The Role of Human Papillomavirus in Oral Squamous Cell Carcinoma (Review)

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The role of human papillomavirus in oral squamous cell carcinoma

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Department of Oral and Maxillofacial-Caput and Cervix Surgery, Academy Hospital Infanta Cristina, 06080 Badajoz, Spain.

Correspondence Address: Dr. Francisco A. Ramírez-Pérez, Section of Oral and Maxillofacial Surgery, University Hospital Infanta Cristina, Avenida de Elvas s/n, 06080 Badajoz, Spain. E-mail: francisco_alejandro_1987@hotmail.com

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Received: 1 Apr 2016 | Accepted: 17 May 2016 | Published: 25 May 2016

Abstract

Aim: The causative role of human papillomavirus (HPV) has been established into the aetiology of oral squamous jail cell carcinoma (OSCC). Some authors believe that HPV can determinate the prognosis and module treatment response from this kind of malignancies.

Methods: Articles published in the concluding 10 years, focusing on the role of HPV in the evolution, molecular biology, prognosis and treatment of OSCC were reviewed.

Results: Thirty-nine articles from 252 were selected, highlighting 4 meta-assay, 3 prospective and two retrospective studies. According to its role in the development of cervical cancer, HPV is classified into a high risk for malignant lesions subtype and a low-grade malignant lesions subtype. Epidemiology and prevalence of HPV varies co-ordinate to the published data: big studies tend to take lower rates of HPV (< 50%) than smaller ones (0-100%). Interestingly, HPV+ patients are usually diagnosed at a younger age, mainly those with oropharyngeal tumours. There is a predilection for the oropharynx and Waldeyer band tumours. Regarding prognosis, OSCC HPV+ patients tend to have better consequence and handling response.

Conclusion: HPV divides OSCC in two types of tumours with different prognostic and therapeutic implications, with increased survival, better treatment response rates and lower gamble of decease and recurrences.

Keywords

Papillomavirus infections, carcinoma squamous cell, mouth

Introduction

Squamous jail cell carcinoma (SCC) is the most common malignant lesion of the oral cavity and oropharynx. It is characterized past a multifactorial aetiology,^[1-5] where the causative office of papillomavirus (HPV) has been established.^[6] It is sexually acquired,^[7] usually described in the tonsillar area,^[8-10] affecting younger, non-drinkers and not-smokers patients.^[11-13] DNA from virtually oncogenic chance HPV is detected in approximately 26% of all oral squamous cell carcinoma (OSCC) throughout the world.^[14]

The appearance of this kind of tumours has changed among the terminal decades. Some genotypes accept been suggested as the near probable causative agents of human papillomavirus, whose carcinogenic issue in oropharynx was first proposed by Syrjänen et al.^[xv] in 1983 according to common morphological characteristics of HPV and immunohistochemistry. Later, this was confirmed by using new techniques such as "Southern Blot Hybridization".^[sixteen,17] HPV has been proposed every bit a major risk cistron for oropharyngeal squamous cell carcinoma (OPSCC),^[vii,18] with a strong association in subjects with or without the established risks of smoking and alcohol.^[vii]

The oncogenic potential of certain high-risk HPV genotypes is related to its ability of integrating DNA fragments (E5, E6 and E7) in the host prison cell, annulling the function of tumour suppressor factors such equally p21, p53 and pRb routes.^[19] However, there are many ethno-geographical differences between the examined groups, with detection ranges from 0 to 100%.^[18,20-24] Virus detection is also afflicted past the sensitivity of the diagnostic exam and the location of the lesion, which hard the clarification of the role of HPV and its carcinogenic potential.^[vii,25]

Some authors non only involve the virus in the pathogenesis of OSCC, only likewise believe that it tin determine the prognosis and module treatment response.^[26] The first type of HPV isolated in OSCC was HPV16 in the palatine tonsil, fabricated by Niedobitek et al.^[27] in 1990. However, this is non the but subtype identified, varying co-ordinate to the analysed population sample.^[28] Recently this type of HPV-positive tumours in the oral cavity was described as an entity with unlike molecular, clinical, etiological, pathological and prognostic characteristics.^{[vi,20-23,29-32]}

Methods

A review of manufactures published in the last ten years (since February 29, 2016 until January 1, 2005) in the database of medical literature MEDLINE via PubMed search engine was performed. The following descriptors obtained from "DeCS" were used equally keywords: "Papillomavirus Infections", "Carcinoma, Squamous Cell" and "Mouth". All possible associations between them were used.

