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Laryngoscope. Author manuscript; available in PMC 2021 May 01.
Published in final edited form as:
Laryngoscope. 2021 May ; 131(5): E1558–E1566. doi:10.1002/lary.29206.
Management of Head and Neck Cancers With or Without
Comorbid HIV Infection in Botswana
Author Manuscript
Gwendolyn J. McGinnis, MD, MS, Matthew S. Ning, MD, MPH, Memory Bvochora-Nsingo,
MD, Sebathu Chiyapo, MD, Dawn Balang, MD, Tlotlo Ralefala, MBChB, Alexander Lin, MD,
Nicola M. Zetola, MD, MPH, Surbhi Grover, MD, MPH
Department of Radiation Oncology (G.J.M., M.S.N.), MD Anderson Cancer Center, Houston,
Texas, U.S.A.; Department of Oncology (M.B.-N., S.C., D.B.), Gaborone Private Hospital,
Gaborone, Botswana; School of Medicine (T.R., N.M.Z., S.G.), University of Botswana, Gaborone,
Botswana; Princess Marina Hospital (T.R., S.G.), Gaborone, Botswana; Department of Radiation
Oncology, Perelman School of Medicine (A.L., N.M.Z., S.G.), University of Pennsylvania,
Philadelphia, Pennsylvania, U.S.A.; and the Botswana University of Pennsylvania Partnership
(S.G.), Gaborone, Botswana.
Abstract
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Objectives/Hypothesis: Head and neck cancer (HNC) is the fifth most common malignancy in
sub-Saharan Africa, a region with hyperendemic human immunodeficiency virus (HIV)-infection.
HIV patients have higher rates of HNC, yet the effect of HIV-infection on oncologic outcomes and
treatment toxicity is poorly characterized.
Study Design: Prospective observational cohort study.
Methods: HNC patients attending a government-funded oncology clinic in Botswana were
prospectively enrolled in an observational cohort registry from 2015 to 2019. Clinical
characteristics were analyzed via Cox proportional hazards and logistic regression followed by
secondary analysis by HIV-status. Overall survival (OS) was evaluated via Kaplan-Meier.
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Results: The study enrolled 149 patients with a median follow-up of 23 months. Patients
presented with advanced disease (60% with T4-primaries), received limited treatment (19%
chemotherapy, 8% surgery, 29% definitive radiation [RT]), and had delayed care (median time
from diagnosis to RT of 2.5 months). Median OS was 36.2 months. Anemia was associated with
worse survival (HR 2.74, P = .001). Grade ≥ 3 toxicity rate with RT was 30% and associated with
mucosal subsite (OR 4.04, P = .03) and BMI < 20 kg/m2 (OR 6.04, P = .012). Forty percent of
patients (n = 59) were HIV-infected; most (85%) were on antiretroviral therapy, had suppressed
viral loads (90% with ≤400 copies/mL), and had immunocompetent CD4 counts (median 400
Send correspondence to Surbhi Grover, MD, MPH, Department of Radiation Oncology, Perelman School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania. University of Pennsylvania, 3400 Civic Center Boulevard, TRC 2 W, Philadelphia, PA
19104. surbhi.grover@uphs.upenn.edu.
AL has no conflicts of interest regarding the material in this manuscript, but does report being on an advisory board for Ion Beam
applications (paid honorarium) and conducting education for Provision Healthcare (paid honorarium).
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Portions of this study will be presented in oral form at the 2020 American Society of Radiation Oncologists annual meeting (Virtual,
October 2020).
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cells/mm3). HIV-status was not associated with decreased receipt or delays of definitive RT, worse
survival, or increased toxicity.
Conclusions: Despite access to government-funded care, HNC patients in Botswana present late
and have delays in care, which likely contributes to suboptimal survival outcomes. While a
disproportionate number has comorbid HIV infection, HIV-status does not adversely affect
outcomes.
Editor’s Note:
This Manuscript was accepted for publication on October 13, 2020
Keywords
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Head and neck neoplasms; HIV-related neoplasms; Radiotherapy; Global oncology; HPV-related
malignancies
INTRODUCTION
The burden of cancer is increasing worldwide. In 2018, there were an estimated 9.6 million
cancer-related deaths, an increase of >60% since 1990.1 Already, cancer-related deaths are
disproportionately concentrated in low and middle-income countries (LMIC)1; and the
cancer burden in LMICs are estimated to double by 2040.2 Many LMIC are at the early
stages of optimizing oncologic care: cancer awareness is still limited, and access to
specialized oncologic management is scarce.3,4 As such, many patients present with
advanced-stage malignancies with limited treatment options at the time of delayed diagnosis.
