HEAD AND NECK MANIFESTATIONS OF HIV DISEASE

(20-Mark Answer - RGUHS Standard)

INTRODUCTION

DIAGRAM 1: Anatomical Sites of HIV Head and Neck Manifestations

CLASSIFICATION (KJ Lee's / Cummings)

1. Infectious/Inflammatory conditions as a result of immunodeficiency
2. Complicated infections as a result of immunodeficiency
3. Malignancy related to immunodeficiency
4. AIDS-related illness (systemic conditions with head and neck involvement)

FLOWCHART: Classification and Management of HIV Head and Neck Manifestations

CD4 COUNT AND CLINICAL STAGING (WHO 2007)

A. ORAL CAVITY MANIFESTATIONS

1. Oral Candidiasis (Thrush)

• Pseudomembranous form (thrush): White plaques on buccal mucosa, tongue, palate - easily wiped off leaving erythematous base
• Erythematous (atrophic) form: Red patches on hard/soft palate and dorsal tongue
• Angular cheilitis: Cracking and erythema at oral commissures
• Caused by Candida albicans
• Treatment: Topical nystatin or clotrimazole; systemic fluconazole for refractory cases
• Presence of oral candidiasis in an otherwise healthy adult is an indicator for HIV testing (Scott-Brown's Vol 1)

2. Oral Hairy Leukoplakia (OHL)

• White, corrugated/hairy lesions on the lateral borders of the tongue - cannot be wiped off (unlike candida)
• Caused by Epstein-Barr Virus (EBV) reactivation
• A pathognomonic indicator of HIV infection - occurrence strongly suggests CD4 count <300
• Virtually diagnostic: biopsy shows hyperparakeratosis with "hair-like" projections and koilocytic cells
• Treatment: Responds to HAART; topical retinoids or acyclovir for symptom relief
• Dhingra (Diseases of Ear, Nose and Throat): Listed as a hallmark opportunistic oral lesion in AIDS patients

3. Aphthous Ulcers

• Major aphthous ulcers - larger (>1 cm), deeper, more painful, more frequent in HIV
• Classified as: Minor (<1 cm), Major (>1 cm), and Herpetiform
• Etiology unclear; may relate to immune dysregulation
• Treatment: Topical corticosteroids (triamcinolone paste), thalidomide for severe/refractory cases

4. Periodontal Disease

• Linear Gingival Erythema (LGE): Fiery red band at the gingival margin, out of proportion to plaque, persists despite scaling
• Necrotizing Ulcerative Gingivitis/Periodontitis/Stomatitis (NUG/NUP/NUS): Progressive recession, bleeding, tissue sloughing, malodor, loss of interdental papillae - a spectrum of the same pathology
• Management: Chlorhexidine + nystatin mouthwash topically; dental referral; debridement of necrotic tissue; systemic metronidazole for failure

B. SALIVARY GLAND MANIFESTATIONS

Benign Lymphoepithelial Cysts (BLECs) / Parotid Cysts

• Most common parotid lesion in HIV patients (approximately 75% of parotid lesions)
• Parotid is most commonly affected due to intraparotid lymph nodes (KJ Lee's, p. 236)
• Particularly prevalent in pediatric HIV patients - up to 18% of presenting complaints
• Bilateral in up to 80% of cases (though may present unilaterally clinically)
• Etiology: viral inflammation causing cystic transformation of intraparotid lymph nodes
• Present asymptomatically; compression of parotid ducts can cause pain/sialadenitis
• Cervical lymphadenopathy is present in up to 70-80% of cases simultaneously
• Diagnosis: FNA (cytology), CT/MRI, ultrasound
• Treatment: HAART leads to regression; aspiration for cosmesis; sclerotherapy; surgery rarely required
• Must exclude: lymphoma, Kaposi sarcoma, metastatic cutaneous malignancy

Diffuse Infiltrative Lymphocytosis Syndrome (DILS)

• CD8+ lymphocytic infiltration of salivary glands causing bilateral parotid swelling
• Associated with sicca symptoms (dry mouth, dry eyes)
• Differs from Sjogren's syndrome serologically (anti-Ro, anti-La negative)

