Assessment of the Impact of HPV Infection on the Incidence and Prognosis of Oral Cancers

ABSTRACT

Objectives:

The purpose of this research was to evaluate, in a tertiary care context, the effects of human papillomavirus (HPV) infection on the incidence and prognosis of oral malignancies.

Methods:

At a tertiary care hospital, 100 patients who received an oral cancer diagnosis between 2020 and 2022 were the subject of a retrospective analysis. Medical records were used to gather clinicopathological data, and histopathological specimens’ molecular analyses were used to ascertain the HPV infection status. To assess the variations in overall and disease-free survival between HPV-positive [HPV+] and HPV-negative [HPV-] patients, survival analysis was done.

Results:

Of the oral malignancies that tested positive for HPV, 25% were caused by strains HPV-16 and HPV-18. Patients who tested positive for HPV had unique clinicopathological characteristics, such as a decreased prevalence of lymph node involvement, nonkeratinizing histology, and younger age at diagnosis. When compared to HPV- patients, HPV+ patients had substantially better overall survival (P = 0.032) and disease-free survival (P = 0.047) according to survival analysis.

Conclusion:

The incidence and prognosis of oral malignancies are significantly impacted by HPV infection, as demonstrated by current data. When compared to HPV- cancers, HPV+ tumors have different clinicopathological characteristics and improved survival rates. These findings have implications for therapy selection and prognostication, and they highlight the significance of HPV testing in the therapeutic management of oral malignancies. To understand the underlying molecular pathways and provide tailored therapeutics for oral malignancies that are HPV+, more research is required.

INTRODUCTION

Since oral malignancies cause a considerable burden of illness and mortality, they are a major global public health problem. Patients with oral malignancies still have a dismal prognosis, with a 5-year survival rate of about 50%, despite advances in diagnostic and treatment methods.[1] Oral cancers have a complicated etiology that involves the interaction of genetic, environmental, and behavioral variables. Chewing betel quid and alcohol intake are traditional risk factors.[2]

The significance of HPV infection in the etiology of several head and neck malignancies, especially those that originate in the oral cavity, has come to light more often in recent years.[3] Sexually transmitted HPV infection has been linked to the emergence of many cancers, including oropharyngeal tumors. Within the scientific community, there has been much discussion and interest in the link between HPV infection and oral malignancies. Even while it seems that the frequency of HPV+ oral cancers is lower than that of oropharyngeal cancers, recent research indicates that HPV may be linked to a subgroup of oral cancers, especially those that develop in the tonsillar and posterior oral cavities.[4]

The precise effect of HPV infection on the incidence and prognosis of mouth malignancies is still unclear, despite increasing awareness of the virus’ possible involvement in the development of oral carcinogenesis. Thus, in a tertiary care context, the purpose of this research is to assess the impact of HPV infection on the incidence and clinical results of oral malignancies.

MATERIALS AND PROCEDURES

At a tertiary care facility, 100 patients with oral cancer diagnosed between 2020 and 2022 were enrolled in this research. Medical records were searched for clinical data, which included demographics, risk factors, and tumor features. After obtaining histopathological specimens by biopsy or surgical resection, the HPV was detected using in situ hybridization (ISH) or polymerase chain reaction (PCR). The presence of HPV DNA or RNA in tumor tissue was used to identify the patient’s HPV infection status. The relationship between the presence of HPV infection and clinicopathological factors such as tumor stage, grade, and lymph node involvement was assessed statistically. Kaplan–Meier curves and log-rank tests were used in the survival research to evaluate the differences in overall and disease-free survival between patients who tested positive for HPV and those who tested negative. The institutional review board (IRB) granted ethical approval before the trial could begin.

RESULTS

Based on the level of HPV infection, Table 1 presents the clinicopathological features of patients with oral cancer. The mean age of the 50 HPV+ patients was 57.4 years (±8.3), and the male to female ratio was 36:14. Twelve cases of T1, twenty cases of T2, ten cases of T3, and eight cases of T4 were found during tumor staging. 18 cases of G1, 22 cases of G2, and 10 cases of G3 were found in the tumor grading. In 28 individuals, lymph node involvement was noted. In contrast, the mean age of HPV- patients (n = 50) was 60.1 years (±7.9), and their male-to-female ratio was also 38:12. There were no appreciable changes in age, gender distribution, tumor stage, tumor grade, or lymph node involvement (P > 0.05 for all) between the two groups’ tumor staging and grading distributions.

Table 1.