5,6
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Head and neck cancer (HNC), in particular, is the fifth most common cancer in Sub-Saharan
Africa (SSA).1 In 2018, approximately 30% of the 1.5 million newly diagnosed HNC cases
worldwide occurred in LMICs.1 Comprehensive work-up of HNCs often entails fiberoptic
nasopharyngolaryngoscopy, high-quality axial diagnostic imaging (e.g. CT Neck with
contrast), and human papillomavirus (HPV) staining/testing on pathology for staging
purposes. While early-stage HNCs may be readily managed with curative intent (sometimes
via monotherapy), advanced-stage disease imparts poorer outcomes. For such patients,
definitive management entails multimodality combinations of surgery, chemotherapy, and/or
radiation therapy (RT). These aggressive courses are accompanied by significant toxicities,
warranting supportive measures such as dental care, pain management, nutrition, speech
pathology, and/or percutaneous feeding tube (PEG) placement. However, access to many of
these diagnostic, specialized oncologic, and supportive care resources remain limited in
LMICs.
The incidence of squamous cell carcinoma (SCC) of the head and neck is also increased by
two- to three-fold among human immunodeficiency virus (HIV) -positive patients7–9: a
pertinent demographic in SSA, where HIV infection remains endemic.10 Botswana, for
example, is a middle-income SSA country with a population of 2.3 million affected by one
of the most severe HIV epidemics worldwide (22.2% of the adult population [age 15+] were
living with HIV in 2019).11 Robust efforts, including universal healthcare and access to
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antiretroviral therapy (ART), have fortunately begun to decrease HIV prevalence and
mortality in Botswana.11 Yet as HIV-infected patients are now living longer, they remain
susceptible to late comorbidities, including HIV-related malignancies.12
The management of non-communicable diseases such as cancer is thus an increasingly
important medical concern.1 However, data are limited regarding the treatment of locally
advanced HNC among HIV-infected patients. The objective of this study was to
prospectively evaluate patterns of oncologic care and outcomes for HNC patients with or
without HIV infection in Botswana.
METHODS AND MATERIALS
Study Setting
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Healthcare in Botswana entails a tiered system with first entry at the primary care level
across decentralized local health posts. If cancer is suspected, patients are subsequently
referred to tertiary hospitals where oncologic diagnosis and treatment are available. Nearly
all oncologic care in Botswana is provided at 1) Princess Marina Hospital (PMH; a tertiary
public hospital in Gaborone), 2) Nyangabwe Hospital (a tertiary public hospital in
Francistown), and/or 3) Gaborone Private Hospital (GPH; a private hospital in Gaborone,
with the only RT facility in the entire country. Together, PMH and GPH provide oncologic
care for approximately 1.3 million (65%) of Botswana’s population. In terms of RT access,
the only linear accelerator in the entire country is located at GPH and treats 45 to 65 patients
daily (sometimes up to 6 days per week if necessary).13 Many of these patients are referred
from the public sector, with all citizens approved for RT (at no out-of-pocket cost) through
government subsidy.
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Patient Selection and Data Collection
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This study is an analysis of HNC patients consecutively enrolled in the Botswana
Prospective Cancer Cohort (BPCC), a prospective observational cohort of patients receiving
cancer treatment in Botswana, from February 2015 to June 2019. All biopsy proven HNC
patients presenting to an oncology clinic at PMH or GPH were approached for enrollment.
Detailed methods regarding the BPCC have been previously described.14,15 Briefly, if a
patient consented to enrollment, data were collected by a research assistant at initial
consultation, on treatment visits for those getting RT, and during follow up. Patients were all
followed up every 3 months indefinitely to determine vital status and any signs of
recurrence. Data are collected via pre-designed electronic forms and database management
tools (Research Electronic Data Capture [REDCap], hosted at the University of
Pennsylvania).16 This study was reviewed and approved by the institutional review board at
the University of Pennsylvania and by the Ministry of Health in Botswana.
At initial consultation and each follow-up, comprehensive patient data are collected and
updated, including: demographic information, distance from treatment facility, marital
status, cancer screening history and risk factors, initial presenting and currently active
symptoms, HIV history, treatment prescribed versus received, Karnofsky Performance Status
(KPS) score, and other relevant medical record data. Staging work-up is frequently limited
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by lack of fiberoptic nasopharyngolaryngoscopy, high-quality axial diagnostic imaging (e.g.
CT Neck with contrast), and/or HPV staining/testing on pathology. Dates of symptom onset,
diagnosis, and treatment initiation are recorded, with time-to-treatment defined from
pathologic diagnosis to treatment start. With respect to oncologic management,
chemotherapy cycles are recorded during weekly treatment visits, and RT summary data
(such as dose and duration) are collected at the end of treatment, with any delays or pauses
noted.
