Human papillomavirus (HPV) 16 and the prognosis of head and neck cancer in a geographical region with a low prevalence of HPV infection

Background

The role of human papillomavirus (HPV) on head and neck squamous cell carcinoma (HNSCC) survival in regions with low HPV prevalence is not yet clear. We evaluated the HPV16 infection on survival of HNSCC Brazilian patient series.

Methods

This cohort comprised 1,093 HNSCC cases recruited from 1998 to 2008 in four Brazilian cities and followed up until June 2009. HPV16 antibodies were analyzed by multiplex Luminex assay. In a subset of 398 fresh frozen or paraffin blocks of HNSCC specimens, we analyzed for HPV16 DNA by L1 generic primer polymerase chain reaction. HNSCC survival according to HPV16 antibodies was evaluated through Kaplan–Meier method and Cox regression.

Results

Prevalence of HPV16 E6 and E6/E7 antibodies was higher in oropharyngeal cancer than in other head and neck tumor sites. HPV16 DNA positive in tumor tissue was also higher in the oropharynx. Seropositivity for HPV16 E6 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer. The presence of HPV16 E6/E7 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer survival. The death risk of oropharyngeal squamous cell carcinoma patients HPV16 E6/E7 antibodies positive was 78 % lower than to those who test negative.

Conclusion

Oropharyngeal squamous cell carcinoma is less aggressive in the HPV16 E6/E7 positive serology patients. HPV16 E6/E7 antibody is a clinically sensible surrogate prognostic marker of oropharyngeal squamous cell carcinoma.     

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

BackgroundIncidence 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 methodsAll 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.ResultsOncogenic 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%).ConclusionsScreening 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.     

Association of antibody to E2 protein of human papillomavirus and p16<Superscript>INK4A</Superscript> with progression of HPV-infected cervical lesions

Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16^INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16^INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16^INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16^INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16^INK4A was associated with HPV infection (odds?=?5.444, 95% CI 1.203–24.629, P?=?0.028) and precancerous cervical lesions (odds?=?5.132, 95% CI 1.604–16.415, P?=?0.006). Interestingly, the concurrent detection of anti-E2 and -p16^INK4A antibodies was significantly associated with HPV infection (odds?=?1.382, 95% CI 1.228–1.555, P?=?0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer.     

High‐risk HPV types and head and neck cancer

Although HPV16 has been strongly implicated in oropharyngeal carcinogenesis, the role of other high‐risk HPV types in the etiology of head and neck cancer remains unclear. To date, few data exist addressing the nature of the association between antibodies to oncogenic proteins of non‐HPV16 HPVs in relation to head and neck cancer. We examined the relationship between multiple HPV types (HPV6, 11, 16, 18, 31, 33, 45, 52, 58) and head and neck squamous cell carcinoma (HNSCC) in a large population‐based case–control study (1069 cases and 1107 controls). Serological measures for HPV types included antibodies to L1, E6 and/or E7. In a secondary analysis, we excluded HPV16 seropositive subjects to examine independent associations with other high‐risk HPVs. All analyses were adjusted for age, race, sex, education, smoking and alcohol consumption. Statistically significant associations were observed for HPV16, 18, 33 and 52 and risk of HNSCC after mutually adjusting for HPV types. Among HPV16 seronegative subjects, elevated risks of HNSCC were observed for HPV18 E6 (OR = 4.19, 95% CI = 1.26–14.0), HPV33 E6 (OR = 7.96, 95% CI = 1.56–40.5) and HPV52 E7 (OR = 3.40, 95% CI = 1.16–9.99). When examined by tumor type, associations with HPV18 and HPV33 remained statistically significant for oropharyngeal cancer, and HPV52 was associated with oral cancer. In addition, magnitude of associations for HNSCC increased markedly with increasing number of seropositive high‐risk HPV infections. High‐risk HPV types, other than HPV16, are likely to be involved in the etiology of HNSCC.     

