Questions

Human papillomavirus — Questions

Study questions about Human papillomavirus — exam-style, clinical-scenario and FAQ.

Mock Exam mode

Sit this set one question at a time. Multiple-choice questions mark themselves; written questions reveal a tickable mark scheme so you can score your own answer. You get a combined score at the end.

17 questions: 12 MCQ, 5 written.

High-priority (past-paper) questions only

Low-risk HPV 6 and 11 cause the great majority of anogenital warts (condylomata acuminata). They are not premalignant but recur often.

HPV 16 and 18 are the high-risk oncogenic types, 31 and 33 other high-risk mucosal types, and 5 and 8 cutaneous beta types.

HPV gene expression is coupled to epithelial differentiation. Late genes (L1 and L2) are expressed and virions assembled only in the most superficial, differentiating keratinocytes, which is why the virus could not be grown in conventional monolayer culture.

The basal layer maintains only the silent episome; there is no viraemia, no lymphocyte infection, and no separate latency programme.

HPV-positive oropharyngeal cancer, driven mainly by HPV16, carries a markedly better prognosis than the tobacco-related HPV-negative cancers. It is rising in high-income countries, arises in the tonsil and tongue base, and uses p16 immunostaining as its surrogate marker.

It is not caused by the low-risk types 6 and 11, its incidence is increasing rather than falling, and p16 positivity is central to its diagnosis.

Human immunodeficiency virus (HIV) impairs the cell-mediated immunity that clears HPV, so people living with HIV clear the virus poorly, carry multiple high-risk types and progress to cancer faster. This is why they undergo more intensive cervical screening.

Clearance is slower, not faster, the natural history is clearly affected, infection is not confined to low-risk types, and there is no protective effect.

E2 normally represses the E6/E7 promoter; when integration of viral DNA disrupts the E2 gene, that repression is lost and E6 and E7 are expressed without restraint. This is the molecular switch from productive infection to transformation.

E6 and E7 then degrade p53 and inactivate the retinoblastoma protein, but E2 loss itself acts by derepression, not by degrading p53 directly or by any role in entry, capsid formation or virion assembly.

The major capsid protein L1 self-assembles into virus-like particles (VLPs) that mimic the capsid surface and raise neutralising antibody while containing no viral DNA. This is the molecular basis of the prophylactic HPV vaccines.

L2 is the minor capsid protein; E6 and E7 are the oncoproteins; E2 controls viral transcription.

E6: recruits a cellular ubiquitin ligase to degrade p53, removing the G1 DNA-damage checkpoint and apoptosis, so damaged cells are not eliminated.

E7: binds and inactivates the retinoblastoma protein (Rb), releasing the E2F transcription factors and driving the cell from G1 into S phase unchecked.

Point in the cycle: both act at the G1/S transition, E6 removing the checkpoint brake while E7 forces entry.

Net effect: continuous, deregulated proliferation with genomic instability, and, where a high-risk type persists and integrates, progression to immortalisation and malignant transformation.

A complete answer covers the taxonomy, how types are defined, and the clinical risk grouping.

Family and genera

HPV belongs to the family Papillomaviridae. More than 450 human types fall into five genera: Alphapapillomavirus (mucosal and some cutaneous, containing the oncogenic types), Betapapillomavirus (cutaneous, linked to skin cancer in epidermodysplasia verruciformis), Gammapapillomavirus, Mupapillomavirus and Nupapillomavirus (cutaneous).

How types are defined

A type differs by more than 10% in its L1 gene sequence from the nearest known type; smaller differences define subtypes and variants. Classification is genetic because the virus could not be cultured and raises little cross-reacting antibody.

High-risk versus low-risk

High-risk mucosal types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) encode E6 and E7 proteins that inactivate p53 and the retinoblastoma protein and cause cancer; HPV16 and 18 cause most cervical cancer. Low-risk types (chiefly 6 and 11) cause anogenital warts and respiratory papillomatosis but not cancer.

A complete answer follows the virus up through the epithelium and links each phase to the differentiation state.