The main objective was to study the office of HPV in the evolution, molecular biology, prognosis and treatment of OSCC. We also provided special attending to detection and sampling techniques, risk factors, epidemiology, human relationship with other non-cancerous lesions and history of the virus.

Inclusion criteria were: (i) studies published betwixt the dates indicated; (ii) English language; (3) both observational and experimental studies; (4) reviews and meta-analyses; and (5) items that although published at an before date than the cut-off, are cited in the main revised. Exclusion criteria were: (1) publications that do not appear in the set date range and which are non mentioned in whatsoever of the included; (2) any type of non-English language; (iii) studies lacking internal or external validity; (four) editorials and case reports; (5) studies with a sample size lower than 30, or if information technology is non mentioned by any of the included; and (half dozen) articles that do non contain information on the main search object.

Results

We preliminarily establish 252 articles, of which only 39 were included and reviewed. Among these, 9 publications were highlighted: iv meta-analysis,^[14,33-35] 3 prospective studies^[32,36,37] and ii retrospective studies.^[38,39] Chief results from these studies are summarized in Table 1.

Table 1

Nine highlighted publications

Author	Yr	Study	Objective	Number	Results
Miller and Johnstone^[33]	2001	Meta-analysis	To determine the significance of the relationship of HPV in the progressive development of oral cancer	four,680	HPV is detected with increased frequency in oral dysplastic and carcinomatous epithelium in comparison with normal oral mucosa
Kreimer et al.^[fourteen]	2005	Meta-analysis	To depict the prevalence and type distribution of HPV past anatomic cancer site	v,046	Tumor site-specific HPV prevalence was higher among studies from North America compared with Europe and Asia
Ragin and Taioli^[35]	2007	Meta-analysis	To study the overall human relationship between HPV infection and OS and DFS in HNSCC	3,151	The improved Os and DFS for HPV+ HNSCC patients is specific to the oropharynx; these tumours may have a distinct etiology from those tumours in not-oropharyngeal sites
Jayaprakash et al.^[34]	2011	Meta-analysis	To provide a prevalence estimate for HPV-16/18 in OPD	458	HPV-sixteen/18 were 3 times more common in dysplastic lesions (OR, three.29; 95% CI, 1.95- five.53%) and invasive cancers (OR, iii.43; 95% CI, 2.07-5.69%), when compared to normal biopsie
Rosenquist et al.^[32]	2007	Prospective	To evaluate the influence of unlike adventure factors for recurrence or the appearance of new second primary in the OSCC	128	High-risk HPV cases accept a higher gamble of recurrence/second primary tumours, but lower run a risk of death in intercurrent disease, compared with HPV-
Fakhry et al.^[36]	2008	Prospective	To evaluate the association betwixt tumour HPV status with the therapeutic response and survival	96	HPV+ HNSCC respond better to QT and RT-QT, with ameliorate overall survival rate at two years and reduced risk of illness progression than HPV-
Rischin et al.^[37]	2011	Prospective	To determine the prognostic significance of p16 and HPV in patients with OPC	185	HPV+ OPC is a distinct entity with a favorable prognosis (when compared with HPV-). When it is treated with cisplatin-based chemotherapy
Ang et al.^[38]	2010	Retrospective	To study the association between tumor HPV condition and survival in phase Three and 4 OPD	743	Among patients with OPC, tumor HPV status is a strong and independent prognostic factor for survival
Lassen et al.^[39]	2014	Retrospective	To test the hypothesis that the bear on of HPV/p16 as well extends to non-OP tumours	ane,294	The prognostic impact of HPV- associated p16-expression may be restricted to OPC merely

Word

There is much written literature about the relationship of HPV virus and OSCC. Due to the great disparity of published data, it is very difficult to establish rightly the role HPV plays and its etiopathological, clinical and prognostic considerations. This tin be related to differences in written report populations (genetic, social and cultural factors) and the methodology of study and detection of virus.

