Markers of HPV infection and survival in patients with head and neck tumors

Abstract

The purpose of this study was to determine whether changes in human papillomavirus (HPV) DNA prevalence in oral rinses and/or HPV-specific antibody levels in the sera of patients with oral/oropharyngeal cancer have prognostic significance. One hundred and forty-two patients with oral/oropharyngeal tumors were enrolled. The presence of HPV DNA was assayed in tumor tissue and oral rinses and HPV-specific antibodies were assessed in the sera. Oral rinses were collected before treatment and one year after the treatment. Sera were drawn before treatment, one month, and one year after the end of the treatment. Altogether, 59.2% of tumors were HPV positive. The presence of HPV DNA in the tumors correlated with HPV DNA positivity in oral rinses and with HPV-specific antibodies in the sera. Out of 66 patients with HPV-positive oral rinses at enrolment, 84.8% became negative at one-year follow-up, while most patients remained seropositive for HPV-specific antigens. However, the mean titers of HPV16 E6 and/or E7 antibodies at follow-up were significantly lower. Of 16 patients with recurrences at followup (alive on second sampling), six were positive at enrolment for HPV16 E6 and/or E7 antibodies. In five of these, no decrease in antibody levels was observed. Titers of antibodies specific for HPV16 capsid antigens did not change during the follow-up. Our data suggest that the detection of antibodies specific for the HPV 16 E6 and E7 oncoproteins may serve not only as a marker of HPV etiology, but also as a marker of recurrence and a prognostic indicator in patients with HPV-positive tumors.Squamous cell carcinoma of the head and neck (SCCHN) accounts annually for 7% of all new cancer cases worldwide. 1 SCCHN presents as a single clinical and pathological entity, yet studies conducted over the past 15 years have revealed that it has two distinct etiologies. Most SCCHN cases, particularly those located in the oral cavity, larynx, and hypopharynx, are apparently independent of viral infection, and often associated with tobacco and alcohol use. However, 26% of all SCCHN cases, and over 70% of those found in the tonsillar area and oropharynx, are associated with the presence and expression of mucosal high-risk (oncogenic) human papillomavirus (HR HPV) genomes. [2][3][4] HR HPVs cause cervical cancer and other neoplasms of the anogenital skin and mucosae. 5,6 The most common genital mucosal HR HPV type 16, is found in 95% of HPVpositive SCCHN lesions. 7,8 Although patients with HR HPVassociated SCCNH often present with more advanced disease, we and others have shown that these patients have a remarkably better prognosis and five-year survival rate. 2,9-11 The prognostic advantage of patients with SCCHN etiologically linked to HR HPV could potentially lead to modified treatment regimens. Therefore, noninvasive or less invasive sampling procedures to identify patients with HPV-positive tumors were evaluated in several studies including ours. 12-16It has been demonstrated that the presence of HPV DNA in oral rinses or saliva as well...

Prognostic Implication of Persistent Human Papillomavirus Type 16 DNA Detection in Oral Rinses for Human Papillomavirus–Related Oropharyngeal Carcinoma

“…This may also explain the high rate of newly detected non-HPV16 HR-HPV DNA after treatment, which was also noted in previous studies. 12,14 Our finding that HPV16 viral load in oral rinses at diagnosis was associated with worse survival has not to our knowledge been previously reported, and the clinical relevance is unclear because there were few events in our study. It is possible that higher viral copy number may correlate to some measure of disease activity, for example, tumor size, and portend increased resistance to treatment.…”

“…A potential strategy to increase sensitivity for recurrence overall is to combine oral rinses with plasmabased testing for HPV16 biomarkers, such as HPV16 DNA or antibodies to HPV16 antigens, which has also been shown to be sensitive for HPV-OPC and is less anatomically constrained. 11,14,22 The prognostic value of persistent oral HR-HPV DNA detection in posttreatment oral rinses was limited in our study to HPV16, whereas persistence of other HR-HPV types was not associated with recurrence or survival. Because HPV16 is responsible for more than 90% of HPV-OPCs, 23,24 DNA from other HR-HPV types is less likely to be etiologically related to tumor recurrence.…”

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

“…showed that high HPV viral load increased the odds of HPV16 E6 seropositivity 57‐fold and HPV16 E7 seropositivity 26‐fold. Moreover, HPV16 E6 antibodies have also been shown to be independent favourable prognostic factors in OPCs 49, 50. Some HPV‐related OPCs are mediated by other HPV genotypes, including HPV18 (1–8% of OPCs), and less commonly HPV33, −35, −56 and −67 51.…”

Molecular characterization of human papillomavirus in head and neck tumors.

“…I also observed that sera that were seronegative before treatment remained so after treatment of patients. In addition, some studies have suggested that HPV16 E6/E7 seropositivity is prognostic of a favorable clinical outcome of HNC patients (156,163 in our study population, possibly secondary to the strikingly high smoking prevalence. Indeed, some cases of HNC may be caused by a combination of tobacco and HPV (164).…”

“…Serial monitoring of HPV serology may also be useful in predicting a patient's response to treatment. The decline of anti-HPV16 E6 and/or E7 antibodies after treatment has been shown in cervical cancers (159)(160)(161) and with a few studies in HNC (156,157). From our laboratory, Drs.…”