Infection and maintenance

The virus reaches dividing basal keratinocytes only through a microabrasion, binding heparan sulphate then a secondary receptor. The genome enters the nucleus during mitosis and is maintained as a low-copy episome by E1 and E2, held quiet so little viral protein is made: a near-silent reservoir.

Productive phase tied to differentiation

Productive replication begins only as infected cells leave the basal layer and differentiate. Because differentiated cells have left the cell cycle, E6 and E7 re-drive it and recruit the host replication machinery; the genome amplifies, and L1 and L2 are expressed with virion assembly only in the most superficial cells. E4 weakens the cornified layer so virions shed passively in squames, with no lysis and no viraemia.

Why culture is hard

Because the full cycle requires a stratified, differentiating epithelium, the virus cannot complete replication in ordinary monolayer culture; propagation needed organotypic raft cultures or xenografts, which is why HPV was characterised genetically rather than by isolation.

A complete answer traces infection, persistence, integration, and the action of the E6 and E7 oncoproteins.

From infection to persistence

HPV infects the basal keratinocytes of the cervical transformation zone through a microabrasion. Most infections are productive and cleared within about two years; malignant risk arises only when a high-risk type persists.

Integration and loss of E2

Progression is associated with integration of viral DNA into the host genome, which typically disrupts the E2 gene. Because E2 represses the early promoter, its loss derepresses the E6 and E7 oncogenes, which are then overexpressed.

E6 and E7 drive transformation

E6 recruits the E6-AP ubiquitin ligase to degrade p53, disabling apoptosis and the DNA-damage response. E7 binds and inactivates the retinoblastoma protein (Rb), releasing E2F and forcing cell-cycle entry. Together they cause genomic instability and aneuploidy, and persistent expression drives graded cervical intraepithelial neoplasia (CIN) to invasive carcinoma over years to decades.

Epidermodysplasia verruciformis (EV) is an inherited inability to control beta papillomaviruses; HPV 5 and 8 are found in most of the sun-exposed cutaneous squamous cell carcinomas that result.

The high-risk alpha mucosal types drive anogenital and oropharyngeal cancers instead, and the low-risk 6 and 11 cause warts.

Roughly 90% of new HPV infections become undetectable within two years, about half within nine months. Only a persistent minority, mostly high-risk types, carries the risk of progression to cancer.

Clearance within a week or a month is far too fast, and persistence beyond five to ten years is the exception rather than the rule.

The low-risk types 6 and 11 that cause anogenital warts also cause recurrent respiratory papillomatosis, the juvenile form acquired perinatally from maternal genital infection.

HPV 16 and 18 are high-risk oncogenic types, 5 and 8 are cutaneous beta types, and 31 and 45 are other high-risk mucosal types.

HPV has a small circular double-stranded DNA genome of about 8 kilobases (kb), with all genes on one strand: early genes (E1, E2, E4, E5, E6, E7), late genes (L1, L2) and a non-coding regulatory region.

It is not an RNA virus and does not reverse-transcribe; a partially double-stranded, reverse-transcribing genome describes hepatitis B virus.

Gardasil 9 covers HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58; its seven oncogenic types account for about 90% of cervical cancers.

The bivalent and quadrivalent vaccines (types 16 and 18) cover close to 70%, so the nonavalent gain is real but not total.

The koilocyte, a squamous cell with a perinuclear halo and an enlarged, irregular nucleus, is the morphological signature of productive HPV infection.

Owl-eye inclusions are cytomegalovirus, Negri bodies are rabies, Downey cells are the reactive lymphocytes of infectious mononucleosis, and multinucleated syncytia point to herpes simplex or measles.

A complete answer spans the benign and malignant ends and notes the rising entities.

Benign disease

Cutaneous warts (common, plantar and flat, mostly HPV 1, 2, 27 and 57); anogenital warts (condylomata acuminata, HPV 6 and 11), the commonest clinical HPV disease; and recurrent respiratory papillomatosis (HPV 6 and 11), bimodal with a perinatally acquired juvenile form.

Inherited susceptibility

Epidermodysplasia verruciformis, an inherited inability to control beta HPV, causes widespread warts and cutaneous squamous cell carcinoma on sun-exposed skin.