Antiretroviral Treatment
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Although the incidence of new HIV infections has decreased by 36% since 2010, the HIV
prevalence in Botswana remains the second highest in the world (at approximately 22.2% of
the adult population [age 15+] in 2019).11 The Botswana National ART program provides
ART free-of-charge to all citizens. At study inception (2015), only patients with CD4 counts
≤350 cells/μl or with World Health Organization HIV stage three or four conditions17 were
eligible for ART, with efavirenz-tenofovir disoproxil fumarate (TDF) - emtricitabine (FTC)
offered as standard first-line therapy. However, starting June 2016, all HIV-infected patients
(regardless of viral load or CD4 count) became eligible for immediate ART initiation
through a Universal Test and Treat Strategy,18 and standard first-line ART transitioned to
dolutegravir-TDF-FTC.18 As a result of these measures, in 2019, 82% of HIV-infected
patients in Botswana were on ART, and 79% had achieved viral load suppression.11 All
study participants with negative or unknown HIV-status were tested for HIV as confirmation
prior to initiation of cancer treatment. Note that in Botswana, HIV status does not directly
factor into resource allocation of oncologic care.
Oncologic Management and Limitations
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Chemo-RT with concurrent cisplatin was considered for any suitable patient deemed fit
enough to tolerate definitive therapy; yet many patients were not eligible for aggressive
treatment, given their delayed presentations with advanced disease. Common
contraindications to definitive chemo-RT included poor performance status, distant
metastases, and renal dysfunction or significant cytopenias precluding chemotherapy.
Additional limitations include a relative paucity of ancillary services (e.g. dental care, pain
management, registered dieticians, speech pathology) and supportive therapies (e.g. PEGtube placement for enteral feeding) helpful for managing severe treatment-related
complications. After consideration of these factors, many patients were ultimately
dispositioned to palliative therapy. All treatment plans were subject to peer-review and
discussion among the center providers (in the absence of a robust HNC-specialized
multidisciplinary forum).
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With respect to RT, all patients underwent CT-Simulation for planning purposes, and
treatments were delivered via 3D-conformal radiation technique after volumetric target
delineation on a VERSA-HD linear accelerator (Elekta, Stockholm, Sweden). During the
period of the study, one–two radiation oncologists and one physicist were available at GPH.
Following physician contours, plans were developed by dosimetry on Monaco software
(Elekta, Stockholm, Sweden), with normal tissue constraints and target parameters
accounted for in the dose volume histogram. All plans underwent physics quality assurance
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prior to treatment delivery. Regarding prescriptions, definitive cases were conventionally
fractionated (e.g. 2 Gy per fraction) to a median cumulative dose of 70 Gy in 35 daily
treatments. These courses started with larger fields for elective coverage of regional nodal
basins (to an initial dose of 50 Gy in 25 fractions), followed by a sequential cone-down (for
another 20 Gy in 10 fractions) to the high-risk clinical treatment volume (which also
encompassed all gross disease). In contrast, non-definitive cases received a median dose of
37.5 Gy (IQR: 35–45) in 15 daily fractions (IQR: 14–20) without sequential boost. For
palliative cases, hypo-fractionated regimens (≥ 2.5 Gy per fraction) - such as 30 Gy in 10
fractions, 20 Gy in 5 fractions, 16 Gy in 4 fractions (BID), and 6 Gy in 1 fraction - were
commonly utilized.
Outcomes and Statistical Analysis
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Patient demographic and clinical characteristics were also compared within the following
patient sub-groups: 1) HIV-infected versus HIV-uninfected patients; and 2) patients who did
versus did not receive definitive doses of RT, defined here in this study as an equivalent dose
in 2-Gy fractions (EQD2) of ≥60 Gy, assuming an α/β ratio of 10. Continuous variables
were compared with the Mann-Whitney test, while categorical variables were compared via
χ2 tests, as appropriate. All statistical analyses were performed with SPSS Version 24 (IBM
Corp, Armonk, NY). For all analyses, the threshold for statistical significance was P < .05.
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Actuarial rates of overall survival (OS) were calculated via Kaplan-Meier method, computed
from the date of pathologic diagnosis, with patients censored at last contact or healthcare
facility visit. Log-rank tests were used to evaluate potential differences between groups. To
minimize follow-up loss, vital status was confirmed through verifying medical records or
contacting next-of-kin via phone, for selected cases. Patient and treatment factors were
assessed for associations with OS via Cox proportional hazards modeling, with hazard ratios
(HRs) calculated for univariate and multivariable analyses.
