Herpes and HPV

• Herpesviruses


  • Large enveloped viruses
  • Contain icosadeltahedral capsid
  • Contain double stranded DNA genome
• Herpesvirus subfamilies


  • Alphaherpesviruses (HSV-1, HSV-2, VZV)
  • Betaherpesviruses (CMV, HHV-6, HHV-7)
  • Gammaherpesviruses (EBV, HHV-8)
• Latent infection


  Persistent infection following primary infection
• Reactivation


  More likely to take place during periods of Immunosuppression
• Both primary infection and reactivation are likely to be more serious in immuno-compromised patients
• HSV-1


  Cold sore
• HSV-2


  Genital herpes
• HSV-1 & HSV-2 pathogenesis

  1. Primary infection - HSV infects mucoepithelial cells, short-lived viraemia

  2. Virus disseminated in body, spread to trigeminal ganglia (HSV-1) and sacral ganglia (HSV-2)

  3. HSV1/2 establishes latency in neurons

  4. Reactivation - many triggers can provoke a recurrence
• Triggers for HSV reactivation

  • Physical or psychological stress
  • Infection
  • Fever
  • Irradiation, including sunlight
  • Menstruation
• Spread by direct contacts, most common from a kiss given to a child or adult from a person shedding the virus
• Primary infection is usually trivial or subclinical in most individuals, mainly in those below 5 years
• There are 2 peaks of incidence, the first at 0-5 years and the second in the late teens, when sexual activity commences
• Following primary infection, 45% of orally infected individuals and 60% of patients with genital herpes will experience recurrences
• The actual frequency of recurrences varies widely between individuals, the mean number of episodes per year is about 1.6
• Acute Gingivostomatitis-HSV1


  The commonest manifestation of primary herpetic infection, with pain and bleeding of the gums, and 1-8 mm ulcers with necrotic bases, self limiting disease which lasts around 13 days
• Herpes labialis (cold sore)-HSV1

  A recurrence of oral HSV, with a prodrome of tingling, warmth or itching at the site, followed by redness, papules and vesicles, 45% of orally infected individuals will experience reactivation
• Ocular Herpes-HSV1


  Herpes simplex eye infections, caused by HSV-1, typically contracted by touching a cold sore and then touching the eyes, can infect the cornea causing inflammation, eye redness, tearing
• Herpetic whitlow-HSV1


  A painful infection of the finger caused by the herpes virus, extremely contagious, with vesicles that form a crust after about 2 weeks
• Herpes Simplex Encephalitis-HSV1


  The most serious complication, with rapid onset of fever, headache, seizures, focal neurologic signs, and impaired consciousness, without treatment has a mortality rate of about 70%, treated with supportive care and intravenous antiviral therapy
• Genital Herpes: HSV2


  Genital lesions may be primary, recurrent or initial, involving the penis, vagina, cervix, anus, vulva, bladder, the sacral nerve routes, the spinal and the meninges, prone to secondary bacterial infection, 60% of patients will experience recurrences
• Neonatal herpes simplex-HSV2


  Rare, mainly the baby is infected perinatally during passage through the birth canal, the risk is higher during primary maternal infection, can cause a mild disease localized to the skin or a fatal disseminated infection, particularly dangerous in premature infants, where the brain is involved the prognosis is particularly severe, a large proportion of survivors have residual disabilities, acyclovir should be promptly given, prevention is by offering caesarean section to mothers with florid genital HSV lesions
• Laboratory diagnosis of HSV

  • Direct detection: Immunofluorescence of skin scrappings, PCR for HSV encephalitis
  • Virus isolation: Takes 1-5 days
  • Serology: Not useful in acute phase as antibodies take 1-2 weeks to appear
• Management of HSV 1/2 infections

  • Acyclovir: Drug of choice, available in IV, oral, and cream formulations
  • Other older agents: idoxuridine, trifluorothymidine, Vidarabine (ara-A)
• STI


  Sexually Transmitted Infection: Transmitted through sexual contact, may cause disease elsewhere in the body. Includes STDs.
• STD


  Sexually Transmitted Disease: Infection has progressed to cause disease
• A million people acquire an STI every day
• A majority of STIs are asymptomatic
• 500 million people get ill from 4 major STIs every year: chlamydia, gonorrhoea, syphilis & trichomoniasis
• 500 M people have HSV 2 (genital herpes) globally
• 600 M people have HPV (causes warts & cancers)
• Long term effects of STIs

  • Genitourinary tract complications - infertility, ectopic pregnancy, etc.
  • Malignancy – Genitourinary, oropharyngeal, Liver
  • Chronic/lifelong infection
  • Vertical transmission
  • Increased risk for HIV
  • Disease in other organs - CNS, liver
  • Psychological effects/Stigma
• Etiology of STIs


  • Bacterial - e.g. N. gonorrheae, T. pallidum, etc.
  • Parasitic - T. vaginalis, pubic lice, scabies
  • Viral: Human Immunodeficiency virus (HIV), Human papillomavirus (HPV), Human herpes viruses (HHVS), Hepatitis B virus (HBV), Hepatitis C virus, Some viral hemorrhagic fevers (e.g. Zika, Ebola)
• Portals of transmission for STIs

  • Oral
  • Vaginal/Penile
  • Anal
  • Direct Skin to skin contact
• High risk modes of transmission for STIs

  • Sexual intercourse: Anal, vaginal, oral
  • Blood & blood products (unscreened)
  • Vertical transmission
  • Sharing needles (PWIDS - People who inject drugs)
  • Tattooing & body piercing
• No risk or low risk modes of transmission for STIs

  • Abstinence
  • Hugging
  • Kissing
  • Sharing cutlery
  • Sitting on toilets
• Viral STIs


  e.g. HIV, HPV, HSV, HBV. No cure for most, Medication for symptoms only. Can be passed to others for the rest of your life.
• Bacterial STIs


  Gonorrhea, Syphilis, Chlamydia, LGV, Chancroid. Can be cured with antibiotics. If untreated, can cause Pelvic Inflammatory Disease, scarring, infertility, etc.
• Human papillomaviruses (HPV)


  Family: Papillomaviridae. Small (8 kBp), circular dsDNA virus. Non-enveloped. Over 200 genotypes so far, About 40 genotypes affect anogenital region. Some genotypes are linked to anogenital, oropharyngeal cancers.
• Classification of HPV


  • ICTV classification: genera, species, genotypes
  • Viral Tropism: Cutaneous (cause skin/plantar/palmar warts), Mucosal (cause anogenital or oropharyngeal warts)
  • Risk: High risk genotypes (HPV 16, 18, 33, 58, etc. associated with malignancies), Low risk genotypes (Associated with warts)
• Cervical Cancer Pathogenesis


  1. Infection by HPV

  2. Virus DNA Capsid protein

  3. HPV DNA integrated into tumour cell DNA

  4. Viral replication

  5. Invasive cancer