends, and survival of OPC in Aotearoa New Zealand (NZ) by age at diagnosis, sex and ethnicity.
The study included all 2109 patients resident in NZ with a primary diagnosis of oropharyngeal squamous cell carcinoma from 2006 to 2020, identified from the National Cancer Registry. We assessed age-standardised incidence rate (ASR), annual percent change (APC) and overall and relative survival rates.
The average annual incidence of OPC was 2.2 per 100,000 population. There was a steady increase of 4.9% per year over 15 years. Although the incidence rates were higher in males over the study period, the overall rate of increase was similar in males (4.9%) and in females (4.3%). The incidence was highest in the 50–69-year group (8.8/100,000 population). This age group had an incidence that increased by 7.5% per year to 2018, and then declined. The main increase in rates was seen between the birth cohort of 1946–50 and that of 1956–60. The increase in incidence was seen in Māori and Pākehā/European populations, but no increase was seen in Pacific or Asian populations. The 5-year overall relative survival rate improved from 69% in 2006‐13 to 78% in 2014–20. Survival rates were lower in older patients, females, and Māori patients.
This study confirmed a substantial increase in OPC incidence in NZ, with some evidence to suggest a recent slowing in this increase. Māori and Pākehā/European had the highest incidence, while Pacific and Asian populations showed the lowest rates and no increase over the study period. Survival rates have improved over time, but remained lower in some demographic groups.
Metabolic regulation in HPV associated head and neck squamous cell carcinoma
2020, Life Sciences
Citation Excerpt :
Studies show that HPV infection causes about 30–60% of oropharyngeal carcinoma, 12% of pharyngeal cancer and 3% of oral cancer [3]. Oropharyngeal cancer shows the most accepted site for HPV associated tumors after cervical cancer as compared to the other tumor sites of oral cavity (12%) and the oropharynx (14%) (Fig. 1) [19,20]. HPV associated oropharyngeal carcinoma occurs primarily in the tonsils, back of the tongue, or in the palatine region.
Cancer cells exhibit distinct energy metabolic pathways due to multiple oncogenic events. In normoxia condition, the anaerobic glycolysis (Warburg effect) is highly observed in head and neck squamous cell carcinoma (HNSCC). HNSCC is associated with smoking, chewing tobacco, consumption of alcohol or Human Papillomavirus (HPV) infection primarily HPV16. In recent years, the correlation of HPV with HNSCC has significantly expanded. Despite the recent advancement in therapeutic approaches, the rate of HPV infected HNSCC has significantly increased in the last few years, specifically, in lower middle-income countries. The oncoproteins of High-risk Human Papillomavirus (HR-HPV), E6 and E7, alter the metabolic phenotype in HNSCC, which is distinct from non-HPV associated HNSCC. These oncoproteins, modulate the cell cycle and metabolic signalling through interacting with tumor suppressor proteins, p53 and pRb. Since, metabolic alteration represents a major hallmark for tumorigenesis, HPV acts as a source of biomarker linked to cancer progression in HNSCC. The dependency of cancer cells to specific nutrients and alteration of various metabolic associated genes may provide a unique opportunity for pharmacological intervention in HPV infected HNSCC. In this review, we have discussed the molecular mechanism (s) and metabolic regulation in HNSCC depending on the HPV status. We have also discussed the possible potential therapeutic approaches for HPV associated HNSCC through targeting metabolic pathways.
Oral HPV prevalence and HPV vaccination among special needs population in the US
2019, Papillomavirus Research
Special needs population have barriers accessing healthcare, higher incidence of sexual assaults and lower sexual education. Due to the above this study was conducted- 1) To assess the current prevalence of oral HPV infection among individuals with SHCN (special health care needs) as compared to the general population and 2) To compare the prevalence of HPV vaccination in SHCN individuals (within the recommended age groups) to general population.
This data was obtained from NHANES 2013-14 and included 665 individuals with special needs. Weighted prevalence estimates and prevalence ratios (PR) were calculated for oral HPV infection by gender, age (18–59 years), race, smoking history, economic status, and sexual behavior. Prevalence rates were calculated for HPV vaccination.
Oral HPV was detected in 9% (7.1–11.5; p = 0.05) of special needs adults. High-risk HPV genotypes prevalence was also higher among adults with special needs [5.56% (3.9–7.9) vs 3.87% (2.7–5.4)]. The HPV vaccination rates among 9–26 years special needs females (33.5% vs 37%) and males aged 9–21 years (16.7% vs 21.2%) with special needs was lower than non-special needs individuals.
There is higher burden of oral HPV infection among adults with special needs compared to general population. Contrastingly, lower vaccination rates were observed among them within the recommended age groups. Further studies are required to determine the barriers to HPV vaccination among individuals with special needs.
Survival analysis of head and neck cancer: Results from a hospital based cancer registry in southern Karnataka
2019, Clinical Epidemiology and Global Health
Effect of vaccination against oral HPV-16 infection in high school students in the city of Cali, Colombia
2019, Papillomavirus Research
Citation Excerpt :
A study conducted in Sweden with high school students detected HPV in the oral cavity in 3.1% of girls and 0.6% of boys [29]. The HPV detection rates found in the present study are equivalent to those reported by these two studies, and it is important to note that the genotype identified was HPV-16, which is responsible for the development of 50% of cases of cervical cancer in females and identified in almost 90% of cases of oral and oropharyngeal cancers positive for HPV [30]. In the United States, the detection rates of HPV in the oral and oropharyngeal cavity in adolescents were 1.5% in participants 12–15 years old and 3.3% in the 16–20 age group [31].
In recent years, an association between HPV-16 and oropharyngeal cancers has been reported. Therefore, it is necessary to evaluate whether vaccination decreases the exposure of HPV-16 in the oral cavity.
To evaluate the effect of vaccination on oral HPV-16 infection in high school students in the city of Cali, Colombia.
In this cross-sectional study, HPV-16 DNA was detected in samples from the oral cavity and throat of 1,784 high school students of both genders, aged 14–17 years old, in 21 schools in the city of Cali, Colombia. The number in vaccinated girls were 944 vs., 95 unvaccinated girls and 745 unvaccinated boys.
The HPV exposure percentages were: 0.7% in vaccinated girls, 3.2% in unvaccinated girls and 2.3% in unvaccinated boys. The odds ratio (OR) of detection of HPV-16 in vaccinated versus unvaccinated students was 0.28 (95% CI: 0.07–0.88), representing a 72% reduction in HPV-16 detection in students immunized with two doses. The odds of detection of HPV-16 in unvaccinated male students were 3.6 times those of vaccinated girls (OR = 3.6, 95% CI: 1.21–12.81) and increased to almost eight-fold in boys who had initiated sexual activity (OR = 7.74, 95% CI: 1.53–75.09).
HPV vaccination was associated with the reduction of HPV-16 exposure percentages in the oral and oropharyngeal cavity.

