Oncogenic DNA Viruses

Slide 1 · Oncogenic DNA Viruses

Mechanisms of viral carcinogenesis and clinicopathologic associations

Persistent infection

Host-cell dysregulation

Malignant transformation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Identify the oncogenic human DNA viruses named.

Explain how persistent infection subverts cell-cycle control or host immunity.

Differentiate direct viral effects from inflammation-driven carcinogenesis.

Link major virus–tumor associations to their pathogenic mechanisms.

Virus–host interaction

Oncogenic mechanism

Tumor association

Slide 3 · Five human DNA viruses implicated in cancer

HPV, EBV, HBV, Merkel cell polyomavirus, and HHV8 are the principal agents listed.

They differ in target cells, persistence, and tumor spectrum.

HCV is included for comparison but has an RNA genome.

DNA virus group

Different cellular targets

Distinct tumor pathways

Slide 4 · Virus–tumor associations are not interchangeable

Virus

Major tumor association

Dominant teaching mechanism

HPV

Cervical, anogenital, head/neck squamous cancer

E6/p53 and E7/RB

EBV

B-cell lymphomas; nasopharyngeal carcinoma

Latency, signaling, immune context

HBV

Hepatocellular carcinoma

Chronic inflammation; HBx/integration

HHV8 / KSHV

Kaposi sarcoma; selected B-cell disorders

Lytic/latent programs; immune suppression

Merkel polyomavirus

Merkel cell carcinoma

Integrated viral genome; growth-control proteins

Slide 5 · An infection is not itself equivalent to malignancy

Most infections do not culminate in cancer.

Persistence, permissive host conditions, and additional alterations can be decisive.

Latency may allow viral genomes to persist without productive cell lysis.

Initial infection

Persistent or latent state

Cofactors + acquired changes

Selected malignant clone

Slide 6 · Three mechanistic routes to virus-associated cancer

Viral proteins can directly impair tumor suppressors and promote proliferation.

Viral latency may expand an infected cell pool while evading immune elimination.

Chronic immune-mediated tissue injury can promote regeneration and mutation.

Direct cell-cycle disruption

B-cell immortalization / immune failure

Chronic injury / regeneration

Slide 7 · Host T-cell immunity modifies oncogenic risk

Effective cytotoxic responses restrain EBV-transformed B cells.

HIV-associated immunodeficiency promotes persistent HPV infection and HHV8-related disease.

T-cell surveillance may prevent progression of MCV-infected cells.

Oncogenic viral persistence

T-cell containment

Failure of containment → risk

Slide 8 · Genetic collaboration explains delayed transformation

HPV E6 and E7 can immortalize keratinocytes without making them tumorigenic alone.

Burkitt lymphoma requires MYC dysregulation in addition to permissive B-cell proliferation.

Viral infection creates a context in which further alterations become consequential.

Viral growth advantage

Additional genetic events

Cancer clone emerges

Slide 9 · Low-risk and high-risk HPV have different outcomes

Low-risk HPV-6 and HPV-11 predominantly cause genital warts.

High-risk types, including HPV-16 and HPV-18, are associated with squamous carcinomas.

Difference in E6/E7 binding activity helps explain differential cancer risk.

Low risk → papilloma

High risk → persistent oncogenic activity

Slide 10 · Anatomic distribution of high-risk HPV cancers

Cervical squamous carcinoma is a key HPV-associated malignancy.

Anogenital squamous cancers are included in the association.

In the head and neck, tonsillar mucosa is highlighted.

Cervix

Anogenital region

Tonsillar mucosa

Slide 11 · HPV genome state differs between warts and cancers

In benign warts, viral genomes are generally maintained as episomes.

In cancers, viral DNA is commonly integrated into host chromosomal DNA.

Integration is implicated in altered expression of oncogenic viral genes.

Episomal viral DNA

Integrated viral DNA

Slide 12 · Clonal integration is evidence of early viral involvement

Integration sites vary across tumors; No single host locus is required.