Acute (<3 months from RT) and late (≥3 months from RT) toxicities were prospectively
assessed and graded according to the Common Terminology Criteria for Adverse Events
(CTCAE), version 4.0. Documented events specific to HNC included: xerostomia,
odynophagia, dysphagia, fatigue, weight loss, pain, and dermatitis. Logistic regression
analysis was employed to identify potential associations between clinical or treatment
variables and toxicity events, with odds ratios (ORs) and 95% confidence intervals (CIs)
calculated.
RESULTS
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Patient and Disease Characteristics
A total of 149 pathologically confirmed HNC patients were identified, with a median
follow-up time of 23 months (Table I). All patients were citizens of Botswana currently
residing within the country. The median distance of patient resident district or sub district to
treating facility was 197 kilometers (IQR: 67–441 kilometers). Median age was 53 years
(interquartile range [IQR]: 42–61), and 60% of patients were male. Most patients (74%)
denied active tobacco-use. Roughly half (53%) had good or excellent performance status
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(KPS 90–100), yet 46% were anemic (Hgb < 12 g/dL) and 57% had low body mass index
(BMI) (<20 kg/m2) at presentation. Many patients were also symptomatic with either pain
(50%) or bleeding (17%).
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By anatomic subsite, these HNC cases included 55 oral cavity, 14 laryngeal, 14 salivary, 13
oropharyngeal, 13 nasopharyngeal, 13 orbital, 9 skin, 7 sinonasal, 7 unknown primaries
(presenting with nodal disease of the neck), and four thyroid malignancies. Orbital tumors
included pre-orbital, conjunctival, and/or eyelid tumors. Squamous cell carcinoma was the
histology among 72% of cases. All orbital tumors with known histology were SCCs. Among
the subset of patients for whom staging data were available (n = 68), 41 (60%) presented
with T4 disease (per American Joint Committee on Cancer [AJCC] 7th Edition). While axial
diagnostic imaging (e.g. CT Neck with contrast) was not available for many patients, 37%
presented with clinically apparent nodal disease; however, chest X-rays were available to
assess lung involvement, with only one patient noted to have metastatic disease.
Treatment Characteristics and Delays
Most patients failed to receive evidence-supported curative management. Only 8%
underwent surgical resection for the following subsites: salivary gland (n = 5), oral cavity (n
= 3), thyroid (n = 3), and orbit (n = 2). While 101 patients received RT (including one postop case), 58 (39%) were treated with non-definitive doses (EQD2 < 60 Gy) versus 43 (29%)
treated definitively– with only 28 (65%) of the latter prescribed ≥70 Gy. Furthermore,
definitive RT was associated with extended treatment durations (median course length: 57
days [IQR: 46–62]), with 58% treated over >8 calendar weeks; as well as significant
treatment delays (median time from diagnosis-to-RT: 2.5 months [IQR: 1.6–5.4]), with 42%
delayed ≥3 months.
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Nineteen percent of patients received chemotherapy as part of their treatment (all concurrent
with RT) for the following subsites: oral cavity (n = 13), nasopharynx (n = 7), larynx (n = 4),
oropharynx (n = 3), salivary gland (n = 1), and orbit (n = 1). Patients receiving definitive RT
were also more likely to receive chemotherapy as part of their treatment, versus those not
receiving definitive RT doses (49% vs. 7.5%; P < .001). While treatments were analyzed by
what was actually received, 13 patients did not fully complete their intended treatment
course due to toxicity limitations: nine did not finish their prescribed RT fractions, and six
missed one or more courses of chemotherapy.
Patient and Treatment Characteristics by HIV Status
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Of the 149 study patients, 59 (40%) were HIV-infected (Table II); most of whom were on
ART (85%) and had suppressed viral loads (90% with ≤400 copies/mL). The median CD4
count was 400 cells/mm3 (IQR: 237–584). Most clinical factors were similar among HIVinfected and non-infected patients (Table II). However, anatomic subsite distributions varied
by HIV status: as compared to their HIV-negative counterparts, the HIV-positive patients had
a higher proportion of orbital tumors (17% vs. 3%), but were less likely to present with
oropharyngeal (3% vs. 13%) and nasopharyngeal (3% vs. 12%) primaries (P = .012). HIV
status did not impact receipt of therapy (surgery, chemotherapy, or RT) or time-to-initiation
of definitive RT (P = .440).
