STI I

Question 1

HPV strains causing cervical cancer

Answer 1

16, 18

Question 2

HPV pathogenesis

Answer 2

Infect and replicate in the squamous epithelium of skin (warts) and mucous membranes (genital, oral, and conjunctival papillomas)

Infection induces epithelial proliferation

Question 3

HPV epidemiology and transmission

Answer 3

• 15-44 year old individuals are most likely to be infected
• Can be acquired via:
– Abrasions in the skin or mucosa during sexual intercourse*
– Fomites (ie., towels)*
– Infected birth canal (infant infection)*

Question 4

HPV clinical manifestations

Answer 4

Anogenital Warts
Buschke-Lowenstein tumours
Cervical Intraepithelial Neoplasia (CIN)
Penile Intraepithelial Neoplasia (PIN)
Vulvar Intraepithelial Neoplasia (VIN)
Vaginal Intraepithelial Neoplasia (VAIN)
Anal cancer

Question 5

HPV anogenital warts

Answer 5

• 70-75% of patients are asymptomatic; some experience itching, burning, and pain.
• Flesh to grey coloured hyperkeratotic, exophytic papules may be sessile or attached on a short, broad peduncle
• Individual or multiple lesions (may coalesce) to form plaques

Question 6

HPV anogenital warts in males

Answer 6

• Uncircumcised: preputial cavity in 85-90% of cases
• Circumcised: penile shaft
Urethral meatus may be involved (in ~ 1-25% of patients; warts occur generally in first 3 cm of the urethra)
• Perianal warts more common in MSM
• Lesions rarely seen on scrotum, perineum, groin & pubis

Question 7

HPV anogenital warts in females

Answer 7

• Most lesions distributed over the posterior introitus
• To a lesser degree, distributed over the labia majora and minora, and the clitoris
• Common sites in order of decreasing frequency:
Perineum > vagina > anus > cervix > urethra
Aceto-whitening: 3-5% acetic acid reveals shiny white patches with irregular borders. Often seen on uterine cervix

Question 8

Hirsutoid papillomatosis

Answer 8

Clinical manifestation of human papilloma virus (HPV): ( HP is an anatomic variant of the corona ) appears as a pearly penile papule and must be differentiated from small HPV warts

Question 9

Buschke-Lowenstein tumours

Answer 9

Perianal tumour with strongly expressed infiltrating growth

Question 10

Cervical intraepithelial neoplasia

Answer 10

Infection of the female genital tract by HPV types 16,18, 31, and 45 (and rarely by other HPV types) is associated with intraepithelial cervical neoplasia and cancer*

Question 11

HPV laboratory diagnosis

Answer 11

• HPV does not grow in cell culture
• HPV antibodies (research only)
• Papanicolaou test (Pap smears)*
• HPV DNA molecular probes and PCR from cervical swabs and tissue* specimens
• Screen for other STIs*

Question 12

HPV treatment

Answer 12

10-20% spontaneously resolve in 3-4 months*
• Treatment options include:
– Cryotherapy (liquid nitrogen)
– Surgical ablation
– Podophyllin (podofilox) (not in pregnancy)
– Other therapeutic compounds like: (5- fluorouracil; trichloracetic acid)

No option is particularly effective; many have side effects

Question 13

HPV prevention

Answer 13

Gardasil
– Comprised of L1: the major capsid protein
– Assembled into virus like particles from HPV-6,11,16,18
• 6,11 cause 80% of genital warts
• 16, 18 cause 70% of cervical cancer
– 3 Intra-muscular injections @ 0, 2 and 6 months
– Girls between 12-13 years; Free (school vaccine)
– Approved for Australian males 9-15 (school boys)`
– Women 18-26: available from GP (must pay)

Question 14

HSV virus characteristics

Answer 14

At the DNA level, HSV-1 and HSV-2 share ~50%

sequence homology, and infections caused by these viruses are clinically indistinguishable

Question 15

HSV epidemiology and transmission

Answer 15

• Infected persons are a lifelong source of contagion
• Transmitted in vesicle fluids, saliva, and vaginal secretions*
Both HSV-1 and HSV-2 can cause oral and genital lesions
– HSV-1 mainly spread by oral contact
– HSV-2 mainly spread via sexual contact; and from infected mother to infant during birth
– HSV2- frequency of infection is highest between the
ages 14 to 44 (consistently higher in women than men)
• HSV is the most common cause of genital ulcers in
Australia
• Marked degree of “crossover” today: incidence of genital HSV-1 approaching that of HSV-2*

Question 16

HSV pathogenesis

Answer 16

Both viruses infect and replicate in mucoepithelial cells, and then are able to establish infection in neurons, before being transported to the ganglion (trigeminal ganglia [oral], and sacral ganglia [genital])*

Question 17

HSV clinical manifestations

Answer 17

• After 2-5 days of incubation, primary infection moderately
severe (more severe in women) of ~3 weeks duration.
• Symptoms and signs often include:
– Fever
– Dysuria (ie., pain on urination)
– Widespread ulceration
– Inguinal lymphadenopathy (see diagram)
– General malaise and pain

Question 18

HSV in men

Answer 18

• Lesions (clear vesicles) develop on the glans or shaft of the
penis (rarely the urethra)
• Anal/perianal lesions most common in MSM (but increasingly
being seen in heterosexual men)

Question 19

HSV in women

Answer 19

• Lesion appearance associated with itching and vaginal discharge
• Lesions appear on the vulva, vagina, cervix, perianal area/or inner thigh*

Question 20

Recurrent genital herpes clinical presentation

Answer 20

– Reactivation of latent HSV in the sacral ganglion
– More likely to recur if caused by HSV-2 than HSV-1
– Usually also preceded by tenderness, itching, burning, pain
– Often lesions recur at site of primary infection; less lesions and less severe than primary infection
– Recurrences can be every 2-3 weeks (or infrequent) and are more severe in women

Question 21

HSV complications

Answer 21

HSV Encephalitis
HSV meningitis
HSV keratitis
Neonatal Infections

Question 22

HSV encephalitis

Answer 22

• Occurs at all ages (but is uncommon)
• Usually caused by HSV-1 (adults) and HSV-2 (neonatal):
generally localised to one of the temporal lobes
• Characterised by presence of red blood cells (RBC’s) in the cerebrospinal fluid (CSF)
• Associated with seizures, and focal neurologic abnormalities
• Associated with significant morbidity and mortality even with treatment

Question 23

HSV meningitis

Answer 23

Complication of genital HSV-2 infections; spontaneous resolution

Question 24

HSV keratitis

Answer 24

Usually associated with HSV-1, affecting the cornea, causing pain, redness, blurred vision, tearing, discharge, sensitivity to light; and even blindness if cornea severely scarred

Question 25

HSV neonatal infections

Answer 25

• Caused most often (70%) by HSV-2
• 1 in 13 000 births in Australia
• More likely to occur after birth through infected birth
canal (infected mother with asymptomatic shedding
of virus)
• Manifestations range from disease localised to skin,
eyes and mouth, to disseminated disease (liver,
lungs, and CNS involvement)*
• Prevention via caesarian birth or antiviral therapy at time of delivery*

Question 26

HSV diagnosis

Answer 26

Tzanck or Papanicolaou (PAP) test for irregular cell types – Tzanck test shows “giant” multinucleated cells with
inclusion bodies (Cowdry type A)

Cell culture (to show cytopathic effects (CPE)
• Swab of lesion, or samples of cerebrospinal fluid (CSF) processed via PCR (distinguishes between HSV-1 and HSV-2)

Serology
– HSV-type specific IgM can be detected in acute infections
– Serology often only used for epidemiological studies