There are many HPV genotypes identified, within which, over 130 are related to skin and mucosal lesions.^[40] The first to propose the pathogenic human relationship of this type of virus with OSCC was Syrjänen et al.^[15] in 1983. And the commencement type identified in head and neck was HPV16 in palatine tonsil carcinomas.^[27] Since then, in that location accept been many published studies on detection and nigh its role in OSCC.

HPV molecular biology

HPV belongs to a heterogeneous group corresponding to the "Papillomaviridae" family unit.^[41] It is characterized as a DNA-double stranded virus. It has a diameter of 50 μm and it is covered past an icosahedral capsid consisting of 72 capsomeres, without casing^[42,43] and presents a particular tropism past keratinocytes, beingness the synthesis and expression of their genes linked to the level of their differentiation.^[44]

At that place are different routes of infection, mainly sexual, vertical and cocky-inoculation; they all share the need for close contact to occur.^[45,46] Manual from non-primates to humans is unknown to occur.^[47,48]

To active the infection, the virus must reach the epithelial basal layer, where the specific integrin blastoff 6 receptor is present.^[33] Once the infection becomes productive, cytopathic effects tin announced, first of all koilocytosis.^[44] To make this happen, the patient's allowed response plays an of import role. During infection, viral antigen presentation is minimal and thus the infection tin can persist until years.^[33] In immunocompetent patients lesions usually regress spontaneously, while in immunodeficient the incidence and persistence of them is commonly college.^[49]

Regarding the oncological potential of the virus, there is much controversy about the true role played by the integration of viral Deoxyribonucleic acid into human epithelial cells. Several authors take investigated its pathogenesis in OSCC. According to its part in the development of cervical cancer, HPV is classified into a high run a risk for malignant lesions subtype (HPV sixteen, 18, 31, 33, 35, 45, 51, 52, 56, 58, 59, 68, 73 and 82) and depression-grade malignant lesions subtype but related to benign lesions (HPV 6, 11, xiii, 32, 42, 43, 44).^[33,50]

The HPV genome is divided into about eight open reading frames (ORFs) divided into three regions:^[2,33] (1) early on region (E): it is required for replication, cell transformation and control of viral transcription; (2) belatedly region (Fifty): it encodes structural proteins; and (three) long control region (LCR): it is required for replication and transcription of viral Deoxyribonucleic acid.

In Due east, three proteins are encoded, which are frequently described as involved in the carcinogenesis related to the virus: pE7, pE6 and pE5.^[ii,33,44] PE5 stimulates proliferation and inhibits apoptosis, while pE7 and pE6 deed as oncogenes.^{[2,33,47,48,51,52]}

The terminal outcome is an induced and unregulated prison cell proliferation, with consequent immortality of the keratinocyte^[nineteen] due to the integration and expression of the viral genome into the host jail cell. Chromosome aberrations and excessive production of viral Dna^[53,54] all occur due to inhibition of tumor suppressor factors (p21, p53 and pRb roads).^[19]

However, although the involvement of inhibition of tumor suppressor factor p53 in the carcinogenic effect of HPV seems to exist clear, there are some publications that question the relationship of p53 polymorphism with the adventure of oral cancer,^[55] suggesting that HPV does non play an of import role oral lesions due to low detention in their analysed.^[56-59] This could exist justified by population differences, sample size, detection techniques and tumor location. Some studies suggest that in HPV+ OSCC, p53 mutation is conditioned by tumor localization and expression of E6 and E7 viral genes, appearing a mutated p53 when the tumor is HPV+ but it does not express these genes (mainly oropharynx), or when the tumor is HPV-.^[sixty,61]

Epidemiology and prevalence

Epidemiology and prevalence of HPV infection associated with OSCC varies according to the published data. Large studies tend to have lower rates of HPV (< 50%) than smaller studies (0-100%).^[25,62] Miller and Johnstone^[33] in a meta-analysis about 4,680 patients with OSCC from 94 reports reported that HPV was present in 46.v% of the cases (95% CI, 37.half-dozen-55.5%). Even so, the oral cavity was not the most often location, being surpassed by the oropharynx.^[63,64]