C. CERVICAL LYMPHADENOPATHY

• Defined as lymphadenopathy >1 cm in 2 or more extra-inguinal sites, lasting >3 months
• Cervical nodes most commonly involved
• Nodes: small, symmetrical, non-tender
• Biopsy reveals follicular hyperplasia - no specific treatment required
• Occurs in up to 70% of patients in the asymptomatic phase (Scott-Brown's Vol 1, p. 278)

• Non-Hodgkin's lymphoma (NHL)
• Hodgkin's lymphoma
• Tuberculosis (the most important opportunistic infection to exclude in India)
• Kaposi's sarcoma nodal involvement
• Syphilis
• Metastatic solid organ malignancy

D. NOSE AND PARANASAL SINUS MANIFESTATIONS

Rhinitis and Nasal Obstruction

• Adenoidal hypertrophy can cause nasal obstruction and recurrent otitis media
• Any non-pediatric patient with adenoid hypertrophy should be tested for HIV (Scott-Brown's)
• Hypertrophy of any Waldeyer's ring tissue may occur
• KS and Non-Hodgkin's lymphoma can arise in the nasal cavity/nasopharynx
• KS can also arise from the nasal septum

Sinusitis - CD4-dependent microbiology:

Invasive Fungal Sinusitis

• Occurs with CD4 <50 cells/mm3
• Most feared sinonasal complication - can be rapidly fatal
• Presents with facial pain, proptosis, periorbital swelling, cranial nerve palsies
• CT shows subtle bony erosion with extension into infratemporal fossa (see image below)
• Treatment: IV amphotericin B + aggressive surgical debridement

CT Scan - Invasive Fungal Sinusitis in Advanced HIV:

E. OTOLOGIC MANIFESTATIONS

External Ear

• Osteomyelitis of skull base causing facial nerve/cranial nerve dysfunction
• Causative agent: Pseudomonas aeruginosa (most common)
• In very low CD4 count: Aspergillus - invasive and potentially fatal
• Diagnosis: CT temporal bone or Technetium-99m bone scan
• Treatment: Pseudomonas: 6-8 weeks antipseudomonal antibiotics (3rd-gen cephalosporin + ciprofloxacin or aminoglycoside); Aspergillus: IV amphotericin B + surgical debridement

• Can infect external auditory canal, middle ear, and mastoid bone
• Presents as cyst or polyp; may occlude EAC or spread to middle cranial fossa
• Diagnosis: Biopsy
• Treatment: Trimethoprim/sulphamethoxazole ± dapsone

Middle Ear

• Most common otologic entities: serous and recurrent otitis media
• Etiologies: Eustachian tube dysfunction, nasopharyngeal neoplasms, adenoid hypertrophy, sinusitis/allergy
• Chronic otitis media and tympanic membrane perforations more prevalent in HIV-positive children in Sub-Saharan Africa
• Conductive and sensorineural hearing loss reported

Sensorineural Hearing Loss (SNHL)

• Multifactorial in HIV:
  1. Direct viral neurotoxicity to cochlea/auditory nerve
  2. Opportunistic infections (CMV, cryptococcal meningitis)
  3. Ototoxic medications (especially aminoglycosides, cisplatin used in treatment)
  4. CNS lymphoma
• Up to 49% of HIV-positive patients may have some degree of hearing loss

F. PHARYNGEAL AND LARYNGEAL MANIFESTATIONS

Pharyngitis

• A common presentation of acute HIV seroconversion syndrome (2-4 weeks post-exposure)
• Exudative or non-exudative pharyngitis mimicking EBV mononucleosis
• Associated with: fever, cervical lymphadenopathy, maculopapular rash, oropharyngeal ulcers, meningoencephalitis
• Heterophile antibody test (Monospot) is usually negative (key distinguishing feature)
• Any mononucleosis-like illness: offer HIV test (UK guidelines)

