Determination of Role of Type 16 Human Papillomavirus and Risk Factors in Assessing Oropharyngeal Cancer Survival

Abstract

Background:

It is ascertained that the survival rate of patients infected with type 16 human papillomavirus (HPV16) positive is better as compared to those infected with HPV16 negative. The present study was conducted to determine rgw role of HPV16 and risk factors in assessing oropharyngeal cancer (OPC) death.

Methodology:

A total of 102 clinically and histologically proven cases of oral pharyngeal cancer were included. Seropositivity for HPV16 E6 as a marker of HPV16-positive cancer was estimated.

Results:

Out of 102 patients, there were 70 males and 32 females. Significant risk factors associated with OPC survival overall in the univariate analysis was female sex (hazard ratio [HR] 0.54, 95% confidence level [CL]: 0.36–80), alcohol use >2 drinks/day (HR 1.54, 95% CL: 1.12–2.08), smoking >10 pack-years (HR 2.20, 95% CL: 1.42–3.58), moderate dental (HR 1.54, 95% CL: 1.02–2.32), underweight (HR 2.24, 95% CL: 1.34–3.60), and Stage IV cancer (HR 2.82, 95% CL: 1.76–4.40). There was significant low risk for death among HPV16 positive (HR 0.48, 95% CL: 0.32–0.70).

Conclusion:

HPV16 status is an independent prognostic factor for OPC deaths. The common risk factors were female gender, moderate oral care, underweight body mass index, excessive alcohol, and smoking tobacco.

INTRODUCTION

The number of oral pharyngeal cancer is on rise since the last couple of years. It has high mortality and morbidity.[1] It is evident that the main etiological factor in these cases is tobacco and alcohol. Tobacco is consumed in both smoking and smokeless form. Smoking tobacco is the main reason for causing oral cancer.[2] Bidi, cigarette, hookah, hooki, etc., are smoking form of tobacco, whereas gutka, mawa, mishri, pan supari, etc., are smokeless forms. The role of alcohol is synergistic with its ability to cause dryness of oral mucosa, which increases the chances of carcinogen penetration.[3] Apart from these agents, type 16 human papillomavirus (HPV16) in causing oropharyngeal cancers (OPCs) cannot be underestimated. Few cases of cancer involving soft palate, tonsils, tongue, and oropharynx have been found associated with HPV16. Cancer of buccal mucosa is mostly associated with smokeless form of tobacco.[4]

Two different forms of HPV16 occur such as HPV16+ and HPV16−.[5] It is further ascertained that the survival rate of patients infected with HPV+ is better as compared to those infected with HPV−. It is found that HPV DNA and p16 expression determine the HPV status. History of smoking and disease stage help in differentiating patients into prognostic groups.[6] The present study determined role of HPV16 and risk factors in assessing OPC death.

METHODOLOGY

The present study comprised 102 clinically and histologically proven cases of oral cancer found in both genders. Cases were enrolled after all agreed to participate in the study.

Demographic data consisted of information such as name, age, and gender. A thorough oral examination was performed. Cancer staging was done and patients were classified into smokers or nonsmokers. Frequency and amount of alcohol consumption (ml) were recorded. Body mass index (BMI) was also determined on the basis of formula (weight [kg] × height [m²]). Patients were classified into normal, underweight, overweight, and obese based on BMI.

Venous blood sample was obtained for the estimation of antibodies to HPV16 E6. HPV genotyping was executed with type-specific E7 polymerase chain reaction bead-based multiplex assay. Results were clubbed together and subjected to statistics for assessing significance of the data based on hazard ratios (HRs) and confidence intervals (CIs).

RESULTS

Table 1 shows that out of 102 patients, there were 70 males and 32 females.

Table 1.

Distribution of patients

Gender	n
Male	70
Female	32
Total	102

Table 2 shows that the significant risk factors associated with OPC survival overall in the univariate analysis were female sex (HR 0.54, 95% CL: 0.36–80), alcohol use >2 drinks/day (HR 1.54, 95% CL: 1.12–2.08), smoking >10 pack-years (HR 2.20, 95% CL: 1.42–3.58), moderate dental (HR 1.54, 95% CL: 1.02–2.32), underweight (HR 2.24, 95% CL: 1.34–3.60), and Stage IV cancer (HR 2.82, 95% CL: 1.76–4.40). There was significant low risk for death among HPV16 positive (HR 0.48, 95% CL: 0.32–0.70).

Table 2.