Within a tumor, integration patterns are clonal.

Clonality supports expansion of a progenitor bearing the viral event.

Random integration site

Shared site within clone

Clonal expansion

Slide 13 · E2 loss derepresses the E6/E7 oncogenes

Integration disrupting the E1/E2 region.

Loss of the E2 repressor increases expression of E6 and E7.

The consequence is sustained interference with host growth checkpoints.

E1/E2 disruption

E2 repression lost

E6 + E7 expression rises

Slide 14 · E6 accelerates degradation of p53

E6 binds p53 and facilitates its destruction.

Loss of p53 impairs damage-response restraints on abnormal cells.

High-risk HPV E6 binds p53 more avidly than low-risk E6.

E6 binds p53

P53 degradation

Impaired tumor-suppressor restraint

Slide 15 · E6 also supports replicative immortality

E6 stimulates expression of telomerase reverse transcriptase (TERT).

TERT is the catalytic subunit of telomerase.

Telomerase activity helps infected cells bypass senescence.

E6

TERT ↑

Telomerase ↑

Cellular immortalization

Slide 16 · E7 releases the RB–E2F cell-cycle brake

RB normally sequesters E2F transcription factors.

E7 binds RB and releases E2F.

Available E2F promotes transcription required for G1/S progression.

Before E7 binding

RB restrains E2F

After high-risk E7 binding

E7 binds RB

E2F released

G1/S progression

Slide 17 · High-risk E7 binds RB with greater affinity

The E7 proteins of high-risk HPVs bind RB more strongly than low-risk E7.

This strengthens the proliferative impact of a persistent infection.

Oncogenic potential is related to functional properties, not just presence of viral DNA.

Low-risk E7 / RB

High-risk E7 / RB

Slide 18 · E7 removes additional G1/S restraints

E7 inactivates the CDK inhibitors p21 and p27.

High-risk E7 can bind and probably activate cyclins A and E.

These combined actions favor progression through the cell cycle.

P21 / p27 inhibition

Cyclin A / E engagement

G1/S checkpoint weakened

Slide 19 · E6 and E7 attack complementary safeguards

Oncoprotein

Principal host target

Pathologic consequence

E6

p53 degradation

Reduced damage-dependent restraint

E6

TERT expression

Maintenance of telomeres / immortalization

E7

RB binding, E2F release

G1/S progression

E7

p21 / p27 inhibition; cyclins A/E

Additional cell-cycle acceleration

Slide 20 · Cell-cycle deregulation is not full transformation

HPV-16, -18 or -31 DNA can immortalize human keratinocytes in vitro.

That tumor formation requires an additional altered RAS gene in this model.

Transformation therefore has a multistep genetic requirement.

Keratinocyte + high-risk HPV

Immortalized cell

Additional RAS alteration

Tumorigenic cell in model

Slide 21 · Persistent infection distinguishes many high-risk cases

A high proportion of women clear high-risk HPV infections.

The subgroup with persistent infection bears greater cervical-cancer risk.

The long interval between infection and cancer supports additional events.

High-risk infection

Clearance → lower risk

Persistence → continuing risk

Slide 22 · HIV co-infection increases persistence risk

HIV co-infection as an important predictor of persistence.

The proposed explanation is defective T-cell immune control.

The relevant pathway is prolonged high-risk viral exposure, not HIV as a DNA virus.

HIV-associated T-cell dysfunction

Reduced HPV control

Persistent infection

Slide 23 · Nonviral cofactors influence HPV carcinogenesis

Cigarette smoking and coexisting microbial infections.

Dietary deficiencies and hormonal changes are also noted.

These factors modify risk but do not replace the etiologic role of high-risk HPV.

Persistent HPV

Host / environmental cofactors

Additional cellular alterations

Slide 24 · Why HPV vaccination prevents cancer

Preventing high-risk HPV infection interrupts the initiating viral exposure.

