HPV16 semiquantitative viral load and serologic biomarkers in oral and oropharyngeal squamous cell carcinomas

Abstract

A considerable subset of oropharyngeal squamous cell carcinomas (SCCs) are positive for human papillomavirus (HPV); however, delineating etiologically-associated HPV infections from SCCs with concurrent HPV infection unrelated to tumorigenesis is challenging. Viral load assessment in biopsy specimens may help facilitate such differentiation. HPV16 viral load and serologic markers were assessed among oral and oropharyngeal cases from a multinational study conducted by the International Agency for Research on Cancer (IARC). HPV16 viral load, measured semiquantitatively by PCR-enzyme immunoassay, was dichotomized as high or low based on the median optical density value. Serologic antibodies to HPV16 virus-like particles (VLPs) and to HPV16 E6 and E7 proteins were measured by ELISA. Compared to HPV DNA-negative cases (n = 852), HPV16 DNA-positive cases with high viral load (n = 26) were significantly more likely to originate in the oropharynx (odds ratio [OR], 12.0; 95% confidence interval [CI], 5.2-27.5) and, after adjustment for tumor site (AdjOR), have antibodies against HPV16 VLPs (AdjOR, 14.6; 95% CI, 6.0-35.6), E6 (AdjOR, 57.6; 95% CI, 21.4-155.3) and E7 (AdjOR, 25.6; 95% CI, 9.3-70.8). HPV16 DNA-positive cases with low viral load (n = 27) were more commonly oropharyngeal (OR, 2.7; 95% CI, 1.1-6.2) and seropositive for HPV16 VLPs (AdjOR, 2.7; 95% CI, 1.1-6.9), E6 (AdjOR, 3.0; 95% CI, 0.7-14.0) and E7 (AdjOR, 3.5; 95% CI, 0.7-16.3), compared to HPV DNA-negative cases; the associations, however, were neither as strong nor as significant as the associations for high viral load. As there appears to be a strong association between HPV16 serologic markers and viral load, in the absence of data on serologic markers, HPV16 viral load may be used to help delineate the subset of HPV16 DNA-positive oral and oropharyngeal cancers that may be the consequence of HPV infection. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; HPV16 viral load; oral cancer; oropharyngeal cancer Numerous studies have provided consistent evidence that human papillomavirus (HPV), the necessary cause of cervical cancer, is present in tumor biopsies from approximately 20-50% of oropharyngeal squamous cell carcinomas (SCCs) and a smaller subset of oral SCCs. 1-4 Among HPV DNA-positive oropharyngeal SCCs, 90% are positive for HPV16. 1-4 Nonetheless, HPV DNA detection in tumor biopsies may not be sufficient evidence of causation. HPV16 DNA from tumor specimens analyzed jointly with markers of expression of the viral oncogene E6, mutational patterns of the cancer suppressor gene TP53 and levels of allelic loss, have helped identify a subset of these cancers that may be the consequence of HPV infection. 1,2,[5][6][7][8] HPV viral load, a measure of the amount of viral DNA in biopsy specimens, alone or in conjunction with well-characterized HPV serologic assays, may clarify the role of HPV among oral and oropharyngeal cases. Antibodies against HPV E6 and E7 are markers of an invasive HPV-associated malignancy 9,10 and are rarely present among ind...

Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all‐cause mortality: Results from head and neck 5000, a prospective observational cohort of people with head and neck cancer

“…Previous studies have confirmed, however, that detection of antibodies against E6 and E7 oncoproteins shows good correlation with HPV DNA in the tumour tissue 32. Kreimer et al .…”

Oral squamous cell carcinoma: Review of prognostic and predictive factors

“…There is escalating evidence of a causal association between HPV and OSCC, [82][83][84][85][86][87][88][89][90][91][92][93] with several studies showing that HPV is associated with increased risk of oral cancer, independently of exposure to tobacco and alcohol. 84,86,88,89 This association is valid for high-risk HPV, which comprises subtypes 16, 18, 33, and 35.…”

“…HPV-16 may be responsible for more than 80% of HPV-positive OSCC. 82,83,[85][86][87][88]90,93 The virus can be detected in tissues or cells using several methods, namely, biochemical, immunologic, microscopic, and molecular. Polymerase chain reaction is considered the most sensitive assay.…”

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

“…In all cultures, both CD8þ and CD4þ T cells grew out (CD4/CD8 ratio median 2.45, average 5.1 and range 0. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The composition of T cells was not clearly influenced by the culture conditions (Fig.…”

“…8 In addition, circulating antibodies to HPV16 have been detected in HNCSCC patients with high viral load and it is suggested that the HPV-specific antibody status is related to clinical outcome. 9,10 In nonviral-induced, smoking and drinking-associated HNCSCC, p53 overexpression is one of the most common abnormalities identified. Mutation of p53 is correlated with poor prognosis.…”