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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 3  |  Page : 619-623

Head and neck squamous cell carcinoma in HIV, HBV and HCV seropositive patients - Prognosis and its predictors


1 Department of Head and Neck Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
2 Department of Medical Gastroenterology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
3 Department of Medicine, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
4 Department of Radiation Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India

Date of Submission10-Mar-2019
Date of Decision06-Oct-2019
Date of Acceptance20-Oct-2019
Date of Web Publication09-Jun-2020

Correspondence Address:
Shivakumar Thiagarajan
Department of Head and Neck Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_166_19

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 > Abstract 


Introduction: Patients receiving treatment for head-and-neck squamous cell carcinoma (HNSCC) also may have coexisting viral infections caused by HIV, HBV, and HCV (seropositive). There is scarce literature regarding the clinical presentation and treatment outcomes for these patients with coexisting viral infections (seropositive HNSCC). We conducted this study to assess the clinical presentation and treatment outcomes (overall survival [OS] and disease-specific survival [DSS]) of seropositive HNSCC patients.
Methodology: This was a retrospective cohort study on seropositive HNSCC patients registered at our center from 2012 to 2014. The viral infections were identified by the presence of the antibodies to these viruses in the patient's blood samples.
Results: Out of the 19,137 HNSCC patients registered, 156 patients had HBV, HCV, and/or HIV infection. Among these, HBV infection was the most common (n = 86/156, 55.1%) followed by HIV infection (n = 36/156, 23.1%) and HCV infection (n = 29/156, 18.6%). The oral cavity was the most common subsite involved. Majority of these patients presented at an advanced stage (advanced T stage – 71.8% and node positive – 62.2%). The majority of the patients received curative-intent treatment (65.4%). The OS at 3 years for these HNSCC patients with coexisting HIV, HBV, and HCV infection was 60%, 62.6%, and 57.5%, respectively, and their DSS at 3 years was 58.8%, 78.6%, and 53.8%, respectively.
Conclusions: Seropositive patients with HNSCC often present in the advanced stage but have a good survival if treated appropriately.

Keywords: HBV, HCV, head-and-neck cancers, HIV, seropositive, squamous cell carcinoma


How to cite this article:
Nayyar SS, Thiagarajan S, Malik A, D'Cruz A, Chaukar D, Patil P, Alahari AD, Lashkar SG, Prabhash K. Head and neck squamous cell carcinoma in HIV, HBV and HCV seropositive patients - Prognosis and its predictors. J Can Res Ther 2020;16:619-23

How to cite this URL:
Nayyar SS, Thiagarajan S, Malik A, D'Cruz A, Chaukar D, Patil P, Alahari AD, Lashkar SG, Prabhash K. Head and neck squamous cell carcinoma in HIV, HBV and HCV seropositive patients - Prognosis and its predictors. J Can Res Ther [serial online] 2020 [cited 2020 Aug 7];16:619-23. Available from: http://www.cancerjournal.net/text.asp?2020/16/3/619/286251




 > Introduction Top


Head-and-neck squamous cell carcinoma (HNSCC) is the sixth common cancer worldwide.[1],[2] These cancers are commonly associated with tobacco (smoked and smokeless) and alcohol abuse.[3] Viral infections have also been implicated in the causation of HNSCC.[4] For example, there is a known association of HPV infection with oropharyngeal carcinoma[4] and EBV infection with nasopharyngeal carcinoma.[5] Association of HNSCC with HCV has been assessed in a few studies.[6] Su et al. observed that patients with HCV infection have a higher risk of developing oral cancer.[6] It is observed that patients with HNSCC sometimes have associated HIV, HBV, and HCV infections (seropositive), either alone or in combination. There is a scarcity of literature regarding the treatment response and the prognosis of these patients. The treatment of these viral infections, in general, has improved over the years and so has their survival.[7],[8],[9]

With the introduction of effective highly active antiretroviral therapy, a larger number of patients with HIV are surviving for a longer time and they often present with various non-AIDS-defining cancers.[7],[10] Prevalence of hepatitis B in Southeast Asia has been found to be up to 2.7%.[11] These patients often have compromised liver function with cirrhosis and eventually may develop liver cancer.[12] Patients with hepatitis C may have a similar complicated course. However, the availability of newer oral drugs has revolutionized the treatment of HCV infection in recent years with improved tolerance and response rates. As there is limited literature available on the clinical presentation, treatment outcomes and the prognosis of seropositive patients with HNSCC, we conducted this study to assess the demographic profile, clinicopathological presentation, and oncologic outcomes of the seropositive HNSCC patients. Approval was obtained from the Institution Review Board for this study and registration with the Central Trial Registry of India was done (CTRI/2018/04/012911).