Kreimer et al.^[14] in a meta-analysis from 60 publications in 2005 (5,046 patients) reported that the overall prevalence of HPV in OSCC was 25.9% to 34.5%.^[14,25] The prevalence of OSCC ranges from < 2% to 100%^{[10,25,57,65]} and it may exist considering some studies practise not differentiate betwixt Parafine Embedded and Fresh Frozen biopsies or dissimilar classification criteria, including incorrectly OPSCC within the OSCC, making an overestimation.^[25]

There is an association between the presence of HPV and historic period; patients older than 60 years take a lower HPV+ prevalence (29.four%) compared to patients under that age (77.eight%).^[66] Within the OPSCC HPV+, HPV16 is higher in patients younger than fifty years.^[67,68] In relationship to sexual behaviour, the risk of oral cancer increases in male patients with decreasing historic period of commencement intercourse, with increasing numbers of partners and history of genital warts.^[69]

Regarding to etnogeographical differences, some authors suggest that Japanese studies tend to have the highest rate of HPV,^[70,71] while Africans tend to take the lowest charge per unit.^[59] Kreimer et al.^[14] established that HPV+ prevalence was higher amongst studies from North America compared with those from Europe and Asia. In 2016, Mehanna et al.^[72] conducted a prospective study of 801 patients with head and neck cancers. They established the geographic variability (differences betwixt continents) as an independent adventure factor for HPV+ prevalence of OPSCC. Information technology is most prevalent in Western Europe, when compared to Eastern Europe (37%, 155 of 422 vs. half-dozen%, 8 of 144; P < 0.0001) and Asia (37% vs. two%, iv of 217; P < 0.0001).

Regarding the genotype, the most prevalent is HPV16 (68.2-90%)^[xiv,33,66] [Figures 1-iii] followed by HPV18 (34.1%).^[14,73] But this varies depending on the series analysed and the techniques used, and that proportion may exist reversed, being higher HPV18.^[28,59] Although the association between HPV and OSCC is described,^{[32,62,68,74-77]} information technology is important to note that loftier-risk genotypes HPV16 accept been detected in normal oropharyngeal mucosa,^[78,79,62] questioning this causal human relationship. In 2001, Mork et al.^[80] defined HPV infection as a take a chance factor for OSCC, whose exposure may precede the occurrence of OPSCC in 10 years and older.

Figure one. The case of a lxx-year-old and ex-smoker female patient with a human papillomavirus+ head and neck squamous cell carcinoma. Nosotros can encounter an exophytic lesion three years of evolution on the left floor of the mouth, surpassing the midline, with a progressive growth. The patient has no dysphagia or dyspnea. We decide to take biopsies, obtaining the diagnosis of squamous cell carcinoma

Figure 2. Positron emission tomography-computed tomography shows a mass in the left region of the anterior oral cavity floor, with marked increase glucose metabolism, most iii cm in diameter and high probability of malignancy. The other cervical structures have normal glucose metabolism, showing no other hypermetabolic neoplastic interest

Figure 3. Intraoperative image. Subsequently performing tracheotomy, double functional bilateral cervix dissection, excision of the lesion with macroscopic margins higher up the centimeter and subsequent reconstruction with radial forearm flap was performed. Histological results reveals a pT3N0M0 human being papillomavirus 16+ squamous jail cell carcinoma, with shut resection margins, 6 mm thickness, with no vascular or perineural infiltration. After surgery, the patient received adjuvant radiotherapy. She is currently without signs of loco-regional recurrence

In the oropharynx in that location is no hard show linking HPV with alcohol or tobacco use, and the absence of synergism is the most accepted hypothesis,^[81] suggesting ii means for the development of OPSCC, one derived from smoking with or without alcohol and another derived from the HPV inducted genomic instability.^[31]

Most frequent location

HPV has a predilection for the oropharynx and the Waldeyer ring.^[xiv,24,59] It is estimated that the almost frequent location for detecting papillomavirus Dna is the palatine tonsil and the base of the tongue, with a strong causal association,^[14,82] independently of the influence of smoking or alcohol. Oropharyngeal HPV+ tumours appears in up to six times more often than in other tumours of the head and neck.^[six] Snijders et al.^[83] were the first to suggest the amygdala is linked with the HPV, in 1992.