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Radiation Toxicity
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Among the 101 patients treated with RT, the rates of acute grade ≥ 2, acute grade ≥ 3, and
any late toxicities were 44%, 30%, and 11%, respectively (Table III). Grade ≥ 3 toxicities
were associated with mucosal subsite (OR 4.04, P = .03) and lower BMI (<20 kg/m2) [OR
6.04, P = .012]; and lower RT dose (EQD2 < 60 Gy) was associated with decreased
likelihood of acute grade ≥ 2 events (OR 0.35, P = .012). Notably, toxicities were not found
to be associated with HIV-status, anemia (Hgb < 12 g/dL), higher KPS (90–100), low body
weight (<50 kg), or receipt of chemotherapy among this study population. Acute grade ≥ 2
and acute grade ≥ 3 were significantly lower in more recently treated patients (OR 0.20, P
< .001 and OR 0.12, P < .001).
OS
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The median OS for the entire study cohort was 36.2 months (95% CI: 20.6 – 51.8), with a 2year OS rate of 58% (Fig. 1). On multivariable analysis, anemia (Hgb < 12 g/dL) was
associated with worse survival on multivariable analysis (HR 2.74, P = .001). Notably, HIV
status was not demonstrated to be associated with OS (Fig. 2), with no appreciable
difference noted between HIV-infected versus HIV-uninfected patients (3-year OS: 51.8%
vs. 51.2%, P = .606).
DISCUSSION
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HNCs are one of the most common malignancies worldwide, associated with 650,000 new
diagnoses and 330,000 deaths per year, with 30% of newly diagnosed cases occurring in
LMICs1,19–26; however, there is a paucity of data regarding the management and outcomes
of HNCs within these settings.27 Furthermore, data are limited regarding the treatment of
HNC specifically among HIV-infected patients, who comprise a growing demographic
among cancer patients in the modern era of ART. Simultaneously addressing these literature
voids, our study is the first prospective evaluation of treatment patterns and survival
outcomes for HNC patients within: 1) a resource-limited SSA country, and 2) a population
with high HIV-burden, providing novel insights for both uncharacterized scenarios.
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One of the most important prognostic factors in HNC treatment is clinical stage at
presentation, which directs evidence-based stage-specific oncologic management.
Unfortunately, comprehensive staging work-up, including HPV status, was not available for
most study patients. Within the minority of patients (46%) for whom staging data were
available, 60% presented with advanced disease (T4 primaries). The late presentations of
this study population are also supported by high proportions of anemic (57%), underweight
(57%), and actively symptomatic (50%) patients. Their comorbidities and poor performance
statuses preclude aggressive curative treatment, particularly without access to ancillary
services to address disease- and treatment-related complications (e.g. percutaneous
endoscopic gastrostomy, enteral feeding, nutritional support, speech pathology, and
tracheostomy).
Unfortunately, these data are concordant with prior reports indicating that 54% of all cancer
patients in Botswana present with advanced-stage disease,3 despite the fact that 90% of the
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population has ready access to government-sponsored healthcare.28 This does not account
for the estimated 45% of patients in Botswana who receive no cancer-directed therapy.29
Barriers to timely oncologic care in Botswana have been previously described,6,30 including
limited cancer awareness, lack of diagnostic urgency, logistical hurdles to specialty care
access, physical distance to specialized care facilities, schedule uncertainty, and limited
provider availability. Similar barriers resulting in delayed presentation have been described
among other LMICs in Africa31–33. Based on a recent systematic analysis by Beaudoin et
al., additional barriers, which may influence this population but have not been previously
described include level of education and use of alternative medicine.27 Taken together, these
data advocate for educational and infrastructural interventions to promote early diagnosis,
timely referrals, comprehensive staging work-up, and evidence-based multidisciplinary care
for these patients.
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Given the late presentation of many cases, the relatively poor survival among this HNC
population is not surprising. The majority patients also appeared to lack 1) comprehensive
staging work-up for appropriate risk and treatment stratification, and/or 2) multimodality
oncologic treatment. Surgery and chemotherapy are common cornerstones in definitive HNC
management; however, only 8% of patients underwent surgery (due to a paucity of
oncologically-specialized otolaryngologists), while only 19% received chemotherapy (as a
result of toxicity concerns). Of those who received RT, the majority (57%) were treated with
non-definitive doses (defined here as an EQD2 < 60 Gy). Even among those treated
definitively, significant treatment delays were noted (2.5 months to RT start) and 35%
received doses less than 70 Gy - the literature-supported dose for many HNC subsites. Taken
together, these discrepancies contributed to the poor outcomes and lack of benefit noted
among RT subgroups.