Interrater agreement of anal cytology

BACKGROUND:

The majority of anal cancers are caused by persistent infections with carcinogenic human papillomaviruses (HPV). Similar to cervical carcinogenesis, the progression from HPV infection to anal cancer occurs through precancerous lesions that can be treated to prevent invasion. In analogy to cervical cytology, anal cytology has been proposed as a screening tool for anal cancer precursors in high‐risk populations.

METHODS:

The authors analyzed the interobserver reproducibility of anal cytology in a population of 363 human immunodeficiency virus (HIV)‐infected men who have sex with men (MSM). Liquid‐based cytology (LBC) specimens were collected in the anal dysplasia clinic before the performance of high‐resolution anoscopy on all patients. Papanicolaou‐stained LBC slides were evaluated by 2 cytopathologists, each of whom was blinded to the clinical outcome and the other pathologist's results, using the revised Bethesda terminology.

RESULTS:

Overall agreement between the 2 observers was 66% (kappa, 0.54; linear‐weighted kappa, 0.69). Using dichotomizing cytology results (atypical squamous cells of undetermined significance [ASC‐US] or worse vs less than ASC‐US), the agreement increased to 86% (kappa, 0.69). An increasing likelihood of testing positive for markers associated with HPV‐related transformation, p16/Ki‐67, and HPV oncogene messenger RNA was observed, with increasing severity of cytology results noted both for individual cytologists and for consensus cytology interpretation (P value for trend [p_trend] < .0001 for all).

CONCLUSIONS:

Moderate to good agreement was observed between 2 cytopathologists evaluating anal cytology samples collected from HIV‐positive MSM. A higher severity of anal cytology was associated with biomarkers of anal precancerous lesions. Anal cytology may be used for anal cancer screening in high‐risk populations, and biomarkers of HPV‐related transformation can serve as quality control for anal cytology. Cancer (Cancer Cytopathol) 2013. Published 2012 by the American Cancer Society.     

Antibodies against HPV16E6 oncoprotein in the Swiss HIV cohort study: Kinetics and anal cancer risk prediction

Our aim was to describe HPV16E6 antibody kinetics prior to anal cancer in people living with HIV/AIDS (PLWHA) and evaluate the possible contribution of HPV16E6 serology to anal cancer risk prediction. For 91 persons diagnosed with anal cancer in the Swiss HIV Cohort Study (1989–2017), serial serum/plasma samples were tested for HPV16E6 antibodies using multiplex serology, supplemented with samples from 1,356 participants without anal cancer. Anal cancer incidence was estimated for PLWHA from 40 years-old in the cART era, stratified by HPV16E6 serostatus. HPV16E6 seroprevalence was 23.3% in samples <2 years prior to anal cancer diagnosis and decreased with increasing time prior to cancer: 16.7% at 2–4 years, 4.4% at 5–9, and 7.0% at ≥10 years. Of 25 individuals with anal cancer who were HPV16E6-seropositive at any time during follow-up, the majority (n = 18) remained seropositive in all samples after seroconversion, whereas for seven cases, seropositivity was transitory. Among individuals with anal cancer, HPV16E6 seroprevalence was marginally higher in women vs. men who have sex with men (adjusted OR = 4.3, 95% CI: 1.1, 17.2) and in older participants (adjusted OR = 6.2, 95% CI: 1.1, 34.8 for cases diagnosed at ≥55 vs. <45 years). Anal cancer incidence was 402/100,000 person-years in HPV16E6-positive vs. 82/100,000 in HPV16E6-negative PLWHA (incidence rate ratio = 4.9, 95% CI: 1.3, 13.1). In conclusion, HPV16E6 serology, despite its low sensitivity, allows characterization of a group of individuals with very high anal cancer incidence and may have a place in secondary prevention in groups at high risk for anal cancer such as PLWHA.     