Vaccine effectiveness as strong causal evidence for cervical cancer.

Vaccination illustrates prevention upstream of somatic transformation.

HPV infection prevented

Persistent oncogene exposure prevented

Cervical cancer risk reduced

Slide 25 · Apply the HPV mechanism to a cervical lesion

A lesion contains integrated high-risk HPV DNA and abundant E6/E7 expression.

Predict the status of p53 regulation, RB-bound E2F, and telomerase.

Which finding reflects viral oncogene activity rather than an inherited TP53 mutation?

E6 → p53 degradation

E7 → RB/E2F release

E6 → TERT ↑

Slide 26 · EBV-associated tumors involve several lineages

B-cell lymphomas and nasopharyngeal carcinoma.

Other EBV-related lymphomas, carcinomas, and rare sarcomas are described.

Tumor phenotype and immune context shape the mechanism.

B-cell proliferations

Epithelial carcinomas

Other rare neoplasms

Slide 27 · EBV enters B cells through CD21

EBV surface glycoproteins recognize complement receptor CD21.

Binding facilitates B-cell infection, likely in the tonsils after salivary exposure.

The initially infected B cell provides a long-lived latent reservoir.

B cell

Viral surface protein

CD21 receptor

Schematic — receptor-mediated B-cell entry

Slide 28 · EBV latency persists as a circular episome

The latent EBV genome remains extrachromosomal.

Latent infection does not require ongoing productive viral replication.

Viral gene expression supports prolonged survival and proliferation of infected cells.

Circular viral episome

Latent viral proteins

Immortalized B-cell population

Slide 29 · LMP1 mimics constitutive CD40 signaling

Latent membrane protein 1 (LMP1) behaves like an active CD40 receptor.

Normally, helper T-cell CD40 signals support B-cell growth.

LMP1 supplies an autonomous growth and survival signal.

Physiologic CD40 ligation

LMP1 constitutive mimic

Slide 30 · LMP1 activates NF-κB and JAK/STAT

These pathways normally transmit growth and survival cues.

In EBV-infected cells they can operate without external helper T-cell stimulation.

The result is autonomous B-cell expansion and survival.

LMP1

NF-κB / JAK–STAT

B-cell proliferation and survival

Slide 31 · LMP1 promotes resistance to apoptosis

LMP1 activates the antiapoptotic factor BCL2.

Survival signals allow an enlarged pool of infected B cells to persist.

Persistence creates opportunities for secondary oncogenic alterations.

LMP1

BCL2 activation

Apoptotic resistance

Slide 32 · EBNA2 mimics activated Notch signaling

Epstein–Barr nuclear antigen 2 (EBNA2) behaves like activated Notch.

It changes host transcription rather than acting as a host DNA mutation.

Robbins specifically names cyclin D and SRC-family genes among its targets.

EBNA2

Host transcription ↑

Cyclin D / SRC-family targets

Slide 33 · EBV immune evasion sustains latency

Some EBV genes limit antigen presentation.

Other products blunt NK-cell and T-cell responses.

Reduced recognition favors the establishment of a persistent infected-cell reservoir.

Viral immune evasion

Antigen display / immune response impaired

Latent persistence

Slide 34 · Normal T cells control EBV-driven B-cell expansion

EBV growth-driving proteins are strongly immunogenic.

Cytotoxic T cells usually contain the resulting polyclonal B-cell proliferation.

The clinical outcome may be asymptomatic infection or infectious mononucleosis.

EBV-infected B cells expand

Cytotoxic T-cell response

Infected clone restrained

Slide 35 · T-cell failure permits uncontrolled B-cell growth

When T-cell immunity is defective, EBV-transformed B cells may proliferate rapidly.

This mechanism is important in AIDS and in transplant immunosuppression.

Immune context is therefore causally central, not merely associated.