Detection, diagnosis and typing techniques

Molecular assays are the gold standard for HPV identification,^[84] mainly polymerase chain reaction (PCR),^[85] specifically the reverse transcription PCR (RT-PCR) to measure viral mRNA E6 and E7 in fresh tissue.^[86] It has a high sensitivity.^[lxxx,85-88] It is fifty-fifty able to observe latent infections. Other tests that have been used for detection of HPV are "Southern Blot" (less sensitivity than PCR)^[89] and in situ hybridization (ISH) (less sensitive and less expensive than PCR). Some authors accept proposed the combination of PCR with ISH, combining the advantages of the two tests: the high sensitivity of PCR and the ability of ISH to place and localize genomic sequences linked to HPV in this kind of tumours.^[90,91]

P16 is a poly peptide used by some authors as a biomarker for HPV infection, which can exist expressed when viral Deoxyribonucleic acid is integrated into the host cell. Information technology reflects the functional effects derived from the inactivation of pRb, induced by E7. It is detected by immunohistochemistry staining and it tin be used as a predictor of HPV infection in OPSCC, even being proposed by some authors the detection of p16INK4A equally an initial test, followed past the detection of HPV in which are positive for this.^[92-94]

Regarding to the sample being sent for testing, the most usually accustomed information technology is taking biopsies or tumour specimen analysis [Figure i]. This allows non only molecular analysis but as well morphological analysis of the piece, including all jail cell layers where the virus may be latently.^[95] As a method of screening for epidemiological studies, Lawton et al.^[96] reported that mouthwash is the technique of pick, although college performance past combining different sampling techniques is obtained.

Virus relationship with other oral lesions

Since the early 1980s some authors accept reported the presence of HPV not only in cancerous lesions of the oral cavity, but likewise in premalignant lesions.^[15,97,98] Recently, the presence of HPV has been identified as an independent prognostic gene for survival in patients with OPSCC.^[38] Miller and Johnstone^[33] indicate that HPV (depression and high risk serotypes) are ii-3 times more detected in precancerous mucosa and almost 5 times more detected in carcinoma than in non-neoplastic mucosa: (i) 22.2% in benign leukoplakia; (2) 26.ii% in intraepithelial neoplasias; and (3) 46.5% in OSCC, with a detection probability of high-risk ones 2.8 times higher than depression gamble.

Jayaprakash et al.^[34] published in 2011 a meta-assay about 458 oropharyngeal dysplasias, estimating that the prevalence of HPV16/18 is 24.5%. They reported that HPV16/18 were three times more common in dysplastic lesions (OR, 3.29; 95% CI, 1.95-5.53%) and invasive cancers (OR, 3.43; 95% CI, 2.07-5.69%), when compared to normal biopsies. In addition, they found these two genotypes are at least two.5 times more common in men than in women. Within oral leukoplakia, proliferative verrucous leukoplakia is believed to accept a stronger relationship with HPV^[44] mainly 16, with a range of onset between 10% and 85%,^[99,100] and higher rate of cancerous transformation.^[101] Some authors have likewise reported a human relationship between lichen planus and HPV, ranging from 0 to 100%,^[102] which indicates the existing controversy well-nigh this association.

Many publications are studying virus connection with benign lesions or even in normal mucosa, varying its prevalence depending on the technique used, many times no PCR techniques are used, which may underestimate measurements. As a summary:

Advent in normal mucosa: varies between 0 and 81%.^[78,103] It may appear subclinical or latent,^[104] being detected past the extreme sensitivity of the PCR and may be or non related to the emergence of a future lesion.

Squamous papilloma: clinically ofttimes duplicate from common warts. HPV genotypes half-dozen and xi are most ofttimes associated, detected past ISH.^[105]

Condyloma accuminatum: it is a sexually transmitted infection and it is usually related to HPV half dozen and 11 infection, varying its positivity between 75% and 85% in oral lesions.^[106,107] Furthermore information technology is too related to the HPV 16.^[108,109] Information technology is usually present in HIV+ patients.^[110]

Common wart (verruca vulgaris): oral lesions commonly upshot from autoinoculation from the fingers. It usually occurs in children. The HPV two is described equally the most frequently related, followed by HPV 57,^[106,111] detected most of the time with no PCR techniques betwixt 80% and xc%. Other authors with more recent publications detected more than frequently HPV2 and 4.^[109]