A higher degree of methylation of the HPV 16 E6 gene is associated with a lower likelihood of being diagnosed with cervical intraepithelial neoplasia

BACKGROUND:

Although HPV 16 is the most common HPV genotype associated with cancerous lesions of the cervix, only a fraction of HPV 16 infected women are diagnosed with precancerous lesions of the cervix. Therefore, molecular changes in HPV 16, rather than infections per se, may serve as better screening or diagnostic biomarkers. The purpose of the study was to evaluate whether methylation status of specific regions of the HPV E6 gene promoter and enhancer is independently associated with the likelihood of being diagnosed with higher grades of cervical intraepithelial neoplasia (CIN 2+).

METHODS:

The study included 75 HPV 16‐positive women diagnosed with CIN 2+ or ≤CIN 1. Pyrosequencing technology was applied to quantify methylation at 6 cytosine guanine dinucleotide (CpG) sites of the HPV 16 E6 promoter and enhancer. CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified the degree of methylation of the CpG sites of the HPV 16 E6 gene as the primary independent predictors. All models were adjusted for demographic, lifestyle, known risk factors for cervical cancer, and circulating concentrations of “cancer‐protective” micronutrients.

RESULTS:

The odds of being diagnosed with CIN 2+ were 79% lower when the degree of methylation of the HPV 16 enhancer and promoter sites was ≥9.5% (OR = 0.21; 95% CI, 0.06‐0.79; P = .02).

CONCLUSIONS:

Results suggested that CpG methylation is independently involved in the biology of HPV 16 as well as in the development of higher grades of CIN. Cancer 2011. © 2010 American Cancer Society.     

Human papillomavirus type 16 E6 gene variations in Chinese population

Objective

To identify genetic variants in the E6 gene of HPV 16 and to examine the association between these variants and cervical cancer development.

Methods

Cervical samples were collected from 72 patients with cervical cancer and 72 age-matched control subjects, all from Hubei Province, China. HPV 16 sequence was detected with E6 gene-specific polymerase chain reaction, and variants were identified by DNA sequencing.

Results

HPV 16 was detected in 81% of the patients and 43% of control subjects, respectively. The rank orders of incidence of HPV 16 prototype and E6 variants were as follows: D25E (62%), the prototype (17%), E113D (9%), L83V (6%) in case subjects; the prototype (71%), D25E (23%), L83V/E113D (7%) in control subjects. The odds ratio of HPV 16 E6 variant was higher than that of prototype (RR = 11.73, 95% CI = 4.18–32.94, P = 0.0001).

Conclusion

The D25 E variant is the most prevalent E6 genomic variant in Hubei, China. The presence of HPV 16 E6 variant in cervical intraepithelial neoplasia (CIN) lesions may serve as a useful predictor of clinical outcome of the disease.     

Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers

There are few well-established patient risk factors associated with human papillomavirus (HPV) infection in cancers of the oral cavity and oropharynx. The purpose of this study was to determine if there were significant different risk factors and tumor characteristics between HPV-positive and HPV-negative cancer cases. HPV was evaluated in cancer tissue and exfoliated oral cells of 193 oral cavity/oropharynx cancer patients using PCR and direct DNA sequencing. A patient questionnaire collected information about risk factors, sexual practices and medical history. The prevalence of HPV high-risk (HR) types was 20% in cancer cases. Three types were identified: HPV-16 (87%), HPV-18 (3%) and HPV-33 (11%). Risk factors for HPV-HR included younger age (< or = 55 years vs. > 55 years; adjusted OR = 3.4; 95% CI = 1.6-7.3) and younger-age cases who had more lifetime sex partners (adjusted OR = 3.8; 95% CI = 1.4-10.1), practiced oral-genital sex (adjusted OR = 4.3; 95% CI = 1.8-10.4) or oral-anal sex (adjusted OR = 19.5; 95% CI = 3.4-113). Compared to HPV-negative cancers, HPV-HR cancers were more likely to have a positive HPV-HR exfoliated oral cytology test (adjusted OR = 7.8; 95% CI = 3.4-18.4), later stage (adjusted OR = 3.0), nodal involvement (adjusted OR = 4.1) and advanced grade (adjusted OR = 3.0). This study shows new evidence that the prevalence of oncogenic mucosal HPV is higher in younger-age oral cavity/oropharynx cancer cases whose sexual practices are typically associated with sexual transmission of the virus. HPV detection also appears to be an indicator of advanced disease characteristics that may require different clinical treatment for this subset of patients. An exfoliated oral cytology test for HPV was a significant predictor of HR types in the cancers, suggesting that an oral rinse may provide an early biomarker of infected tumors.     