T-cell impairment

EBV B-cell escape

Lymphoproliferation / lymphoma

Slide 36 · Burkitt lymphoma: EBV association depends on setting

More than 90% of endemic Burkitt lymphomas are EBV positive.

Only 15%–20% of tumors outside endemic regions harbor EBV.

Morphologically similar tumors can therefore have different viral associations.

Endemic: >90% EBV+

Outside endemic areas: 15–20% EBV+

Slide 37 · Geography points to cofactors in endemic Burkitt lymphoma

Endemic Burkitt lymphoma is described in central Africa and New Guinea.

EBV itself is nearly ubiquitous, whereas the tumor is geographically clustered.

Concomitant infections such as malaria as cofactors.

Widespread EBV infection

Regional immune cofactors

Endemic lymphoma risk

Slide 38 · MYC dysregulation is crucial in Burkitt lymphoma

Nearly all Burkitt lymphomas have an MYC-associated translocation.

The classic event is t(8;14); Alternative MYC translocations occur.

MYC dysregulation drives transformation beyond EBV-induced proliferation.

Persistent B-cell pool

MYC translocation

Malignant B-cell clone

Slide 39 · Proposed sequence for endemic Burkitt lymphoma

EBV infection expands B cells; Malaria-associated immune impairment can prolong expansion.

Cells that reduce immunogenic viral proteins may survive immune selection.

A subsequent MYC event can generate overt lymphoma.

EBV-driven B-cell proliferation

Immune selection / persistent cells

MYC deregulation

Burkitt lymphoma

Slide 40 · Why Burkitt lymphoma lacks growth-driving viral antigens

Burkitt lymphoma cells generally do not express LMP1 or EBNA2.

These antigens are expressed in EBV-immortalized B-cell lines.

This contrast supports immune selection plus acquired host oncogenic changes.

Immortalized B cell: LMP1 / EBNA2

Burkitt cell: Low growth-antigen expression

Slide 41 · EBV contributes indirectly to Burkitt transformation

Robbins characterizes EBV primarily as a polyclonal B-cell mitogen in this setting.

An expanded precursor pool favors acquisition and selection of MYC alterations.

The same MYC pathway is implicated in EBV-negative sporadic disease.

Mitogenic expansion

Secondary MYC alteration

Transformed clone

Slide 42 · Immunosuppression-related tumors use a different route

Post-transplant and AIDS-associated EBV lymphoproliferations often express LMP1/EBNA2.

They usually lack the MYC translocations characteristic of Burkitt lymphoma.

Some arise in extranodal sites, including gut or central nervous system.

Loss of T-cell surveillance

Viral growth proteins retained

B-cell lymphoproliferation

Slide 43 · Early EBV lymphoproliferation may be polyclonal

The earliest immunodeficiency-associated expansions may involve many B-cell clones.

Some progress to a monoclonal neoplasm.

Polyclonality does not guarantee a harmless clinical course.

Polyclonal expansion

Clonal selection

Monoclonal neoplasm

Slide 44 · Immune restoration can suppress EBV-driven growth

Reducing immunosuppression after transplant may restore T-cell restraint.

EBV lymphoproliferations can regress when immunity returns.

This directly demonstrates the role of host immune surveillance.

Immunosuppression reduced

T-cell immunity restored

EBV proliferation restrained

Slide 45 · Nasopharyngeal carcinoma has a strong EBV link

EBV in virtually all nasopharyngeal carcinomas studied.

Within a tumor the viral genome has a clonal configuration.

Clonality indicates infection preceded expansion of the malignant population.

EBV infection

Clonal viral genome

Nasopharyngeal carcinoma

Slide 46 · Nasopharyngeal carcinoma still needs cofactors

The cancer is endemic in southern China, parts of Africa, and Inuit populations.

Geographic clustering is not explained by widespread EBV infection alone.

Host genetics or environmental exposures likely modify risk.