Larynx

• Candidal laryngitis - hoarseness, odynophagia, dysphonia
• KS of larynx - can cause airway compromise
• SCC of larynx - increased risk in HIV patients
• Herpes simplex laryngitis, CMV laryngitis in advanced disease

G. HIV-ASSOCIATED MALIGNANCIES OF THE HEAD AND NECK

1. AIDS-DEFINING MALIGNANCIES

Kaposi's Sarcoma (KS)

• Caused by Human Herpesvirus 8 (HHV-8)
• Incidence in HIV patients ~5%; 70% of all KS lesions occur in the head and neck
• Cummings Table (10.4): Most common sites: skin, oral mucosa, lymph nodes
• Clinical features:
  • Skin: violaceous/brownish-red macules, papules, nodules - painless initially
  • Oral mucosa: classically raised, red lesions on hard palate; may ulcerate
  • Lesion size variable (mm to cm); may be flat, raised, or nodular
• Diagnosis: Clinical + biopsy (shows spindle cells, vascular spaces, HHV-8 staining)
• Treatment:
  • HAART is the mainstay - immune recovery leads to regression
  • Advanced disease: localized radiotherapy (good control, but HIV patients more prone to radiation side effects)
  • Surgical excision for local control (recurrence common even with clear margins)
  • Other options: topical retinoids, intralesional chemotherapy, laser coagulation, cryotherapy
• Marked decrease in incidence since introduction of HAART (Cummings, p. 4178)

AIDS-Related Non-Hodgkin Lymphoma (NHL)

• Head and neck involved in two-thirds of cases of AIDS-NHL
• Extranodal disease twice as common in AIDS-NHL compared to non-HIV-associated NHL
• Extranodal head and neck sites: oral cavity, sinonasal tract, salivary glands, Waldeyer's ring
• More likely to have advanced disease at presentation
• Plasmablastic lymphoma: A rare aggressive B-cell lymphoma strongly associated with HIV, primarily arises in oral cavity - reviewed by Xu et al., 2025 in Head Neck journal (PMID: 41025371)
• Treatment: R-CHOP chemotherapy; HAART continuation

2. NON-AIDS-DEFINING MALIGNANCIES

Hodgkin Lymphoma (HL)

• Nearly universal cervical lymph node involvement
• More aggressive course in HIV
• Treatment: ABVD + HAART

Squamous Cell Carcinoma (SCC)

• HIV patients have a 3-fold higher age-standardized incidence of HPV-associated and HPV-negative head and neck SCC compared to the general population (Goldman-Cecil Medicine)
• Sites: larynx, oral cavity, oropharynx
• Lip SCC considered a distinct cutaneous risk
• A recent study from New York showed HIV infection in 5% of head and neck cancer patients; in patients under 45, HIV was present in >20%
• More aggressive course compared to immunocompetent patients

Nonmelanoma Skin Cancer (NMSC)

• HIV patients more likely to develop BCC
• Transplant recipients more likely to develop cutaneous SCC
• Both: more aggressive course

H. NEUROLOGICAL MANIFESTATIONS IN HEAD AND NECK

• Facial nerve palsy: Bilateral facial nerve palsies reported; usually represent systemic disease
  • Work-up: serology for syphilis, CMV, HSV, HZV, EBV; MRI brain + CSF analysis
• Cranial neuropathies: From skull base osteomyelitis (MOE), CNS lymphoma, cryptococcal meningitis
• Patients with low CD4 count may present with CNS disease with few/ambiguous clinical signs - low threshold for neuroimaging and lumbar puncture

I. HIV TESTING IN OTOLARYNGOLOGY PRACTICE

• Unexplained oral candidiasis
• Hairy leukoplakia of the tongue
• Atypical head and neck cancers
• Parotid cysts
• Cervical lymphadenopathy
• Chronic parotitis
• Pyrexia of unknown origin
• Non-pediatric adenoid hypertrophy