Combined P16 and human papillomavirus testing predicts head and neck cancer survival

While its prognostic significance remains unclear, p16^INK4a protein expression is increasingly being used as a surrogate marker for oncogenic human papillomavirus (HPV) infection in head and neck squamous cell carcinomas (HNSCC). To evaluate the prognostic utility of p16 expression in HNSCC, we prospectively collected 163 primary tumor specimens from histologically confirmed HNSCC patients who were followed for up to 9.4 years. Formalin fixed tumor specimens were tested for p16 protein expression by immunohistochemistry (IHC). HPV type‐16 DNA and RNA was detected by MY09/11‐PCR and E6/E7 RT‐PCR on matched frozen tissue, respectively. P16 protein expression was detected more often in oropharyngeal tumors (53%) as compared with laryngeal (24%), hypopharyngeal (8%) or oral cavity tumors (4%; p < 0.0001). With respect to prognosis, p16‐positive oropharyngeal tumors exhibited significantly better overall survival than p16‐negative tumors (log‐rank test p = 0.04), whereas no survival benefit was observed for nonoropharyngeal tumors. However, when both p16 and HPV DNA test results were considered, concordantly positive nonoropharyngeal tumors had significantly better disease‐specific survival than concordantly negative nonoropharyngeal tumors after controlling for sex, nodal stage, tumor size, tumor subsite, primary tumor site number, smoking and drinking [adjusted hazard ratio (HR) = 0.04, 0.01–0.54]. Compared with concordantly negative nonoropharyngeal HNSCC, p16(+)/HPV16(?) nonoropharyngeal HNSCC (n = 13, 7%) demonstrated no significant improvement in disease‐specific survival when HPV16 was detected by RNA (adjusted HR = 0.83, 0.22–3.17). Our findings show that p16 IHC alone has potential as a prognostic test for oropharyngeal cancer survival, but combined p16/HPV testing is necessary to identify HPV‐associated nonoropharyngeal HNSCC with better prognosis.     

Prevalence of oral HPV infection among healthy individuals and head and neck cancer cases in the French West Indies

Purpose

Human papillomavirus (HPV) is known to play a role in the development of head and neck squamous cell carcinomas (HNSCC) and to date, no study has reported on the association between oral HPV infection and HNSCC in the Caribbean. The objective was to determine the prevalence of oral HPV infection in the French West Indies (FWI), overall and by HPV genotype, among HNSCC cases and healthy population controls.

Method

We used data from a population-based case–control study conducted in the FWI. The prevalence of oral HPV was estimated separately among 100 HNSCC cases (mean age 59 years) and 308 population controls (mean age 57 years). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using a logistic regression adjusting for age, sex, tobacco, and alcohol consumption, to assess the association between oral HPV infection and HNSCC.

Results

Prevalence of oral HPV infections was 26% in controls (30% in men and 14% in women) and 36% in HNSCC cases (36% in men, 33% in women). HPV52 was the most commonly detected genotype, in cases and in controls. The prevalence of HPV16, HPV33, and HPV51 was significantly higher in cases than in controls (p?=?0.0340, p?=?0.0472, and 0.0144, respectively). Oral infection with high-risk HPV was associated with an increase in risk of HNSCC (OR 1.99, 95% CI 0.95–4.15). HPV16 was only associated with oropharyngeal cancer (OR 16.01, 95% CI 1.67–153.64).

