by Sean Elliott, MD

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    00:01 The papillomaviridae viruses.

    00:05 Papilloma viruses are small and nonenveloped, with an icosahedral capsid with -- and this is important to remember -- circular, double-stranded DNA genome.

    00:15 They are transmitted through direct or sexual contact with actively expressed legions, which mostly are warts.

    00:23 And the incubation period is quite prolonged from 4-21 weeks.

    00:29 Initial infection occurs at the cutaneous and mucosal epithelial surfaces, typically of genital tissue.

    00:37 And then viral proteins E6 and E7 are expressed, and these inactivate the growth suppressors in the target tissues, meaning that those same epithelial tissues hen develop hyperplasia at the basal layer.

    00:52 And anytime one has hyperplasia of lesions, then one is at risk for developing malignancy.

    01:00 To make a diagnosis of any primary lesion with a human papillomavirus, HPV, is primarily a clinical diagnosis.

    01:09 One can look at the lesions are typically flat, somewhat hypopigmented compared to underlying skin, and they occur in many different places.

    01:20 You can see an image of several warts or several lesions in the top on this slide, with arrows identifying specific hypopigmented, flat, almost pale-looking HPV warts or lesions.

    01:36 In addition, there are characteristic appearances on pathology, and one further can make diagnoses through serology and PCR.

    01:45 Pap smears, especially, will demonstrate koilocytes, which are dysplastic squamous cervical cells with a raisinoid nuclei.

    01:53 It almost sounds like a chocolate bar and it's not.

    01:55 Raisinoid nuclei with hyperchromasia.

    01:59 And on the side slide's picture to the lower right, you can see with the red arrow identify 1 such site with prominent nuclei.

    02:10 So, let's look specifically at the diseases caused by the human papillomaviruses and the types of diseases depend on what serotype we're talking about.

    02:20 This will be important when we eventually get to prevention and the vaccines which cover some, but not all of these.

    02:27 Starting then with serotypes 1-4, these human papillomaviruses all cause skin warts, such as you see in the picture of the plantar aspect of a foot.

    02:38 These are benign, as are most of the initial warts.

    02:41 Tan colored to again, hypopigmented.

    02:46 They feel soft, but they look like a flattened cauliflower.

    02:50 So, a description would be a plantar wart, cauliflower-liked, skin-colored or soft tan colored lesion, usually on the plantar aspects of the hands and feet.

    03:00 These represent epidermal hyperplasia and hyperkeratosis.

    03:06 Human papillomaviruses types 6 and 11 will cause warts as well, but localized to the anogenital side, and this is known as condylomata acuminata.

    03:16 And these, again, are benign warts with extraneous growth of squamous epithelium occurring typically in the perianal region.

    03:25 And again, a picture's worth 1000 words on the lower part of the slide.

    03:31 Type 6 and 11 also can cause laryngeal papillomas, and although these are benign and growing in laryngeal tissue, they can grow to quite extensive sizes and extensive numbers, and actually can cause airway obstruction.

    03:45 Sometimes, this has additional effects on swallowing dysfunction if there is a significant amount of tissue growth.

    03:51 So, this ends up being quite an issue for management for even otherwise healthy individuals.

    03:58 Human papillomaviruses 16 and 18 are specifically able to cause cervical intraepithelial neoplasia.

    04:06 These are the bad ones that we start to worry about and try to prevent with vaccines because they can progress to underlying carcinomas.

    04:15 You can see a picture on the lower part of the slide showing early such lesions, and this is mucosal dysplasia, looking both inflamed and also, again, that sort of paler appearing, flat-based lesion.

    04:30 So, prevention.

    04:31 Because all of these potentially can progress and certainly, are quite ubiquitous for the cutaneous lesions.

    04:39 The vaccines available are able to demonstrate or create seroprotection to specific types, and you see them listed there.

    04:47 1 vaccine product will cover types 18, 16, 6, and 11.

    04:52 Another prevents just 16 and 18.

    04:55 The major goal for these vaccines is to prevent cervical carcinoma.

    05:00 So, therefore, the people to vaccinate are those -- and it says young women, but also a target is to young men prior to reaching sexual maturity or prior to reaching sexual activity.

    05:13 The goal is to give these young adults, or children, protection against the cancer-causing human papillomaviruses before they're exposed to them through age of sexual maturity.

    05:26 So, human papillomaviruses, then, when they develop can be treated, but it's not always a successful process.

    05:35 Warts, cutaneous warts, even perianal warts can be removed, they can be scraped, they can be surgically cauterized.

    05:42 And then, the injection of interferon alpha an also reduce the activity of the human papillomavirus to prevent a recurrence.

    05:52 The laryngeal papillomas, as I noted before, are quite a significant problem if they grow to the size to cause obstruction of the larynx.

    06:00 And in those cases, surgical removal is necessary.

    06:04 However, it only removes the tissue.

    06:06 It does not treat the underlying virus.

    06:09 And so, the use of additional therapies, imiquimod and cidofovir with antiviral activity, have been tried, although their efficacy is not 100%.

    06:19 So, human papillomaviruses are ubiquitous, they're sexually transmitted.

    06:25 In the early ages of life, they are not an issue, but as one gets older and older, they become increasingly of a problem.

    06:32 Vaccines, again, is to prevent specifically the serotypes associated with cervical neoplasia and the progression to malignancy.

    About the Lecture

    The lecture Papillomaviruses by Sean Elliott, MD is from the course Viruses.

    Included Quiz Questions

    1. Circular double-stranded DNA
    2. Linear double-stranded DNA
    3. Circular double-stranded RNA
    4. Linear single-stranded DNA
    5. Linear double-stranded RNA
    1. E6 and E7
    2. E1 and E2
    3. E8 and E9
    4. E4 and E5
    5. E12 and E13
    1. Koilocytosis
    2. Lichenification
    3. Keratosis pilaris
    4. Poikilocytosis
    5. Anisocytosis
    1. 6 and 11
    2. 1 and 4
    3. 16 and 18
    4. 7 and 13
    5. 9 and 21

    Author of lecture Papillomaviruses

     Sean Elliott, MD

    Sean Elliott, MD

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