Focal epithelial hyperplasia (Heck's disease): they usually occur in children and young adults. There is usually genetic predisposition.^[112] HPV13 (20%) and HPV32 (60%) are related to those lesions.^[113-115]

Prognosis and treatment

There is much controversy almost the office that infection past the HPV plays in the prognosis and treatment of patients with OSCC. Most of the published studies are retrospective. But they do more often than not conclude that the presence of HPV divides these tumours in two different entities with dissimilar prognostic and therapeutic implications. The most normally accepted is that patients with OPSCC HPV+ have a better prognosis due to increased survival, showing better treatment response rates.^{[36,38,63,116-118]}

The most cited paper in the literature is the one published past Fakhry et al.^[36] in 2008. They conducted a prospective phase 2 study of 96 patients with oral, oropharyngeal and laryngeal SCC. All patients received 2 cycles of induction chemotherapy with paclitaxel and carboplatin followed by concurrent weekly paclitaxel and radiotherapy. They detected HPV (types 16, 33 and 35) with PCR and ISH in forty% of all patients. They compared their response to treatment with HPV-: OSCC HPV+ have amend respond to chemotherapy (82% vs. 55%, difference = 27%, 95% CI, ix.iii-44.7%; P = 0.01) and chemo-radiotherapy (84% vs. 57%, difference = 27%, 95% CI, ix.7- 44.iii%; P = 0.007).

Patients with OSCC HPV + have a better overall survival charge per unit at two years [95% (95% CI, 87-100%) vs. 62% (95% CI, 49-74%), (difference = 33%, 95% CI, 18.6- 47.four%; P = 0.005, log-rank test)] and a lower risk of disease progression than HPV- [Hazard Ratio (HR), 0.27; 95% CI, 0.x-0.75%].

In 2007, Ragin and Taioli^[35] performed a meta-analysis of 37 studies, which conclude that patients with OSCC HPV+ had a lower take a chance of death (HR = 0.85 target; 95% CI, 0.7-one.0) and lower risk of recurrence (Hr = 0.62% target; 95% CI, 0.5-0.viii) than in HPV-. Regarding OPSCC they conclude that HPV+ had a reduced adventure of death of 28% (Target HR 0.72; 95% CI, 0.5-1.0) compared with HPV- with a similar effect for affliction-free survival (Meta Hour, 0.51; 95% CI, 0.4-0.7).

In the same year, Rosenquist et al.^[32] conducted a prospective report of cases and controls over 128 Swedish patients with OPSCC to evaluate the influence of unlike risk factors for recurrence or appearance of new second primaries in the first 3 years later the diagnosis. They establish, dissimilar other published studies that high-gamble HPV+ cases had a college risk of recurrence/second master neoplasm, but lower risk of death in intercurrent disease, compared with HPV- ones.

In 2008, Worden et al.^[119] conducted a study about the response to treatment of 66 patients with OPSCC. They plant that the presence of HPV was significantly associated with response to chemotherapy (P = 0.001), chemo-radiotherapy (P = 0.005), with better overall survival (P = 0.007) and disease-gratuitous survival (P = 0.008). They conclude that chemotherapy followed by chemo-radiations therapy is an effective handling especially in patients with HPV + OPSCC.

In 2010, Ang et al.^[38] conducted a retrospective study of the association betwixt tumor HPV status and survival amidst 743 patients with phase III or 4 OPSCC who were enrolled in a randomized trial comparing treatment with accelerated-fractionation RT+ cisplatin vs. standard-fractionation RT+ cisplatin. Amongst 323 OPSCC, 63.8% were HPV+, which presented better three-year rates of overall survival (82.iv% vs. 57.1% amid patients with HPV- negative tumours; P < 0.001 by the log-rank test) and they also had a 58% reduction in the risk of death (60 minutes, 0.42; 95% CI, 0.27 to 0.66). They concluded that among patients with OPSCC, tumor HPV status is a stiff and independent prognostic factor for survival.