Conclusion

This study revealed a high prevalence of oral HPV infection in this middle-aged Afro-Caribbean population, and a specific distribution of HPV genotypes. These findings may provide insight into HNSCC etiology specific to the FWI.

     

Prevalence of type-specific human papillomavirus and pap results in Chinese women: a multi-center, population-based cross-sectional study

Purpose

To estimate the burden of human papillomavirus (HPV) infection among sexually active women in China.

Methods

We conducted a multi-center, population-based study between May 2006 and April 2007. A total of 4,215 women aged 17–54 years were surveyed from five geographical sites: Beijing, Shanghai, Shanxi, Henan, and Xinjiang. Direct endocervical exfoliated cells were collected from consenting participants for Sure Path liquid-based cytology (BD) and HPV testing. HPV testing was performed with Hybrid Capture II (Qiagen) with high-risk and low-risk probes, and Linear Array (Roche) was utilized for HPV genotyping.

Results

Approximately 11 % of the study population had a cytological abnormality (ASCUS or worse). HPV prevalence in the entire study population was 14.3 % (age-standardized to the world standard female population 14.5 %). The most prevalent types found were HPV16 (2.9 %), HPV52 (1.7 %), HPV58 (1.5 %), HPV33 (1 %), and HPV18 (0.8 %). Patterns of HPV prevalence differed by age, geographic region, and cytology findings. However, HPV16 was predominant among all grades of cytological abnormalities for all areas.

Conclusions

Although HPV18 appeared to be less frequent among population-based samples of China, given the high prevalence of HPV 16 and 18 in high-grade squamous intraepithelial lesion (HSIL) or worse pap abnormalities, prophylactic HPV16/18 vaccines should substantially reduce the burden of cervical cancer in China.     

Methylation of viral and host genes and severity of cervical lesions associated with human papillomavirus type 16

Methylation of human papillomavirus (HPV) and host genes may predict cervical cancer risk. We examined the methylation status of selected sites in HPV16 and human genes in DNA extracted from exfoliated cervical cell samples of 244 women harboring HPV16‐positive cancer or cervical intraepithelial neoplasia (CIN) or negative for intraepithelial lesions or malignancy (NILM). We quantified the methylation of CpG sites in the HPV16 L1 gene (CpG 6367 and 6389) and in the human genes EPB41L3 (CpG 438, 427, 425) and LMX1 (CpG 260, 262, 266, 274) following bisulfite treatment and pyrosequencing. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic utility of methylation level for the different sites and for a joint predictor score. Methylation in all sites significantly increased with lesion severity (p < 0.0001). Area under the curve (AUC) was highest among the CIN2/3 vs. cancer ranging from 0.786 to 0.853 among the different sites. Site‐specific methylation levels strongly discriminated CIN2/3 from NILM/CIN1 and cancer from CIN2/3 (range of odds ratios [OR]: 3.69–12.76, range of lower 95% confidence bounds: 1.03–4.01). When methylation levels were mutually adjusted for each other EPB41L3 was the only independent predictor of CIN2/3 vs. NILM/CIN1 contrasts (OR = 9.94, 95%CI: 2.46–40.27). High methylation levels of viral and host genes are common among precancerous and cancer lesions and can serve as independent risk biomarkers. Methylation of host genes LMX1 and EPB41L3 and of the viral HPV16 L1 sites has the potential to distinguish among precancerous lesions and to distinguish the latter from invasive disease.     

HPV16 variant lineage,clinical stage,and survival in women with invasive cervical cancer

Background

HPV16 variants are associated with different risks for development of CIN3 and invasive cancer, although all are carcinogenic. The relationship of HPV 16 variants to cancer survival has not been studied.

Methods

155 HPV16-positive cervical cancers were categorized according to European and non-European variant patterns by DNA sequencing of the E6 open reading frame. Clinico-pathologic parameters and clinical outcome were collected by chart review and death registry data.