Widespread infection

Regional predisposition

Carcinoma development

Slide 47 · LMP1 changes signaling in epithelial tumors

LMP1 is expressed in nasopharyngeal carcinoma.

Activation of NF-κB can increase VEGF, FGF2, MMP9, and COX2.

These products are implicated in the supportive oncogenic microenvironment.

LMP1

NF-κB

VEGF / FGF2 / MMP9 / COX2

Slide 48 · A lymphocyte-rich tumor can still evade immunity

Nasopharyngeal carcinoma often has a conspicuous T-cell infiltrate.

The infiltrate does not necessarily eliminate EBV-positive tumor cells.

Tumor PD-L1 expression and responses to PD-1/PD-L1 blockade.

T-cell infiltrate present

Immune evasion / PD-L1

Tumor persists

Slide 49 · EBV-associated B-cell and epithelial cancers differ

Tumor setting

Key EBV relationship

Additional determinant

Endemic Burkitt lymphoma

EBV-positive in most; LMP1/EBNA2 not expressed by tumor

MYC translocation; regional cofactors

Immunodeficiency-associated B-cell tumors

LMP1/EBNA2 often retained

Defective T-cell surveillance

Nasopharyngeal carcinoma

Clonal EBV; epithelial LMP1 signaling

Geographic / host cofactors; immune evasion

Slide 50 · Apply immune surveillance to an EBV-positive mass

A transplant recipient develops an extranodal EBV-positive B-cell proliferation.

LMP1 and EBNA2 are expressed; No MYC translocation is detected.

Which mechanism distinguishes this from endemic Burkitt lymphoma?

T-cell suppression

LMP1 / EBNA2 expression

Growth without MYC event

Slide 51 · HBV and HCV strongly associate with hepatocellular carcinoma

70%–85% of HCC worldwide to HBV or HCV infection.

HBV is a DNA virus; HCV is an RNA virus discussed as a comparator.

Neither infection makes malignant transformation inevitable.

HBV: DNA

HCV: RNA

Shared HCC outcome

Slide 52 · Chronic injury is the dominant carcinogenic route

Persistent viral hepatitis causes cycles of hepatocyte death and regeneration.

Inflammatory mediators sustain compensatory cell division.

Proliferating cells accumulate opportunities for genomic injury.

Chronic infection

Hepatocyte injury

Compensatory regeneration

Genomic damage

Slide 53 · Immune-derived factors support liver cell proliferation

Activated immune cells produce cytokines, growth factors, and chemokines.

These mediators promote survival, remodeling, and angiogenesis.

A response intended for repair can sustain pro-oncogenic regeneration.

Activated immune cells

Bioactive mediators

Hepatocyte growth + remodeling

Slide 54 · Inflammatory reactive oxygen species damage DNA

Chronic inflammatory cells can generate reactive oxygen species.

Oxidative stress is genotoxic and mutagenic.

Sustained turnover increases the probability that altered hepatocytes will expand.

Inflammation

ROS / genotoxic stress

Mutation accumulation

Slide 55 · NF-κB permits survival under genotoxic stress

NF-κB activation as a key molecular event.

Its antiapoptotic effects allow proliferating hepatocytes to survive damage.

Survival plus regeneration favors accumulation of genetic changes.

NF-κB activation

Apoptosis suppressed

Damaged hepatocytes persist

Slide 56 · HBV integration is not a universal insertion-site mechanism

HBV DNA can integrate into human chromosomal DNA.

No consistent single integration site in HCC.

Insertion can nevertheless produce structural chromosomal changes affecting cancer genes.

HBV DNA integration

Chromosomal rearrangement

Oncogene / suppressor dysregulation

Slide 57 · HBx provides an additional direct viral contribution

HBV encodes the HBx protein.

HBx can activate transcription factors and signal-transduction pathways.

These effects supplement, rather than replace, inflammation-mediated injury.

Chronic liver injury

HBx pathway activation

Combined pro-oncogenic effects

Slide 58 · HCV-associated HCC occurs without viral DNA integration

HCV has an RNA genome and is not among the five DNA viruses.

