DR. GAURAV S. SALUNKHE2 N D MDS

Human Papillomavirus in the oral cavity of children

jr. of oral Path Med. 2011

What is a Virus?

It is a Latin word which means venom or poison.Exceptionally simple living microbes.They are ultramicroscopic, metabolically inert,

infectious organism.They live and multiply in living cells.Contain a single type of nucleic acid (DNA or RNA)

and a protein coat. Obligatory intracellular parasites.Range from 10 to less than 200 milimicron in length.It’s classification is based on type of nucleic acid,

strategy for replication, and morphology

HPV

The human papilloma virus is small, non-enveloped, icosahedral DNA virus of the Papillomavirida family.

Approximately 55nm in diameter.It has a circular, double stranded DNA measuring

from 7500-8000 base pairs.100 types of human papilloma virus have been

identified. In the oral cavity 24 types are associated with benign lesions.

Type1,2,3,4,6,7,10,11,13,16,18,30,31,32,33,35,45,52,55, 57,59,69,72,& 73.

And 12 are associated with malignant lesion. Type- 2,3,6,11,13,16,18,31,33,35,52,&57.

Disease HPV type

Common warts 2, 7, 22

Plantar warts 1, 2, 4, 63

Flat warts 3, 10, 8

Anogenital warts 6, 11, 42, 44 and others

Anal dysplasia (lesions) 6, 16, 18, 31, 53, 58

Genital cancers

•Highest risk: 16, 18, 31, 45•Other high-risk: 33, 35, 39, 51, 52, 56, 58, 59•Probably high-risk: 26, 53, 66, 68, 73, 82

Epidermodysplasia verruciformis more than 15 types

Focal epithelial hyperplasia (oral) 13, 32

Oral papillomas 6, 7, 11, 16, 32

Oropharyngeal cancer 16

Verrucous cyst 60

Laryngeal papillomatosis 6, 11

Papillomavirus are species specific and infect squamous epithelia and mucous membranes, inducing different types of warts or papillomata in their hosts.

The human Papillomavirus infects only humans and grow only in organ cultures of human skin.

Among the pathological entities associated with HPV in the oral cavity, are squamous papilloma, condyloma acuminatum, and focal epithelial hyperplasia.

Moreover, HPV has been also identified and correlated to the lichen planus, pemphigus vulgaris, oral squamous cell carcinoma and verrucous carcinoma.

About 30-40 types can infect the genital area-vulva, vagina, cervix, rectum, anus, penis and scrotum. Some types cause genital warts, some cause changes in cells. Most types seem to have no harmful effect at all.

Mechanism of Infection Installation

HPV uses mammalian cell to develop their cycle and replicate.

HPV has a natural propensity to infect epithelial cells, whether cutaneous or in mucosal site, and induce formation of tumors or papillomatosis to stimulate their own replication.

HPVs are capable of remaining associated with the host for long periods of time, causing persistent infection.

Because of the capacity of HPV to infect mucosal epithelial and cutaneous cells of the stratified epithelial tissue and to produce viruses as these cells differentiate, its replication cycle is know as a differentiation-dependent viral cycle.

Initial HPV infection occurs in epithelial trunk or basal cell, or in cells which are dividing transitorily, located in the lower stratified epithelium layers.

As deeper epithelium cells divide, they migrate from the basal layer and gradually differentiate.

HPV infection begins when a viral particle penetrates basal and undifferentiated cells and in epithelium division.

In basal and suprabasal cells, viral DNA undergoes replication and early genes are transcribed.

Transmission

Prenatal and Natal

Sexual contact

Hands

Blood

Shared objects

Sexual contact.The principal route for HPV is by means of sexual

contact. Such transmission may occur following a single

sexual relation with an infected partner.Condoms do not completely protect from the virus

because the areas around the genitals including the inner thigh area are not covered, thus exposing these areas to the infected person’s skin.