Results

Of the 155 women (mean age 44.7 years; median follow-up 26.7 months), 85.2% harbored European variants while 14.8% had non-European sequences. HPV16 variants differed by histologic cell type (p = 0.03) and stage (1 vs. 2+; p = 0.03). Overall, 107 women (68.0%) were alive with no evidence of cancer, 42 (27.1%) died from cervical cancer, 2 (1.3%) were alive with cervical cancer, and 4 (2.6%) died of other causes. Death due to cervical cancer was associated with European variant status (p < 0.01). While 31% of women harboring tumors with European variants died from cervical cancer during follow-up, only 1 of 23 (4.4%) non-European cases died of cancer. The better survival for non-European cases was partly mediated by lower stage at diagnosis.

Conclusions

Overall, invasive cervical cancers with non-European variants showed a less aggressive behavior than those with European variants. These findings should be replicated in a population with more non-European cases.

     

Prevalence of HPV infection in hypopharyngeal and laryngeal squamous cell carcinoma at Thailand's largest tertiary referral center

Background

Following the well-established relationship between human papillomavirus (HPV) and cervical carcinoma, the carcinogenicity of this virus has also been confirmed in subsets of head and neck carcinoma (HNCA), but mainly in the oropharynx. Other subsites of HNCA with less known association to HPV have never been studied in Thailand. Accordingly, the aim of this study was to investigate the prevalence of HPV DNA in hypopharyngeal and laryngeal squamous cell carcinoma in Thai population.

Methods

This cross-sectional study included hypopharyngeal and laryngeal squamous cell carcinoma patients diagnosed and treated at the Department of Otorhinolaryngology, Siriraj Hospital during the September 2011–December 2013 study period. Presence of HPV genome was confirmed by polymerase chain reaction from pathologically-confirmed fresh specimens. Demographic data and risk factors of HPV infection were evaluated.

Results

Eighty patients were included, and 95% of those were male. Only one patient was noted with positive HPV-62 serotype. Most patients consumed tobacco and/or alcohol. Five patients had no risk factors for cancer development. Risk of HPV infection was evaluated by self-reporting questionnaire. The mean age of sexual debut was 20.17 years. Forty-eight patients had multiple sexual partners. Sixteen and seven patients had history of sexually transmitted disease infection and habitual oral sex contact, respectively.

Conclusion

There was no oncogenic HPV DNA detected within pathologic specimens of laryngeal and hypopharyngeal cancers in this study. Compared to rates reported from developed countries, the prevalence of HPV-related HNCA in Thailand is very low.

     

Prevalence of Human papillomavirus (HPV) and Epstein-Barr virus (EBV) in oral and oropharyngeal squamous cell carcinoma in south-eastern Poland

Objective

The aim of this study was to analyze the prevalence of HPV and EBV in oral and oropharyngeal squamous cell carcinoma in south-eastern Poland. The correlation between viral infection, OSCC, alcohol use, tobacco smoking, demographic data (gender, age, place of residence), anatomic location, pre-treatment staging, evidence of metastases to lymph nodes, and grading was also investigated.

Methods

The examination samples were collected from paraffin tissue blocks, from 154 patients. Viral DNA was amplified by the nested-PCR method.

Results

HPV DNA was detected in 29.2 % of the tested samples (in 27.4 % of oropharyngeal and in 30.4 % of oral cavity). The HPV type 16 was detected in 15.6 % of all samples, and in 53.3 % of HPV-positive group. In HPV-positive samples from oropharyngeal HPV 16 constitute 76.5 %, and in HPV-positive samples from oral cavity HPV 16 constitute 39.3 %. Mixed infection (more than one type of HPV) was observed in 23.5 and 60.7 %, respectively, and in 46.7 % of all HPV-positive samples, and in 12.3 % of the whole study group. EBV DNA was detected in 27.3 % of the cases and HPV-EBV co-infection in 7.8 % of samples.