 > Methodology Top


This was a retrospective cohort study conducted at a tertiary care cancer center. We screened the electronic medical records of all the patients of HNSCC registered at our center between 2012 and 2014 with coexisting viral infections (HIV, HBV, and HCV). Treatment-naïve patients with HNSCC, above 18 years of age, with one or more coexisting viral infections (HIV, HBV, and HCV), registered in our hospital for treatment, were included in the study. Those with second primary/recurrence were excluded. The demographic profiles, addictions, stage of the disease, site, intent of the treatment, treatment modality, survival, and the disease status were recorded from the electronic medical records. Those patients whose follow-up details were not available on the electronic medical records were contacted telephonically. The primary objective was to determine overall survival (OS) and disease-specific survival (DSS) among seropositive HNSCC patients. The secondary objective was to evaluate the clinical presentations and patterns of care given to these patients. SPSS Version 24.0 (IBM, NY, USA) was used for statistical analysis. DSS and recurrence-free survival were calculated using the Kaplan–Meier analysis. Chi-square test was used to assess the association between different factors. P <0.05 was considered statistically significant.


 > Results Top


There were 19,137 patients registered between 2012 and 2014 with head-and-neck cancer. Of these, 271 patients had one or more coexisting viral infections with HIV, HBV, and HCV. The viral infections were identified by the presence of the antibodies to these viruses in the patient's blood samples. The seropositivity rate in this cohort was 1.42%. Among the 271 patients, HNSCC was present in 156 patients. These 156 patients were included in the study as they satisfied the eligibility criteria.

The age of the patients ranged between 25 and 82 years [Table 1]. The median age was 57 years. The majority were male (84.6%). All patients, except one, had an ECOG performance status of ≤0–2. The oral cavity was the most common site (65.4%) followed by the larynx (14.1%), hypopharynx (10.3%), oropharynx (9.6%), and nasopharynx (0.6%). The majority of the tumors had advanced T-stage (71.8%) and had nodal positivity (62.2%) and a small proportion of patients (4.5%) had distant metastasis at presentation. All patients used either tobacco (89.7%) or areca nut (9.6%). Only one patient in our cohort (0.7%) had no addictions at all. Comorbidities were present in only 23.7% of patients [Table 1].
Table 1: Clinical and demographics details

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HNSCC patients with HBV infection was the most common association (n = 86/156, 55.1%) [Figure 1], followed by HIV infection (n = 36/156, 23.1%) and HCV infection (n = 29/156, 18.6%). A small percentage of patients (1.9%) had both HIV + HCV infection and HBV + HCV infection (1.3%). There were no patients having all the three infections or a combination of HIV infection and HBV infection. Three patients with HBV/HCV infection (n = 3/120, 2.5%) had cirrhosis; two patients out of the three had portal hypertension in addition.
Figure 1: Pie chart depicting the distribution of HIV, HBV, and HCV in head-and-neck squamous cell carcinoma in the study

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Treatment

These patients received treatment as per the standard of care for the particular site and stage of disease with which they presented. The majority of the patients were treated with curative intent (65.4%). Among them, 76 underwent surgery, 4 received radical radiotherapy, 22 received chemoradiation (CCRT), and treatment details of 6 were not known. The remaining 34.6% of patients were treated with palliative intent due to the advanced nature of the disease. Among these, 25 patients received palliative chemoradiation, 9 received palliative chemotherapy, and 20 received palliative radiotherapy.