Malignant disease

Persistent high-risk infection causes intraepithelial neoplasia and cancer of the cervix, vulva, vagina, penis and anus, each preceded by a gradable precancerous phase. Anal cancer is rising in men who have sex with men and people living with HIV, and HPV-positive oropharyngeal cancer is a distinct, rising and better-prognosis entity driven by HPV16.

High priorityMCQ
Anogenital warts (condylomata acuminata) are caused mainly by which HPV types?
- A. HPV 6 and 11
- B. HPV 16 and 18
- C. HPV 31 and 33
- D. HPV 5 and 8
- E. HPV 1 and 2
Show answer
Correct answer: A
Low-risk HPV 6 and 11 cause the great majority of anogenital warts (condylomata acuminata). They are not premalignant but recur often.

HPV 16 and 18 are the high-risk oncogenic types, 31 and 33 other high-risk mucosal types, and 5 and 8 cutaneous beta types.
High priorityMCQ
HPV late (L1 and L2) gene expression and virion assembly occur where?
- A. In the basal keratinocyte layer
- B. In circulating blood
- C. Only during viral latency
- D. In differentiating suprabasal cells
- E. In circulating infected lymphocytes
Show answer
Correct answer: D
HPV gene expression is coupled to epithelial differentiation. Late genes (L1 and L2) are expressed and virions assembled only in the most superficial, differentiating keratinocytes, which is why the virus could not be grown in conventional monolayer culture.

The basal layer maintains only the silent episome; there is no viraemia, no lymphocyte infection, and no separate latency programme.
High priorityMCQ
HPV-positive oropharyngeal cancer is characteristically which of the following?
- A. Better prognosis than HPV-negative disease
- B. Caused by HPV 6 and 11
- C. Falling in incidence
- D. Unrelated to p16 status
- E. Worse prognosis than smoking-related disease
Show answer
Correct answer: A
HPV-positive oropharyngeal cancer, driven mainly by HPV16, carries a markedly better prognosis than the tobacco-related HPV-negative cancers. It is rising in high-income countries, arises in the tonsil and tongue base, and uses p16 immunostaining as its surrogate marker.

It is not caused by the low-risk types 6 and 11, its incidence is increasing rather than falling, and p16 positivity is central to its diagnosis.
High priorityMCQ
In people living with HIV, HPV infection characteristically shows which pattern?
- A. Reduced clearance, faster cancer progression
- B. Faster clearance than in HIV-negative people
- C. No effect on the natural history
- D. Infection by low-risk types only
- E. Protection against cervical cancer
Show answer
Correct answer: A
Human immunodeficiency virus (HIV) impairs the cell-mediated immunity that clears HPV, so people living with HIV clear the virus poorly, carry multiple high-risk types and progress to cancer faster. This is why they undergo more intensive cervical screening.

Clearance is slower, not faster, the natural history is clearly affected, infection is not confined to low-risk types, and there is no protective effect.
High priorityMCQ
Loss of the HPV E2 gene when viral DNA integrates promotes cancer by which mechanism?
- A. Directly degrading the p53 protein
- B. Encoding the viral capsid proteins
- C. Derepressing the E6/E7 promoter
- D. Blocking viral entry into cells
- E. Assembling progeny virion particles
Show answer
Correct answer: C
E2 normally represses the E6/E7 promoter; when integration of viral DNA disrupts the E2 gene, that repression is lost and E6 and E7 are expressed without restraint. This is the molecular switch from productive infection to transformation.

E6 and E7 then degrade p53 and inactivate the retinoblastoma protein, but E2 loss itself acts by derepression, not by degrading p53 directly or by any role in entry, capsid formation or virion assembly.
High priorityMCQ
Which HPV protein self-assembles into the virus-like particles used in the vaccines?
- A. E6
- B. L1
- C. L2
- D. E7
- E. E2
Show answer
Correct answer: B
The major capsid protein L1 self-assembles into virus-like particles (VLPs) that mimic the capsid surface and raise neutralising antibody while containing no viral DNA. This is the molecular basis of the prophylactic HPV vaccines.