Chronic injury and compensatory regeneration remain central.

HCV core protein may also activate growth-promoting signaling; Mechanism remains uncertain.

HCV-associated chronic injury

Regeneration / oxidative stress

Possible HCV core effects

Slide 59 · The viral hepatocarcinogenesis cycle

Hepatocyte injury recruits and activates inflammatory responses.

Inflammation increases regeneration while adding mutagenic stress.

The resulting altered cells can be positively selected during repeated injury.

Chronic viral injury

Immune inflammation

Regeneration + ROS

Genomic changes

Repeated injury selects altered hepatocytes

Slide 60 · HBV, HPV and EBV use integration differently

Virus

Viral genome state

Oncogenic inference

High-risk HPV

Episomal in benign warts; integrated in many cancers

E2 disruption → increased E6/E7

EBV

Extrachromosomal circular episome during B-cell latency

Latent proteins hijack growth/survival signals

HBV

Integration possible; no consistent insertion site

Chronic injury dominant; integration/HBx also contribute

Slide 61 · HHV8 links Kaposi sarcoma to viral oncogenesis

HHV8 is also called Kaposi sarcoma-associated herpesvirus (KSHV).

Robbins finds HHV8 in virtually all Kaposi sarcoma lesions.

Viral infection is necessary but not sufficient; Immune and cellular cofactors matter.

HHV8 infection

Immune / cellular cofactors

Kaposi sarcoma

Slide 62 · Lytic and latent programs both promote Kaposi sarcoma

Lytic infection recruits inflammatory cells and local growth signals.

Latent viral proteins favor proliferation and resistance to apoptosis.

These complementary programs help create the angioproliferative lesion.

Lytic: Inflammation / VEGF

Latent: Growth / survival

Slide 63 · HHV8 encodes cell-cycle and survival modulators

A viral cyclin D homologue.

Viral proteins can inhibit p53-mediated tumor suppression.

The effects make infected spindle-cell populations more likely to persist.

Viral cyclin D homologue

P53 inhibition

Cell-cycle advantage

Slide 64 · Kaposi sarcoma is a vascular–inflammatory proliferation

Lesions contain spindle-shaped cells and slit-like vascular spaces.

Chronic inflammatory cells are intermingled with the lesion.

The microscopic pattern reflects angiogenesis and tumor–microenvironment interactions.

Spindle-cell profiles

Slit-like spaces

Inflammatory cells (small circles)

Schematic — not a histologic specimen

Slide 65 · Altered T-cell immunity is a critical cofactor

HHV8 infection alone generally does not cause Kaposi sarcoma.

AIDS-related immune suppression facilitates HHV8 persistence and dissemination.

Aging-related decline in T-cell immunity is relevant in some non-HIV cases.

HHV8 infection

Reduced immune control

Tumor-permissive milieu

Slide 66 · HHV8 is also linked to B-cell disorders

HHV8 with primary effusion lymphoma.

Multicentric Castleman disease is another linked B-cell lymphoproliferation.

A single virus can participate in endothelial and lymphoid pathology.

Kaposi sarcoma

Primary effusion lymphoma

Multicentric Castleman disease

Slide 67 · Merkel cell carcinoma has two pathogenetic settings

MCV-related tumors are emphasized in immunosuppressed patients.

Virus-independent tumors occur in sun-exposed older patients.

These pathways can converge on a similar aggressive neuroendocrine skin cancer.

MCV-associated route

UV-associated route

Slide 68 · MCV-associated Merkel cell carcinoma integrates viral DNA

In MCV-associated tumors, viral DNA is integrated into the tumor genome.

Relatively few acquired mutations and usually diploid genomes.

Viral oncoproteins influence key host growth-control pathways.

Integrated MCV

Viral oncogenic proteins

Low mutation-burden tumor

Slide 69 · MCV proteins perturb tumor-suppressive networks

Effects involving RB, p53, PP2A, and MYC.