Transmission

Prenatal and NatalInfected pregnant woman may transmit the virus to fetus during their pregnancy or at the time of birth and among the family members. New born babies are more exposed to HPV infection during birth, when they pass the infected birth canal. Perinatal transmission of HPV

types 6 and 11 can result in the development of juvenile-onset recurrent respiratory papillomatosis. Sinal SH, Woods CR (2005). "Human papillomavirus infections of the genital and respiratory tracts in young children". Seminars in pediatric infectious diseases 16 (4): 306–16

Another possible route of transmission of the virus suggested by the literature was breast milk, regardless of the recognised and valuable benefits of breastfeeding on the child's health.

Transmission

HandsStudies have shown HPV transmission between hands and genitals of the same person and sexual partners.•Men's fingertips became positive for high risk HPV at more than half the rate as their genitals. Harris R. (2007). "The Optimal Anatomic Sites for Sampling Heterosexual Men for HPV Detection: The HPV Detection in Men Study". The Journal of Infectious Diseases 196 (8).

Shared objects•Sharing of possibly contaminated objects may transmit HPV.  Tsai, P. L.; Chang, Y. L.; Hsieh, T. T.; Jin, J. Y. (Mar

1993). "Possible non-sexual transmission of genital human papillomavirus infections in young women".European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 12 (3): 221–222.

Some authors still suggest that HPV transmission can occur through utensils used for eating food, clothes and toys or by intimate person to person contact such as kissing, although this is less frequent.

Transmission

Blood •Though it has traditionally been assumed that HPV is not transmissible via blood recent studies have called this notion into question. Historically, HPV DNA has been detected in the blood of cervical cancer patients.•Transmission through amniotic fluid should also be considered.

Common Symptoms of Genital Warts

This is transmissible and autoinoculable viral disease, present as soft pink nodules which proliferate and coalesce to form diffuse papillomatous clusters of varying size.

They occur mostly on the anogenital skin or other moist areas.

The symptoms may include single or multiple fleshy growths around the penis, scrotum, groin, vulva, vagina, anus, and/or urethra.

They may also include: itching, bleeding, or burning, and pain.

The symptoms may recur from time to time.

In males, condylomata occur earliest near the frenulum.

And are most frequent on the coronal sulcus , the shaft, and the preputial borders (the edges of the foreskin.)

Although almost all genital warts are not cancerous, large and confluent lesions should be carefully examined and multiple biopsies obtained to rule out underlying malignancies. It may be important to biopsy the darker warts to rule out the possibility of underlying skin cancer.

Some studies show that women with genital warts are at an increased risk for cancer of the cervix. Women with genital warts should have a yearly pap smear to catch any abnormalities in early stages.

Complications of Genital Warts(if untreated)

It may destroy body tissue around the genitals and anus.

For pregnant women Delivery complications or need for C-section Juvenile Onset Recurrent Respiratory Papillomatosis

(JO-RRP) in the infant.

Oral Manifestation of HPV

While human papillomavirus (HPV) is most notable for its involvement in cervical cancer, it is also commonly found in the oral cavity as well.

Oral benign HPV lesions are mostly asymptomatic and may persist or relapse spontaneously.

Common HPV-associated lesions1. Squamous papilloma.2. Verruca vulgaris.3. Focal epithelial hyperplasia.4. Condyloma acuminatum.

Oral Manifestation of HPV

Squamous papilloma. The most common benign epithelial neoplasm of oral epithelium.

squamous papilloma lesions may be found anywhere in the mouth with a predilection for the ventral tongue and frenum area, palate, and mucosal surface of the lips. 

Oral papillomas can be recognized by their small fingerlike projections, resulting in an exophytic lesion with a rough or cauliflower like verrucous surface. These lesions often have a white appearance.

Can occur in any age group.

Squamous papilloma lesions are thought to be induced by HPV 6 or 11. 