L2 is the minor capsid protein; E6 and E7 are the oncoproteins; E2 controls viral transcription.
High prioritySAQBriefly discuss the oncogenesis of HPV, with specific mention of the mechanism of action of E6 and E7 and the point in the cell cycle affected. [5]
Model answer
E6: recruits a cellular ubiquitin ligase to degrade p53, removing the G1 DNA-damage checkpoint and apoptosis, so damaged cells are not eliminated.

E7: binds and inactivates the retinoblastoma protein (Rb), releasing the E2F transcription factors and driving the cell from G1 into S phase unchecked.

Point in the cycle: both act at the G1/S transition, E6 removing the checkpoint brake while E7 forces entry.

Net effect: continuous, deregulated proliferation with genomic instability, and, where a high-risk type persists and integrates, progression to immortalisation and malignant transformation.
High priorityExam-styleClassify the human papillomaviruses and explain the basis of the high-risk versus low-risk distinction. [6]
Model answer
A complete answer covers the taxonomy, how types are defined, and the clinical risk grouping.

Family and genera

HPV belongs to the family Papillomaviridae. More than 450 human types fall into five genera: Alphapapillomavirus (mucosal and some cutaneous, containing the oncogenic types), Betapapillomavirus (cutaneous, linked to skin cancer in epidermodysplasia verruciformis), Gammapapillomavirus, Mupapillomavirus and Nupapillomavirus (cutaneous).

How types are defined

A type differs by more than 10% in its L1 gene sequence from the nearest known type; smaller differences define subtypes and variants. Classification is genetic because the virus could not be cultured and raises little cross-reacting antibody.

High-risk versus low-risk

High-risk mucosal types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) encode E6 and E7 proteins that inactivate p53 and the retinoblastoma protein and cause cancer; HPV16 and 18 cause most cervical cancer. Low-risk types (chiefly 6 and 11) cause anogenital warts and respiratory papillomatosis but not cancer.
High priorityExam-styleDescribe how the HPV replication cycle is coupled to keratinocyte differentiation, and why this made the virus difficult to culture. [6]
Model answer
A complete answer follows the virus up through the epithelium and links each phase to the differentiation state.

Infection and maintenance

The virus reaches dividing basal keratinocytes only through a microabrasion, binding heparan sulphate then a secondary receptor. The genome enters the nucleus during mitosis and is maintained as a low-copy episome by E1 and E2, held quiet so little viral protein is made: a near-silent reservoir.

Productive phase tied to differentiation

Productive replication begins only as infected cells leave the basal layer and differentiate. Because differentiated cells have left the cell cycle, E6 and E7 re-drive it and recruit the host replication machinery; the genome amplifies, and L1 and L2 are expressed with virion assembly only in the most superficial cells. E4 weakens the cornified layer so virions shed passively in squames, with no lysis and no viraemia.

Why culture is hard

Because the full cycle requires a stratified, differentiating epithelium, the virus cannot complete replication in ordinary monolayer culture; propagation needed organotypic raft cultures or xenografts, which is why HPV was characterised genetically rather than by isolation.
High priorityExam-styleDescribe the pathogenesis of human papillomavirus infection leading to malignant transformation. [6]
Model answer
A complete answer traces infection, persistence, integration, and the action of the E6 and E7 oncoproteins.

From infection to persistence

HPV infects the basal keratinocytes of the cervical transformation zone through a microabrasion. Most infections are productive and cleared within about two years; malignant risk arises only when a high-risk type persists.

Integration and loss of E2

Progression is associated with integration of viral DNA into the host genome, which typically disrupts the E2 gene. Because E2 represses the early promoter, its loss derepresses the E6 and E7 oncogenes, which are then overexpressed.

E6 and E7 drive transformation

E6 recruits the E6-AP ubiquitin ligase to degrade p53, disabling apoptosis and the DNA-damage response. E7 binds and inactivates the retinoblastoma protein (Rb), releasing E2F and forcing cell-cycle entry. Together they cause genomic instability and aneuploidy, and persistent expression drives graded cervical intraepithelial neoplasia (CIN) to invasive carcinoma over years to decades.
MCQ
Epidermodysplasia verruciformis predisposes to cutaneous squamous cell carcinoma through which HPV?
- A. High-risk alpha mucosal types
- B. Mucosal types 16 and 18
- C. Low-risk types 6 and 11
- D. Gamma wart types
- E. Beta types 5 and 8
Show answer
Correct answer: E
Epidermodysplasia verruciformis (EV) is an inherited inability to control beta papillomaviruses; HPV 5 and 8 are found in most of the sun-exposed cutaneous squamous cell carcinomas that result.