Survival analysis

Overall, the OS at 3 years for HNSCC patients (for all sites, stages, and inclusive of both radical and palliative intent treatment) with HIV, HBV, and HCV infection was 60%, 62.6%, and 57.5%, respectively, and their DSS was 58.8%, 78.6%, and 53.8%, respectively. The OS and DSS as per the treatment intent, subsite, and stage (early vs. advanced) are given in [Table 2].
Table 2: Overall and disease-specific survival of seropositive head and neck squamous cell carcinoma (all values are in percentages at 3 years)

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 > Discussion Top


The HNSCC are among the most common cancers in Southeast Asia.[13] It has been observed that this geographic area also has a sizable population with viral diseases caused by HIV, HBV, and HCV. The prevalence of HIV infection is third highest among the different regions in the world.[14],[15] Hepatitis B has a prevalence of up to 2.7% in Southeast Asia.[11] HCV has also been found to have a prevalence of 1.85% among the blood donors.[16] With so many patients living with these diseases and surviving longer than earlier due to better treatment for these infections,[9] we are getting to see more patients of HNSCC coexisting with these diseases.

In a large western study comprising of patients from the NCDB database, 10265 HIV patients were compared with 2 million HIV-negative patients,[17] and it was found that HIV-positive patients with low CD4 counts, male gender, and patients in the age between 45 and 64 years had poor prognosis and had a lesser chance of getting treated in cases of DLBCL, cervical, lung, and anal cancers. However, this study included patients with all types of cancers and was not specific for head-and-neck cancers. The head-and-neck cancer patients with HIV infection constituted 4.9% (502 patients) of all the HIV-positive patients. Similar results were reported by an Italian study after excluding AIDS-related malignancy.[18]

In a study of 539 patients from Southeast Asia with upper aerodigestive tract SCC, HIV positivity rate of 4.5% was observed.[19] The reported survival was significantly poorer in patients with HIV infection (P = 0.01). Silverberg et al. did a study on the risk of cancers in patients with HIV infection,[20] it was found that infectious cancers are more common than noninfectious cancer among HIV patients (the relative risk for infection-related non-AIDS-defining cancers was 9.2 [95% confidence interval (CI): 7.7–11.1]). Epstein et al. reported in their article that among HIV-seropositive patients, the most common oral cancers are Kaposi's sarcoma and non-Hodgkin's lymphoma.[21] Grulich et al.[22] in their meta-analysis on the incidence of cancer in HIV and immunosuppressed patients reported that most of the cancers found had a known infectious cause. These included all three types of AIDS-defining cancer (Kaposi sarcoma, aggressive B-cell non-Hodgkin lymphoma, and cervical cancer), all HPV-related cancers, as well as Hodgkin's lymphoma (HIV/AIDS meta-analysis standardized incidence ratio [SIR] 11.03), liver cancer (SIR 5.22), and stomach cancer (SIR 1.9). This study did not note any increased incidence of epithelial cancers. However, in another study on immunosuppressed patients with HNSCC by Manyam et al., immunocompetent patients had a much better locoregional recurrence-free survival (86.1 vs. 47.3%; P < 0.0001) and progression-free survival (71.6% vs. 38.7%; P < 0.002) at 2 years.[23] Beachler et al. observed that SIRs for both HPV-related (SIR = 3.2, 95% CI = 2.5–-3.4) and HPV-unrelated (SIR = 3.0, 95%CI = 2.5–4.1) HNSCC were significantly elevated in HIV-infected individuals compared with the general population.[24] Another study by Zhang et al. found that p16 positivity among HIV-seropositive patients was associated with improved OS; (P<.001).[25] In our study, most of the patients had advanced disease at presentation [Table 1]. Similar findings were mentioned in an earlier study on AIDS-related malignancies.[26] In the same study, it was found that HIV-infected patients are at an increased risk for non-AIDS-defining malignancies. These malignancies had aggressive behavior and more advanced disease at diagnosis, which is responsible for the poor patient outcomes. Another study observed that those patients positive for HIV had larger tumors (P = 0.004) and more advanced tumor stage (TNM classification) at presentation (P = 0.05).[19] No significant difference in tumor location was present between HIV-infected and other patients. In our study, the oral cavity was the most common site afflicted (65.4%). This may be because oral cancers are the commonest cancers in this part of the world due to the rampant usage of chewable tobacco in our population.[13] In fact, in our study, 89.7% of patients were consuming tobacco in one or the other form. Smokeless or chewable tobacco users in our study were 29.5%, smoked tobacco users were 21.2%, while those consuming both smokeless and smoked were 26.3%. Another 9.6% of patients were using areca nut, which again is known to cause oral cancer.[27] Therefore, it is more likely that increased oral cavity involvement in our cohort of patients was due to concomitant tobacco and areca nut usage, rather than seropositivity itself.