Conclusions

In major patients from Southeastern region of Poland with oropharyngeal cancer HPV type 16 was detected but in oral cavity cancer other mixed infections were observed (i.e. 51, 52, 59, 66, 68, 71, 74). HPV 16 was detected more often among patients younger than 50 years of age, whereas the mixed HPV in the group aged 50–59. The pathogenesis of oral squamous cell carcinoma may be connected with EBV infection. Future studies on the mechanisms of HPV/EBV co-infection and/or superinfection and their role in oral squamous cell carcinoma are necessary.

     

Risk factors and survival by HPV‐16 E6 and E7 antibody status in human papillomavirus positive head and neck cancer

High‐risk human papillomavirus types (HPV‐HR) are associated with head and neck cancer (HNC) risk and better survival. Most patients with HPV‐HR DNA‐positive tumors develop anti‐HPV E6/E7 antibodies; however, it is unclear whether those who mount an immune response have similar risk factors or clinical outcomes as those who do not. HPV‐16 DNA tumor‐positive HNC cases were evaluated for HPV‐16 E6 and E7 antibodies using a GST capture ELISA system. Among 57 HPV‐16 DNA tumor‐positive HNC cases, 67% were detected with HPV‐16 E6 and/or E7 antibodies. Male gender (76% vs. 42%, p = 0.02), younger age (63% vs. 16%, p = 0.001) but not tobacco or alcohol were associated with E6 and/or E7 seropositivity. Seropositivity was associated more often with late stage (76%), poor grade (65%), positive nodes (82%). and in the oropharynx (82%), Median disease‐specific and recurrence‐free survival were longer in E6 and/or E7 seropositive compared to E6/E7‐negative cases (2.2 years vs. 1.4 years, both outcomes), although results were not statistically significant. When examined jointly with p16 expression, E6 and/or E7‐positive/p16‐positive cases had better disease‐specific (2.1 years vs. 1.1 years, p = 0.06) and recurrence‐free (2.3 years vs. 1.1 years, p = 0.03) survival compared to E6‐/E7‐/p16‐ cases. These findings suggest there are 2 distinct HNC patient groups with HPV DNA‐positive tumors, distinguishable by E6 and/or E7 antibody status. Differences in antibody status are associated with distinct risk factors and clinical outcomes. This information can be available as a simple blood test at initial presentation, before the removal of tissue through biopsy or surgery.     

Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology,ASCUS/LSIL,HSIL, or cervical cancer: what is the potential for prevention?

Background

Assessment of the prevaccination type-specific prevalence of human papillomavirus (HPV) in the general population is important for the prediction of the impact of HPV vaccination.

Methods

We collected consecutively residual specimens from liquid-based cytology samples from 40,382 women from the general population in Copenhagen, Denmark, during 2002–2005. All samples were tested for high-risk HPV using the Hybrid Capture 2 technique, and genotyping was done using LiPa (Innogenetics). Through linkage with the Pathology Data Bank, we obtained information on the cytology result, and histology if any, on all women.

Results

The participants were 14–95 years of age (median age 37 years) at enrollment. The overall prevalence of HR HPV was 20.6 % ranging from 46.0 % in 20–23-year-old women to 5.7 % in women 65 years or older. Independently of cytology/histology, HPV16 was the most prevalent type. For virtually all HPV types, the occurrence of CIN3+ was higher when the specific HPV type was present together with HPV16 than it was together with other high-risk HPV types than HPV16 or if the HPV type occurred as a single infection. The prevalence of HPV16 and/or HPV18 was 74 % in cervical cancer and the corresponding prevalence of HPV16/18/31/33/45/52/58 was 89 %.

Conclusion

This study forms a valuable starting point for monitoring the effect of HPV vaccination in Denmark. In addition, the particular carcinogenic role of HPV16 and 18 is confirmed and may support a role of genotyping for HPV16 and 18 in cervical cancer screening.