The high-risk alpha mucosal types drive anogenital and oropharyngeal cancers instead, and the low-risk 6 and 11 cause warts.
MCQ
Most incident HPV infections become undetectable within roughly what period?
- A. One week
- B. One month
- C. Two years
- D. Five years
- E. Ten years
Show answer
Correct answer: C
Roughly 90% of new HPV infections become undetectable within two years, about half within nine months. Only a persistent minority, mostly high-risk types, carries the risk of progression to cancer.

Clearance within a week or a month is far too fast, and persistence beyond five to ten years is the exception rather than the rule.
MCQ
Recurrent respiratory papillomatosis is caused by which HPV types?
- A. HPV 16 and 18
- B. HPV 5 and 8
- C. HPV 31 and 45
- D. HPV 6 and 11
- E. HPV 2 and 27
Show answer
Correct answer: D
The low-risk types 6 and 11 that cause anogenital warts also cause recurrent respiratory papillomatosis, the juvenile form acquired perinatally from maternal genital infection.

HPV 16 and 18 are high-risk oncogenic types, 5 and 8 are cutaneous beta types, and 31 and 45 are other high-risk mucosal types.
MCQ
The HPV genome is best described as which of the following?
- A. Linear single-stranded RNA
- B. Segmented RNA
- C. Linear double-stranded DNA
- D. Partially reverse-transcribing DNA
- E. Circular double-stranded DNA
Show answer
Correct answer: E
HPV has a small circular double-stranded DNA genome of about 8 kilobases (kb), with all genes on one strand: early genes (E1, E2, E4, E5, E6, E7), late genes (L1, L2) and a non-coding regulatory region.

It is not an RNA virus and does not reverse-transcribe; a partially double-stranded, reverse-transcribing genome describes hepatitis B virus.
MCQ
The nonavalent HPV vaccine covers the types behind approximately what share of cervical cancer?
- A. ~50%
- B. ~90%
- C. ~30%
- D. Essentially all
- E. ~70%
Show answer
Correct answer: B
Gardasil 9 covers HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58; its seven oncogenic types account for about 90% of cervical cancers.

The bivalent and quadrivalent vaccines (types 16 and 18) cover close to 70%, so the nonavalent gain is real but not total.
MCQ
What is the cytological hallmark of productive HPV infection on a cervical smear?
- A. A multinucleated syncytium
- B. The koilocyte
- C. The Downey cell
- D. An owl-eye inclusion
- E. The Negri body
Show answer
Correct answer: B
The koilocyte, a squamous cell with a perinuclear halo and an enlarged, irregular nucleus, is the morphological signature of productive HPV infection.

Owl-eye inclusions are cytomegalovirus, Negri bodies are rabies, Downey cells are the reactive lymphocytes of infectious mononucleosis, and multinucleated syncytia point to herpes simplex or measles.
Exam-styleOutline the spectrum of disease caused by human papillomavirus. [6]
Model answer
A complete answer spans the benign and malignant ends and notes the rising entities.

Benign disease

Cutaneous warts (common, plantar and flat, mostly HPV 1, 2, 27 and 57); anogenital warts (condylomata acuminata, HPV 6 and 11), the commonest clinical HPV disease; and recurrent respiratory papillomatosis (HPV 6 and 11), bimodal with a perinatally acquired juvenile form.

Inherited susceptibility

Epidermodysplasia verruciformis, an inherited inability to control beta HPV, causes widespread warts and cutaneous squamous cell carcinoma on sun-exposed skin.

Malignant disease

Persistent high-risk infection causes intraepithelial neoplasia and cancer of the cervix, vulva, vagina, penis and anus, each preceded by a gradable precancerous phase. Anal cancer is rising in men who have sex with men and people living with HIV, and HPV-positive oropharyngeal cancer is a distinct, rising and better-prognosis entity driven by HPV16.