J. TREATMENT - HAART AND IMPACT ON HEAD AND NECK DISEASE

1. NRTIs (Nucleoside Reverse Transcriptase Inhibitors): Terminate proviral DNA replication (e.g., zidovudine, tenofovir) - backbone of therapy
2. NNRTIs (Non-Nucleoside RTIs): Bind directly to reverse transcriptase active site (e.g., efavirenz, nevirapine)
3. Protease Inhibitors (PIs): Block viral particle maturation; complex absorption kinetics (e.g., lopinavir/ritonavir)
4. Integrase Inhibitors: Block viral DNA integration (e.g., dolutegravir, raltegravir)
5. Entry/Fusion Inhibitors: Reserved for intolerant patients or resistant infection

• Marked decrease in AIDS-defining malignancies (KS, NHL) since HAART introduction
• Resolution of BLECs and parotid disease with immune reconstitution
• However, non-AIDS-defining malignancies (head and neck SCC, lung, liver) continue to rise
• Immune Reconstitution Inflammatory Syndrome (IRIS) - paradoxical worsening of conditions after HAART initiation (e.g., tuberculous lymphadenitis flare)

RECENT ADVANCES (2021-2026)

1. Plasmablastic Lymphoma: Growing recognition of this oral cavity-predominant, HIV-associated aggressive B-cell lymphoma. Xu et al. Head Neck 2025 (PMID 41025371) document rising case series; strongly EBV and HIV co-associated.
2. EBV-HIV co-infection in Head and Neck Lymphomas: Xoki et al., Oral Surg Oral Med 2026 (PMID 40975699) demonstrated the incidence and role of EBV and HIV in head and neck lymphomas, confirming synergistic oncogenic roles.
3. HIV-HPV interaction in Head and Neck SCC: Growing evidence that HIV-infected individuals have 3-fold higher incidence of HPV-associated oropharyngeal SCC. Vaccination against HPV (Gardasil 9) is now recommended for all HIV-positive patients regardless of age.
4. Dolutegravir-based regimens are now first-line globally (WHO 2023 guidelines), offering better tolerability and higher barrier to resistance compared to older HAART regimens, leading to improved head and neck disease control.
5. Pre-Exposure Prophylaxis (PrEP): Tenofovir/emtricitabine daily use has significantly reduced new HIV infections in high-risk populations, with attendant reduction in head and neck HIV manifestations in high-income countries.
6. Oral Microbiome: Recent research shows HIV-positive patients have a dysbiotic oral microbiome independent of antiretroviral use, contributing to periodontal disease severity.
7. Hearing Loss Screening: Updated recommendations for formal audiological screening in all HIV-positive patients given the high prevalence (up to 49%) of subclinical SNHL from combined viral, opportunistic, and drug-related ototoxicity.

SUMMARY TABLE: Head and Neck Manifestations of HIV

REFERENCES (Standard Textbooks for RGUHS)

1. Scott-Brown's Otorhinolaryngology Head and Neck Surgery, 8th Edition - Vol 1, Chapter 23: HIV and the ENT Surgeon, pp. 277-282
2. Cummings Otolaryngology Head and Neck Surgery, 7th Edition - Chapter 10: Immunodeficiency and ENT, Table 10.3-10.4, pp. 4141-4180
3. KJ Lee's Essential Otolaryngology, 11th Edition - Chapter 11: Head and Neck Manifestations of HIV, pp. 233-244
4. Dhingra PL, Dhingra S - Diseases of Ear, Nose and Throat and Head and Neck Surgery - Chapter on AIDS and ENT Manifestations
5. Hazarika P - Textbook of Ear, Nose and Throat and Head and Neck Surgery - HIV manifestations section
6. Zakir Hussain - ENT Short Cases - OSCE preparation chapter on AIDS/HIV
7. Stell and Maran's Head and Neck Surgery - Immune-mediated head and neck disease chapter
8. Goldman-Cecil Medicine, 27th Edition - Human Immunodeficiency Virus section
9. Xu A et al. Oral Plasmablastic Lymphoma: Case Series and Literature Review. Head Neck. 2025 Dec. PMID: 41025371
10. Xoki B et al. The incidence and role of EBV and HIV in head and neck lymphomas. Oral Surg Oral Med Oral Pathol Oral Radiol. 2026 Jan. PMID: 40975699