These pathways regulate cell-cycle entry, survival, or growth.

Viral oncoprotein expression can substitute for some host genomic lesions.

MCV viral proteins

RB / p53 / PP2A / MYC networks

Growth-control disruption

Slide 70 · UV-associated tumors have a different genomic profile

Virus-independent tumors can carry many UV-signature mutations.

Acquired RB and TP53 loss-of-function changes are often present.

Copy-number gains and losses contrast with the usually diploid MCV-related group.

UV DNA injury

RB / TP53 mutations

High genomic alteration burden

Slide 71 · Immune surveillance explains rarity despite exposure

MCV infection is widespread, but Merkel cell carcinoma is rare.

Protective MCV-specific T-cell responses.

Immunosuppression shifts the balance toward MCV-associated cancer.

Frequent viral exposure

T-cell surveillance

Rare cancer in intact immunity

Slide 72 · Morphology and clinical course remain important

Merkel cell carcinoma often presents as a rapidly enlarging skin nodule.

Microscopically it resembles an aggressive neuroendocrine carcinoma.

Regional lymph-node spread is common; The viral and UV pathways differ biologically.

Rapidly growing cutaneous nodule

Neuroendocrine carcinoma morphology

Regional nodal spread

Slide 73 · Comparison of the five oncogenic DNA viruses

DNA virus

Principal cell or tissue

Illustrative malignancy

Pathogenic route

HPV

Squamous epithelium

Cervical carcinoma

E6/E7

EBV

B cells; epithelium

Burkitt / nasopharyngeal

Latent signaling / cofactors

HBV

Hepatocytes

Hepatocellular carcinoma

Inflammation ± HBx

HHV8

Vascular / B cells

Kaposi sarcoma

Angiogenesis / immune

MCV

Skin

Merkel cell carcinoma

Viral oncoproteins

Slide 74 · Direct viral oncoproteins versus tissue-injury carcinogenesis

HPV E6/E7 directly impair p53 and RB checkpoints.

EBV and HHV8 use latent growth/survival programs under immune selection.

HBV-associated HCC prominently involves chronic inflammatory injury and regeneration.

Tumor suppressor antagonism

Latent cell survival

Inflammation / regeneration

Slide 75 · Interpret viral detection in the correct context

A tumor-associated virus may be causal, a cofactor, or simply present in a host.

Clonal viral genome patterns provide evidence about timing of infection.

Mechanistic inference requires tumor type, host immunity, and additional lesions.

Virus detection

Viral activity + clonality

Tumor / host context

Slide 76 · Clinical challenge: Tumor biology and host context

A patient receiving transplant immunosuppression develops an EBV-positive B-cell mass.

Another patient has HPV-associated cervical dysplasia with HIV coinfection.

Compare how impaired T-cell surveillance changes progression risk in each case.

EBV: Uncontrolled B-cell expansion

HPV: Persistent epithelial infection

Slide 77 · Five mechanism-to-disease pairings

HPV E6/E7 → impaired p53 and RB pathways → squamous carcinomas.

EBV B-cell latency plus MYC dysregulation → Burkitt lymphoma.

HBV/HCV chronic liver injury → hepatocellular carcinoma.

HHV8 vascular growth programs → Kaposi sarcoma; MCV oncoproteins → Merkel cell carcinoma.

Viral growth signal

Host / genetic collaborator

Specific tumor phenotype

Slide 78 · Conceptual checkpoints

Which two viral proteins target p53 and RB, and what is the consequence?

Why do EBV-linked Burkitt lymphoma and post-transplant lymphoma arise by different routes?

How can HBV and HCV both drive hepatocellular carcinoma despite different genomes?

What distinguishes MCV-associated from UV-associated Merkel cell carcinoma?

Viral protein mechanism

Host immune context

Tissue injury and genomic collaboration