A study from Southeast Asia observed a 2 years survival of 32% and 59% for HIV-positive and HIV-negative patients, respectively.[17] In our study, we observed a DSS and OS for HIV-positive patients was 58.8% and 60%, respectively at 3 years. The maximum number of patients in our cohort had hepatitis B infection [Figure 1]. Very few studies have assessed the association of HBV infection with HNSCC. A study from Taiwan on 100,000 patients found that 12,368 had HBV infection.[15] No association between hepatitis B and HNSCC could be established. In our study, the 3 years DSS for HNSCC patients with HBV infection was 78.6%, while the OS was 62.6%. There was no statistically significant difference in the age group, stage or survival for these patients when compared within the cohort.

Nearly 1.85% of blood donors in Southeast Asia are estimated to be hepatitis C positive.[16] A large study from Taiwan focused on the association of HCV and HNSCC.[15] The study found that HCV-positive patients have more than twice the risk of developing oral carcinoma and have relatively worse outcomes. The incidence of oral cavity cancers was 2.28-fold higher among patients with HCV alone than the nonviral hepatitis group (6.15 vs. 2.69/10,000 person-years). After adjusting for sociodemographic covariates, HCV alone was significantly associated with an increased risk for oral cavity cancer (hazard ratio [HR] = 1.90). This positive association was highest among individuals in the 40–49-year age group (HR = 2.57, 95% CI = 1.21–5.46). However, there were no significant associations between HBV alone or HBV/HCV dual infections and risk for oral cavity cancer. In another study from Brazil, the overall HCV prevalence in patients with head-and-neck cancer was 7.8%, reaching 12.8% in HNSCC, and 3.4% in other head-and-neck malignant neoplasms (OHNMN).[28] There was a higher risk of developing a second primary neoplasm in HNSCC compared to OHNMN patients (20.6% versus 4.6%; P = 0.001) in the study. However, the mean survival was not different between HCV-positive and HCV-negative patients (6.0 years vs. 6.6 years, respectively, P = 0.516). Among other studies in literature, the incidence of HCV in HNSCC has a wide variation, from as low as 0.9% to as high as 21.2%.[29],[30] In our study, seropositivity for hepatitis C was 18.6%. DSS and OS at 3 years were 37.9% and 57.5%, respectively, at 3 years.

There are no studies on HNSCC patients who have a combination of two or more seropositive cases. In our study, the worst survival was seen for such patients who had a combination of seropositive diseases, though they were few in numbers. The OS was just 2.5 months for patients having a combination of HIV and HCV. For patients who had both hepatitis B surface antigen and HCV seropositivity, the mean OS was 16 months. As mentioned, due to the small numbers, it was difficult to arrive at any conclusions. However, they do tend to suggest that a combination of seropositive cases might lead to a poorer outcome and survival.

Limitations of this study are its retrospective design; unavailability of the CD4 counts in HIV and DNA level for hepatitis B and C patients. Hence, an analysis of the influence of these factors on the outcome could not be done. However, to our knowledge, this is the first of its kind study, looking at the clinical presentation and treatment outcomes among the three major seropositive diseases in HNSCC together.


 > Conclusions Top


Patients with seropositivity and HNSCC often present in an advanced stage. The majority of them have a good survival if treated with curative intent. Based on our study, the presence of seropositivity should not change the general outlook of the treating clinician toward the prognosis of such patients, as the survival remains similar to that of nonseropositive HNSCC patients.

Acknowledgments

The authors would like to thank the Medical Records Department, Tata Memorial Centre, Mumbai, and Dr. Atanu Bhattacharjee, assistant professor (Biostatistics) at the Centre for Cancer Epidemiology, Tata Memorial Centre, Navi Mumbai.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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