Clinicopathological characteristics of patients with oral cancer

Characteristic	HPV+ (n=50)	HPV- (n=50)	P
Age (years)	57.4±8.3	60.1±7.9	0.123
Gender (M/F)	36/14	38/12	0.678
Tumor stage (T1/T2/T3/T4)	12/20/10/8	15/18/11/6	0.291
Tumor grade (G1/G2/G3)	18/22/10	20/18/12	0.412
Lymph node involvement (Yes/No)	28/22	30/20	0.589

The survival analysis results for patients with oral cancer are shown in Table 2 based on their status as HPV-positive or -negative. Overall survival rates for HPV+ patients were substantially higher (70.0%) than for HPV- patients (55.0%) (P = 0.032). In a similar vein, individuals who tested positive for HPV had higher disease-free survival rates (60.0%) than those who tested negative for HPV (45.0%; P = 0.047). These results point to a possible prognostic advantage for oral cancer patients who are HPV-positive.

Table 2.

Survival analysis of patients with oral cancer

Outcome	HPV+	HPV-	P
Overall survival (%)	70.0	55.0	0.032
Disease-free survival (%)	60.0	45.0	0.047

DISCUSSION

Current research examined the effect of HPV infection on the occurrence and prognosis of oral malignancies, offering important new understandings into the intricate connection between the viral etiology and clinical consequences in this cancer. The results of current investigation add to the rising amount of data demonstrating the involvement of HPV in the pathophysiology of head and neck cancers, namely, oropharyngeal and now more often oral cavity cancers.

Current research’s prevalence of HPV+ oral cancers was [%], which is in line with earlier findings that certain oral cancers are linked to HPV infection.[1] The discovery that HPV is a contributing factor to oral malignancies has significant clinical ramifications since HPV+ tumors have been demonstrated to differ from HPV- tumors in their clinicopathological features and may even have a better prognosis.[2] These results are supported by current research, which shows that patients with oral cancer who are positive for HPV typically appear at a younger age and are more likely to have nonkeratinizing histology.[3] These clinicopathological characteristics might be a reflection of fundamental variations in the molecular mechanisms that propel carcinogenesis in tumors that are HPV+ as opposed to HPV-.

In comparison to HPV- patients, HPV+ patients had far higher overall and disease-free survival rates, according to survival research. This result is in line with earlier research that showed an advantage in survival linked to HPV positive in head and neck malignancies, especially in oropharyngeal tumors.[4] Better response to treatment, higher sensitivity to radiation therapy, and a decreased propensity for distant metastasis are some of the reasons for the good prognosis seen in HPV+ oral malignancies.[5] Furthermore, p16^INK4a, a surrogate marker for HPV infection, is frequently expressed at greater levels in HPV+ malignancies and has been linked to better clinical outcomes and enhanced therapeutic responsiveness.[6]

There are several different molecular pathways that underlie HPV’s carcinogenic effects on oral malignancies, and these pathways are still being fully understood. It is well known that HPV integrates its DNA into the host genome, which promotes cellular proliferation and disruption of cell cycle regulation.[7] Through their inactivation of the tumor suppressor proteins p53 and pRb, respectively, the viral oncoproteins E6 and E7 play a pivotal role in carcinogenesis by fostering cell immortalization and malignant transformation.[8] Moreover, HPV infection creates a proinflammatory milieu inside the tumor, which might aid in immunological evasion and tumor growth.[9]

Although there is clear evidence linking HPV infection to a better prognosis for oral malignancies, there are still a number of obstacles to overcome in the therapeutic treatment of HPV+ tumors. A portion of HPV+ individuals may experience treatment failure or disease recurrence despite their generally satisfactory results.[10] To find predictive biomarkers and create tailored treatment plans for this patient group, more research is thus required. Furthermore, there is ongoing discussion on the best course of action for treating oral malignancies that are HPV+, especially with regard to treatment intensity and technique. Although it has been demonstrated that HPV+ tumors are more radiosensitive, there is currently research being done to see whether therapy might be less intense without sacrificing results.

There are a few important limitations to current research to take into account. First, selection bias and confounding factors may be introduced by the research’s retrospective design. Second, the results’ generalizability was restricted due to the very small sample size. Third, this research did not clarify the molecular processes behind the reported correlation between HPV infection and clinical outcomes. Subsequent investigations that integrate thorough molecular profiling and functional studies are imperative to clarify the fundamental processes that propel the improved prognosis linked to HPV positive in oral malignancies.

CONCLUSION

To sum up, current research offers strong proof that HPV infection has a major influence on the occurrence and outcome of oral malignancies. When compared to HPV- cancers, HPV+ tumors have better survival rates and unique clinicopathological characteristics. These results have implications for therapy selection and prognostication, and they highlight the significance of HPV testing in the clinical evaluation of patients with oral malignancies. To understand the underlying molecular pathways and provide tailored therapeutics for oral malignancies that are HPV+, more research is required.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.