The typical treatment is surgical excision. All lesions resembling a squamous papilloma are recommended for excision at the base (1-mm margin) to the depth of the submucosa. Removal should also be considered the cure.

Recurrence or appearance of new lesions suggests the possibility of retransmission of a condyloma acuminatum or a carcinoma.

Verruca vulgaris. Also known as the common wart, verruca vulgaris the most prevalent HPV skin lesion, but it can also be found in the oral cavity. This lesion is usually associated with HPV 2 and 4.

In the mouth, verruca vulgaris is found most commonly on the keratinized surfaces of the gingiva and palate.

Verruca vulgaris lesions are contagious, and it is thought that some oral lesions occur following autoinoculation.

These lesions are typically found in children but can be seen in any age group.

Verruca vulgaris lesions often rapidly enlarge (average size <5 mm) and then remain stable, very often for several years.

Treatment is the same (surgical excision).

Focal epithelial hyperplasia. Also known as Heck disease, focal epithelial hyperplasia is associated with HPV 13 and 32 and was originally diagnosed in the Inuit population. 

Heck disease frequently affects children but is increasingly seen in the HIV-positive population as well.

This lesion is typically located in the labial, buccal, and lingual mucosa.

Focal epithelial hyperplasia lesions usually resemble the normal mucosal colour but may occasionally appear white and papillary.

Clinically, one would find multiple soft, smooth, dome-shaped papules measuring 3 mm to 10 mm and lacking a pebbly surface.

The lesions often persist for many months or even years and spontaneously resolve with no treatment. The risk of recurrence is minimal.

Condyloma acuminatum. Oral condylomas are associated with HPV 2, 6, and 11.

Clinically, these lesions are similar in appearance to papillomas but are usually larger in size and are more clustered.

Also, condylomas are known to be more diffuse and deeply rooted then papillomas. 

These lesions are most commonly found on the labial mucosa, soft palate, and lingual frenum. 

Condylomas arise through oral sex as well as by autoinoculation or as a result of maternal transmission.

Most often, condylomas in the oral cavity are related to oral-genital contact.

When these lesions are diagnosed in children, the examining clinician should be aware that their presence may be an indication of sexual abuse, and the appropriate authorities should be notified.

Condylomas can cause disfigurement and are difficult to treat.

It is best to surgically remove all of the lesions simultaneously to lessen the probability of autoinoculation.

Excision with lasers may lead to spread of the virus via airborne particles and is not advised.

Child Carcinogenesis and HPV

Cancer is a disease primarily caused by cytogenetic changes that progress through a series of sequential somatic mutations in specific genes resulting in uncontrolled cellular proliferation.

It may be caused by exposure to any one or more of a variety of chemical or physical agents, by random errors of genetic replication, or by errors in DNA repair processes.

Carcinogenesis mechanism related to HPV presence are still somewhat obscure.

It is believed that there is an integration of high risk HPV with cellular host DNA, resulting in disintegration of protein E6 and E7, which are viral protein responsible for the inactivation of the tumor suppressor genes. pRb.

The most common oncogenic viral types are 16 & 18.

Recent data demonstrate the possible relation of HPV with spinocellular carcinoma of the mouth and these represent 95% of malignant tumors affecting oral cavity.

Chow et al, evidenced the presence of HPV-DNA in two young patients with oral carcinoma.

HPV 16 & 18 which is strongly associated with cervical cancer, it can be associated with oral carcinoma.

IHC & hybridization was carried out on patients with1. Verrucous leucoplakias.2. Erythroplakias3. Homogeneous leucoplakia Who developed carcinoma during the period of 4-12

yrs were positive for HPV type 16.

Conclusion

The presence of HPV in the oral mucosa of children should be investigated in virtue of the various form of transmission, including the possibility of sexual abuse and its possible relation with oral cancer.

Vaccination could be carried out.The vaccine needs to be administered before

exposure to the virus, ideally before young people becomes sexually active.

Thank you