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Aside from access-related concerns, our data provide some reassurance for the HIV-infected
population, as HIV-status did not appear to affect survival or toxicity outcomes among this
study population. Interestingly, the rate of HIV infection among our cohort (40%) was
higher than that of the general Botswana adult population aged 15 years and older (22.2% in
2019).11 This discrepancy is potentially attributable to an increased prevalence of HNC
among HIV-infected patients ([~2–3 fold).34–37 However, the high rate of ART utilization
mirrored that of the general Botswana population (85%),11 and HIV-infected patients in the
studied cohort had similar KPS and disease characteristics as their HIV-uninfected
counterparts. Regarding treatment, HIV patients were no more-or-less likely to receive
definitive RT or experience treatment-related toxicity than those not infected with HIV.
Taken together, these findings appear to indicate that HIV-status should not preclude
definitive management of patients with HNC.
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The primary limitation of this study is the relatively modest sample size and follow-up,
which may have affected the ability to detect survival differences among groups. The
specific cause of death for these patients was not captured, although most if not all are
assumed to result directly from tumor-related complications or progression, given the
advanced presentations and suboptimal treatment paradigms among this population. The
heterogeneity in HNC primaries and lack of comprehensive staging work-up for many
patients also limited granular comparisons across/within various subsites and tumor stages,
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and likely contributed to difficulties in optimally tailoring treatments. In addition, the lack of
HPV testing, an important prognostic indicator in HNC that has been associated with HIV
infection in other populations,38,39 limits exploration of any potential role of HPV infection
in this cohort. Furthermore, the poor survival among this population may conceal the
potential impact of HIV on outcomes. Nevertheless, these prospectively collected data offer
a unique perspective into practice patterns, survival, and toxicity among HNC patients in a
resource-limited setting with a high prevalence of HIV-infection.
CONCLUSION
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These findings highlight the late presentation, delayed treatment, and suboptimal outcomes
among HNC patients in Botswana despite government-sponsored care-alarming figures
likely echoed across other LMIC and SSA settings. Educational and infrastructural
interventions are warranted to promote earlier detection, timely referrals, access to
comprehensive staging work-up, and evidence-based multidisciplinary care for these
patients. Notably, a disproportionately high number of our patients were infected with HIV,
but HIV-status did not appear to affect survival or toxicity outcomes among our patients and
should thus not preclude definitive management for this HNC population.
Acknowledgments
The Mentored Patient Oriented Career Research Development Award (1-K08CA230170-01A1), Department of
Radiation Oncology, University of Pennsylvania, and Sub-Saharan African Collaborative HIV and Cancer
Consortia-U54 (1U54 CA190158-01) funded this effort.
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Fig. 1.
Survival outcomes of head-and-neck cancer patients in Botswana by radiation therapy intent:
no radiation (n = 48), non-definitive RT (n = 58), and definitive RT (n = 43).a Abbreviations:
RT, radiation therapy; Path, pathological.
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Fig. 2.
Survival outcomes by HIV status: infected (n = 59) versus uninfected (n = 90).
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90 (60)
Negative
†
†
36 (43)
≥ 20
Laryngoscope. Author manuscript; available in PMC 2021 May 01.
70 (47)
79 (53)
50–80
90–100
90 (50–100)
56 (58)
≥50
Median (range)
KPS
40 (42)
<50
Median (IQR)
54 (46–63)
62 (54)
≥12 (g/dL)
Weight (kg)
52 (46)
<12 (g/dL)
†
12 (10–13)
Median (IQR)
Hemoglobin
48 (57)
<20
Median (IQR)
19 (16–23)
68 (46)
≤50
BMI (kg/m2)
81 (54)
>50
Median (IQR)
53 (42–61)
60 (40)
Female
Age (years)
89 (60)
Male
Sex
59 (40)
Patients n (%)
Positive
HIV status
Variable
.99 (.60–1.66)
1.49 (.82–2.70)
2.73 (1.56–4.77)
1.74 (.85–3.55)
1.17 (.71–1.93)
1.18 (.70–1.98)
1.14 (.69–1.89)
HR (95% CI)
.997
.187
<.001
.129
.548
.54
.606
P Value*
Overall Survival, UVA
2.74 (1.53–4.91)
HR (95% CI)
.001
P Value*
Overall Survival, MVA
Relationship of clinical and treatment factors of study patients with head-and-neck cancers in Botswana to survival (n = 149).
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TABLE I.
McGinnis et al.
Page 14
‡
‡
†
48 (32)
None
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Laryngoscope. Author manuscript; available in PMC 2021 May 01.