View all citing articles on Scopus

: Dr. Gillison has received research funding and has acted as a consultant to Merck Inc. This work was supported by grants from the NIDCR DE016631-02.

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Review articleHuman Papillomavirus-Related Diseases: Oropharynx Cancers and Potential Implications for Adolescent HPV Vaccination

Abstract

Section snippets

Risk Factors for HPV-Associated Oral Cancers

The Potential to Prevent HPV-Associated HNSCC with HPV Vaccines

Oral Sexual Behavior in the US and Implications for Vaccination

Conclusion

Int J Oral Surg

J Invest Dermatol

Oral Oncol

Semin Oncol

Eur J Cancer B Oral Oncol

Oral Oncol

Vaccine

Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

J Clin Virol

Lancet

Pathology

Aust N Z J Public Health

Human papillomavirus and cancers of the upper aerodigestive tract: a review of epidemiological and experimental evidence

Cancer Epidemiol Biomarkers Prev

Detection of human papillomavirus type 16 DNA in carcinomas of the palatine tonsil

J Clin Pathol

Prevalence and expression of human papillomavirus in tonsillar carcinomas, indicating a possible viral etiology

Int J Cancer

Real-time quantitative PCR demonstrates low prevalence of human papillomavirus type 16 in premalignant and malignant lesions of the oral cavity

Clin Cancer Res

Human papillomavirus-positive tonsillar carcinomas: a different tumor entity?

Med Microbiol Immunol (Berl)

Human papillomavirus type 16 is episomal and a high viral load may be correlated to better prognosis in tonsillar cancer

Int J Cancer

A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen

Int J Cancer

A subset of head and neck squamous cell carcinomas exhibits integration of HPV 16/18 DNA and overexpression of p16INK4A and p53 in the absence of mutations in p53 exons 5–8

Int J Cancer

Integrated human papillomavirus type 16 and loss of heterozygosity at 11q22 and 18q21 in an oral carcinoma and its derivative cell line

Cancer Res

Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control

Oncogene

Detection of human papillomavirus DNA and oncoprotein overexpression are associated with distinct morphological patterns of tonsillar squamous cell carcinoma

Am J Pathol

Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas

Int J Cancer

Is the p53 inactivation frequency in squamous cell carcinomas of the head and neck underestimated? Analysis of p53 exons 2–11 and human papillomavirus 16/18 E6 transcripts in 123 unselected tumor specimens

Cancer Res

Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus

J Natl Cancer Inst

Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection

J Natl Cancer Inst

Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control

Cancer Res

Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival

Int J Cancer

Human papillomavirus and p53 mutational status as prognostic factors in head and neck carcinoma

Head Neck

Human papillomavirus type 16 and squamous cell carcinoma of the head and neck

Clin Cancer Res

Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations

Clin Cancer Res

Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: Review and meta-analysis

Int J Cancer

Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial

J Natl Cancer Inst

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

Cancer Epidemiol Biomarkers Prev

Human papillomavirus (HPV) in head and neck cancer

J Clin Virol

HPV infections and tonsillar carcinoma

J Clin Pathol

Clinical implications of human papillomavirus in head and neck cancers

J Clin Oncol

Human papillomavirus seropositivity and risks of head and neck cancer

Int J Cancer

Human papillomavirus 16 and head and neck squamous cell carcinoma

Int J Cancer

Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis

Clin Cancer Res

Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study

J Natl Cancer Inst

Review article
Human Papillomavirus-Related Diseases: Oropharynx Cancers and Potential Implications for Adolescent HPV Vaccination