Analysis of risk factors in patients

Variables	Characteristics	Dead/total	Univariate, HR (95% CL)	Multivariate, aHR (95% CL)
Gender	Male	42/70	1.0	1.0
	Female	17/32	0.54 (0.36-80)	0.52 (0.30-82)
HPV16 E16 serology	Positive	26/40	0.48 (0.32-0.70)	0.52 (0.34-0.84)
	Negative	33/62	1.0	1.0
Alcohol use (drinks/days)	>2	20/30	1.54 (1.12-2.08)	1.03 (0.70-1.52)
	<2	39/74	1.0	1.0
Smoking (pack years)	>10	34/44	2.20 (1.42-3.58)	1.10 (0.60-2.08)
	<10	25/58	1.0	1.0
Dental care	Good	13/28	1.0	1.0
	Moderate	42/68	1.54 (1.02-2.32)	1.10 (0.74-1.64)
	Poor	4/6	2.42 (0.74-7.92)	0.42 (0.08-3.42)
BMI	Normal	14/27	1.0	1.0
	Underweight	25/30	2.24 (1.34-3.60)	2.42
	Overweight	20/45	1.04 (0.72-1.40)	1.14 (0.76-1.64)
Stage	I and II	20/38	1.0	1.0
	III	26/40	2.04 (1.20-3.40)	1.76 (1.36-4.22)
	IV	13/24	2.82 (1.76-4.40)	2.62 (1.60-4.32)

HR: Hazard ratio, BMI: Body mass index, aHR: Adjusted HR, HPV: Human papillomavirus

DISCUSSION

OPC contributes to significant death among various cancers of body.[7] The high use of tobacco among males and females is the leading cause of cancers.[8] It is observed that smoking form of tobacco such as bidi and cigarette increases the risk of cancer.[9] The present study was conducted to determine role of HPV16 and risk factors in assessing OPC death.

In the present study, we found that out of 102 patients, there were 70 (68.6%) males and 32 (31.4%) females. A study by Anantharaman et al.[10] determined factors linked with the outcome of OPC in 321 patients and attempted to consider seropositivity for HPV16 E6 for HPV16-positive cancer marker. The results of the present study demonstrated that there was 50% overall 5-year survival rate in patients. Results revealed that patients diagnosed with HPV16 positive had relatively and significantly low chances of mortality as compared to those diagnosed with HPV16 negative having HR of 0.51 and 95% confidence interval (CI) range of 0.32–0.80. Female gender exhibited a considerable effect on OPC survival with 0.50 HR and 0.29–0.85 95% CI. Similarly, underweight at diagnosis (adjusted HR [aHR]: 2.41, 95% CI: 1.38–4.21) showed effect on OPC survival. Results further showed that a 10-pack–year smoking history was not linked with overall survival (OS). It was observed that Stage III and IV look as the predominant factors significantly related with OPC recurrence (aHR: 4.88, 95% CI: 2.12–11.21).

In the present study, we found that significant risk factors associated with OPC survival overall in the univariate analysis were female sex (HR 0.54, 95% CL: 0.36–80), alcohol use >2 drinks/day (HR 1.54, 95% CL: 1.12–2.08), smoking >10 pack years (HR 2.20, 95% CL: 1.42–3.58), moderate dental (HR 1.54, 95% CL: 1.02–2.32), underweight (HR 2.24, 95% CL: 1.34–3.60), and Stage IV cancer (HR 2.82, 95% CL: 1.76–4.40). We found that there was significant low risk for death among HPV16 positive (HR 0.48, 95% CL: 0.32–0.70). Meng et al.[11] evaluated the association of p16 with OPC in 1470 patients. Results of the study showed that the expression of p16 was present in 5.51% (81) and HPV positive was present in 5.31% (78) of cases. Authors found a positive association between HPV-positive patients and p16 overexpression. It was found that smokers constituted approximately 89% of patients and approximately 70% of patients with p16 expression had the habit of alcoholism. Authors found that early-stage primary oropharyngeal squamous cell carcinomas (OPSCCs) is relatively linked with p16 expression, and similarly, patients with p16 expression showed good survival after being treated with surgery and radiotherapy.

Amini et al.[12] conducted a study by involving 3952 patients out of which 2454 (62%) were HPV positive. Study revealed overall survival rate of 93.1% in HPV positive patients and 77.8% in HPV negative patients. Multimodality treatment comprised chemoradiotherapy (CRT) and Surgery + Radiotherapy but not S-CRT as predictors for improved OS in HPV-positive Stage III–IVB disease. Results further demonstrated that Surgery + Chemotherapy + Radiotherapy was coupled with longer OS in HPV-negative OPSCC-positive patients during multimodality treatment. Similarly, a poor association was observed between lymph node stage with OS in HPV-positive cancers. It was found that the occurrence of positive margins and/or extracapsular extension was connected with worse OS in HPV negative with HR of 2.11 and with significant difference having P = 0.008 but not HPV-positive OPSCC patients (HR 1.61, P = 0.154).

The shortcoming of the study is small sample size.

CONCLUSION

Authors found that HPV16 status is an independent prognostic factor for OPC deaths. Common risk factors were female gender, moderate oral care, underweight BMI, excessive alcohol, and smoking tobacco.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.