18 (42)
25 (58)
≥3 months
<3 months
Median, Mos (IQR)
2.5 (1.6–5.4)
15 (35)
<70 Gy
Time from diagnosis to RT
28 (65)
70 (66–70)
≥70 Gy
Median, Gy (IQR)
Definitive EQD2
18 (42)
≤8 weeks
‡
25 (58)
>8 weeks
Median, days (IQR)
RT course length
57 (46–62)
58 (39)
‡
43 (29)
Non-definitive
42 (28)
Definitive
RT Indication
Non-SCC
SCC
107 (72)
94 (63)
Histology
55 (37)
Negative
20 (34)
Positive
Nodal disease
Non-IV
IV
38 (66)
27 (40)
Non-T4
‡
Stage (AJCC VII)
41 (60)
T4
Primary stage
Patients n (%)
Author Manuscript
Variable
1.50 (.58–3.90)
.78 (.30–2.06)
.60 (.23–1.57)
0.76 (.43–1.33)
1.46 (.80–2.66)
.79 (.47–1.35)
.86 (.37–2.02)
1.32 (.57–3.03)
HR (95% CI)
.405
.617
.299
.335
.213
.395
.73
.518
P Value*
1.90 (.92–3.90)
HR (95% CI)
.081
P Value*
Overall Survival, MVA
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Overall Survival, UVA
McGinnis et al.
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79 (53)
70 (47)
2015–2016
124 (83)
2017–2019
Treatment year
No
Yes
25 (17)
74 (50)
Bleeding symptoms
75 (50)
No
140 (94)
9 (6)
Yes
Painful symptoms
No
Yes
Prior malignancy
31 (21)
118 (79)
No
110 (74)
39 (26)
Yes
Alcohol use
No
Yes
Tobacco use
33 (22)
116 (78)
No
132 (89)
17 (11)
Yes
Married
No
Yes
Tuberculosis
29 (19)
120 (81)
No
137 (92)
12 (8)
Yes
Chemotherapy
No
Yes
Surgery
Patients n (%)
Author Manuscript
Variable
1.12 (.67–1.87)
.84 (.44–1.61)
1.29 (.78–2.12)
.82 (.30–2.27)
.98 (.52–1.84)
.70 (.37–1.31)
.91 (.49–1.68)
1.10 (.52–2.32)
1.04 (.56–1.92)
.17 (.02–1.20)
HR (95% CI)
.663
.6
.322
.706
.953
.264
.766
.796
.899
.075
P Value*
1.21 (.68–2.15)
.67 (.33–1.40)
.29 (.04–2.15)
HR (95% CI)
.513
.288
.226
P Value*
Overall Survival, MVA
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Overall Survival, UVA
McGinnis et al.
Page 16
13 (9)
9 (6)
Orbit
Skin
Cox proportional hazards analysis.
4 (3)
13 (9)
Nasopharynx
7 (5)
13 (9)
Oropharynx
Thyroid
14 (9)
Salivary
Unknown (neck)
14 (9)
Larynx
7 (5)
55 (37)
Oral cavity
Sinonasal
149
All patients
N/A
20.4 (19.1–21.6)
13.0 (0.0–26.1)
N/A
47.0 (N/A)
34.2 (8.0–60.5)
25.2 (13.3–37.2)
N/A
25.6 (16.0–35.2)
36.2 (N/A)
36.2 months (20.6–51.8)
N/A
41.7% (±22.2%)
38.1% (±19.9%)
75.0% (±15.3%)
61.5% (±13.5%)
57.7% (±14.7%)
51.6% (±16.4%)
84.4% (±10.2%)
51.9% (±15.8%)
52.9% (±7.1%)
58.2% (±4.4%)
2-Year OS (% ± SE)
BMI = body mass index; CI = confidence interval; HR = hazard ratio; IQR = interquartile range; MVA = multivariable; SCC = squamous cell carcinoma; UVA = univariate.
Staging limited by lack of comprehensive work-up, including fiberoptic nasopharyngolaryngoscopy and/or axial diagnostic imaging for all patients.
‡
Data not available for all patients.
†
*
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Median OS (95% CI)
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Patients (%)
Author Manuscript
H&N Sub-Site
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TABLE II.
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Differences Among HIV-Positive (n = 59) Versus HIV-Negative Patients (n = 90).
HIV-Negative (n = 90) No. Patients (%)
P Value
49 (41–56)
55 (41–64)
.084
Oral cavity
24 (41)
31 (34)
.002
Larynx
7 (12)
7 (8)
Salivary
6 (10)
8 (9)
Oropharynx
2 (3)
11 (12)
Variable
HIV-Positive (n = 59) No. Patients (%)
On ART?