Some authors accept studied the prognostic influence of some biomarkers related to HPV infection in OSCC. I of the most studied biomarkers is p16, being observed that p16+ and HPV+ patients have a better overall survival compared with HPV- or HPV+ simply p16-.^[93] This was corroborated in the prospective stage Three study of concomitant chemotherapy published in 2011 by Rischin et al.^[37] In a sample of 465 patients with OPSCC stage 3 or 4, 172 were analysed with evaluable HPV and p^16INK4A condition, and 185 with eligible p16 status. They randomized RT+ cisplatin with or without tirapazamine, concomitantly. They establish that p16+ tumours compared to p16- presented: (1) higher rates of overall survival at 2 years (91% vs. 74%; HR, 0.36; 95% CI, 0.17-0.74; P = 0.004); (2) higher rates of relapse-free survival (87% vs. 72%; HR, 0.39; 95% CI, 0.xx-0.74; P = 0.003); and (three) lower loco-regional recurrence and death rates from other causes. They besides observed a tendency in favour of tirapazamine grouping in terms of improved loco-regional control affliction in p16- patients (Hour, 0.33; 95% CI, 0.09-1.24; P = 0.13). They concluded that OPSCC HPV+ take a favourable prognosis when treated with cisplatin-based chemotherapy, compared to HPV-.

In 2014, Lassen et al.^[39] published a retrospective report among 1,294 Danish patients with advanced stage OPSCC. They observed that p16 positivity was significantly higher in oropharyngeal than not-oropharyngeal SCC (P < 0.0001). OPSCC p16+ presented a statistically pregnant improvement in loco-regional affliction control with chief RT [HR (95% CI), 0.38 (0.29-0.49)], complimentary survival events [60 minutes (95% CI), 0.44 (0.35-0.56)] and overall survival [60 minutes (95% CI), 0.38 (0.29-0.49)], unlike in non-OP.

Future therapeutic lines

HPV+ OSCC response to RT, chemotherapy and the combination of both are topics widely approached in the literature and specialized forums. However, little or zero is known about immunotherapy techniques and their effectiveness. In 2015, Rosenthal et al.^[120] published a retrospective assessment of the IMCL-9815 study, trying to find if there were whatever differences in treatment patients with RT alone vs. RT+ cetuximab, in a serial of 182 OSCC patients, in relation to the presence or absence of HPV and p16. They concluded that the improver of cetuximab to RT improved clinical outcomes regardless of p16 or HPV positivity. They also indicated that p16 does not predicted response to cetuximab.

Dissimilar cervical cancer, regarding OSCC at that place is not much literature on the use of HPV vaccines to treat these tumours. The effectiveness of the HPV vaccine against OSCC is not yet proven.

In determination, there is much controversy nigh the carcinogenic potential of HPV. Its mechanism usually involves the pE7 and pE6 proteins, which tin can delete p53, p21 and pRb routes.

HPV+ patients are ordinarily diagnosed at a younger age, mainly those with oropharyngeal tumours, presenting positivity starting time of all for HPV16 > HPV18, although information technology varies depending on the population and the exam used to notice the infection.

For more diagnostic performance, the most advisable is to use the combination of several techniques. P16 positivity needs to be mentioned in special attending as a predictor of HPV infection in the OPSCC for their prognostic and therapeutic considerations.

HPV tin announced in normal mucosa, benign and precancerous lesions.

The most commonly accustomed is that the presence of HPV divides OSCC, mainly oropharyngeal, in ii types of tumours with different prognostic and therapeutic implications.

Despite the slap-up controversy in prognosis, near studies tend to indicate that HPV+ OSCC have an increased survival, ameliorate treatment response rates, lower chance of death and lower chance of recurrence [Effigy 3].

The oropharyngeal region should exist analysed separately. OPSCC HPV+ tend to answer better to radio-chemotherapy treatments, considering the HPV positivity as a strong and independent survival prognostic cistron. In addition, if p16+, these tumours tend to have better survival and loco-regional illness-control.

Future enquiry should evaluate the possibility of new treatments.

Financial back up and sponsorship

Nil.

Conflicts of interest

In that location are no conflicts of interest.

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Ramírez-Pérez FA. The role of homo papillomavirus in oral squamous cell carcinoma. Plast Aesthet Res 2016;3:132-41. http://dx.doi.org/ten.20517/2347-9264.2016.17

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Source: https://parjournal.net/article/view/1381#:~:text=Conclusion%3A%20HPV%20divides%20OSCC%20in,risk%20of%20death%20and%20recurrences.

The Role of Human Papillomavirus in Oral Squamous Cell Carcinoma (Review)