Yes
50 (85)
No
9 (15)
Viral load*
>400
3 (10)
≤400
36 (90)
CD4 count*
Median (IQR)
400 (237–584)
Age (years)
Author Manuscript
Median, (IQR)
†
Sub-site
Nasopharynx
‡
Author Manuscript
2 (3)
11 (12)
Orbit
11 (19)
2 (2)
Skin
1 (2)
8 (9)
Sinonasal
1 (2)
6 (7)
Unknown (neck)
4 (7)
3 (3)
Thyroid
1 (2)
3 (3)
SCC
45 (76)
62 (69)
Non-SCC
14 (24)
28 (31)
‖
13 (22)
30 (33)
Non-definitive/none
46 (78)
60 (67)
4.1 (1.8–7.4)
2.3 (1.6–3.8)
.440
Yes
6 (10)
6 (7)
.542
No
53 (90)
84 (93)
50–80
30 (55.5)
40 (45.5)
90–100
25 (45.5)
48 (54.5)
Histology
§
.327
RT dose
Definitive
§
.137
Time to RT (months)
Median (IQR)
†
Surgery
§
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KPS*
¶
Primary stage
Laryngoscope. Author manuscript; available in PMC 2021 May 01.
§
.290
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Variable
HIV-Positive (n = 59) No. Patients (%)
HIV-Negative (n = 90) No. Patients (%)
P Value
T4
12 (60)
29 (60)
.974
Non-T4
8 (40)
19 (40)
IV
13 (72)
25 (62.5)
Non-IV
5 (28)
15 (37.5)
Positive
21 (36)
34 (38)
Negative
38 (64)
56 (62)
Yes
9 (15)
20 (22)
No
50 (85)
70 (78)
Yes
6 (10)
3 (3)
No
53 (90)
87 (97)
§
¶
Stage (AJCC VII)
Nodal disease
§
.471
¶
§
.787
Chemotherapy
§
.293
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Prior malignancy
§
.088
*
Data not available for all patients.
†
Continuous variables were compared with the Mann-Whitney test.
‡
Categorical variables were compared via Fisher’s exact test.
§
Categorical variables were compared via χ2 tests.
‖
Defined as EQD2 ≥60 Gy.
¶
Author Manuscript
Staging limited by lack of comprehensive work-up, including fiberoptic nasopharyngolaryngoscopy and/or axial diagnostic imaging for all
patients.
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TABLE III.
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Details of Patients who Received Radiation Therapy and Associations with Toxicity (n = 101).
Variable
Patients (%)
Acute, Grade ≥ 2 OR (P value)*
Acute, Grade ≥ 3 OR (P value)*
Any Late Event OR (P value)*
44 (44%)
30 (30%)
11 (11%)
2.44 (.075)
4.04 (.034)
1.54 (.595)
1.60 (.279)
0.96 (.922)
0.83 (.795)
1.77 (.166)
1.95 (.135)
2.40 (.175)
0.35 (.012)
0.44 (.065)
0.38 (.145)
3.37 (.032)
6.04 (.012)
1.09 (.919)
0.45 (.087)
0.74 (.527)
0.47 (.314)
1.40 (.503)
1.61 (.344)
0.44 (.333)
0.81 (.601)
0.85 (.710)
0.34 (.131)
0.81 (.697)
0.73 (.577)
0.20 (.064)
0.39 (.142)
0.32 (.084)
1.00 (.999)
0.69 (.378)
1.00 (.996)
0.99 (.984)
1.93 (.138)
2.12 (.107)
1.49 (.554)
Primary sub-site
†
Mucosal
Non-mucosal
HIV status
Positive
Negative
RT length (days)
>8 weeks
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≤8 weeks
EQD2 Dose
<60 Gy
≥60 Gy
‡
BMI (kg/m2)
<20
≥20
‡
Hemoglobin
<12 (g/dL)
≥12 (g/dL)
‡
Weight (kg)
Author Manuscript
<50
≥50
‡
KPS
50–80
90–100
§
Primary stage
T4
Non-T4
§
Stage (AJCC VII)
IV
Non-IV
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Nodal disease
§
Positive
Negative
Chemotherapy
Yes
No
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McGinnis et al.
Variable
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Acute, Grade ≥ 2 OR (P value)*
Acute, Grade ≥ 3 OR (P value)*
Any Late Event OR (P value)*
1.24 (.598)
1.34 (.515)
1.28 (.710)
0.20 (<.001)
0.12 (<.001)
0.254 (.091)
Patient age
>50 years
≤50 years
Treatment year
2017–2019
2015–2016
*
Logistic regression analysis.
†
Defined as oral cavity, larynx, oropharynx, nasopharynx, or sinonasal tumors.
‡
Data not available for all patients.
§
Staging limited by lack of comprehensive work-up, including fiberoptic nasopharyngolaryngoscopy and/or axial diagnostic imaging for all
patients.
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OR = odds ratio; RT = radiation therapy.
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