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Human papillomaviruses, or HPV for short, are a group of non-enveloped DNA viruses that
specifically infect human epithelial cells.
There are over 100 different types of HPVs which can be categorized by the epithelial
cells they prefer to infect; like cutaneous epithelial cells of the skin, especially the
face, hands and feet; and epithelial cells of mucous membranes, especially the respiratory
tract including the pharynx, and nasal and oral cavities; and anal and genital regions.
Some types can cause benign tumors, called papillomas or warts; and some can lead to
carcinomas, or cancer of the epithelial cells.
HPV may have contributed to both actor Michael Douglas’s throat cancer diagnosis, and former
first lady of Argentina, Eva Perón’s fatal cervical cancer.
Epithelial cells line the outer surfaces of organs and blood vessels and separate the
interior of the body from the external world.
They primarily serve as a protective barrier to invasion by pathogenic bacteria, fungi,
parasites and viruses; and to water loss.
In locations like the skin, anus, genitals, and respiratory tract, they can be stratified,
having more than one layer of epithelial cells.
At the base, the layer closest to the interior of the body, these cells are less mature,
rounded stem cells, also called basal cells.
Basal cells divide and replenish all the cells found in the epithelium.
As the basal cells divide and mature, they move toward the outermost layer, flattening
out and becoming more squamous shaped in appearance.
Once they reach the top layer, these mature, flat cells are exfoliated, or shed, from the
epithelium.
Now, typically basal cells are well protected under all those layers.
But if there are abrasions or cuts in the epithelium, HPV can gain access to and infect
the basal cells.
Once that happens, HPV can replicate with or without being incorporated into the basal
cell’s DNA through the activities of two particular viral genes called E6 and E7.
The proteins of these genes cause dysregulation of tightly-scheduled replication of the epithelial
cells by altering the p53 and retinoblastoma protein (pRB) tumor suppressor pathways that
typically prevent unregulated growth of the epithelial cells.
In this way, HPV causes uncontrolled replication of the epithelial cells, forming warts, and
disrupts the normal structure of the epithelium, forming lesions.
In some types of HPV infections, a squamous epithelial cell can become a koilocyte, or
a cells with an irregular shape, enlarged and dark staining nucleus, and a clear area
around the nucleus that’s called a perinuclear halo.
These cells are typical of precancerous lesions that can transform into carcinomas when the
abnormal epithelial cells break through the basement membrane of the epithelium and invade
other tissues.
The cause of an HPV infection is contact with infected epithelial cells.
Some activities can increase the risk of exposure, like having multiple or new infected sexual
partners, or delivering a baby through an infected birth canal.
And infections are more likely if a person is already immunocompromised.
Transformation to carcinomas is dependent on HPV type and aided by other cofactors like
tobacco use, immunosuppression, and radiation.
Now, many HPV infections are asymptomatic, but when symptoms are present, they can vary
by HPV type.
So, symptoms of nongenital cutaneous infections can involve some kind of benign wart.
Common skin warts of the hands or nails are typically painless, dome-shaped projections
that give the skin a rough appearance.
Plantar warts on the soles of the feet can be painful,
and scaly.
Flat warts of the face and extremities, particularly in the pediatric population, are often painless,
small, smooth, and flat-topped but numerous.
Filiform warts of the face, particularly the eyelids and lips, have long projections that
appear thread- or finger-like.
And in rare cases, where there is an underlying genetic disorder called epidermodysplasia
verruciformis, a chronic cutaneous infection can start out as flat warts and transform
into skin cancer.
Infections of mucous membranes like the upper respiratory tract, can cause respiratory papillomatosis
and can lead to voice changes and high-pitched breath sounds, particular if the larynx is
infected.
Anal and genital infections (like the female vulva, cervix and vagina; and male penis and
scrotum), can involve numerous warts called condylomata acuminata.
They tend to be skin-colored and can range in size, but have a cauliflower-like look
to their surface.
Though they are typically painless, they can cause itching, burning, local pain, or bleeding.
Now, HPV types 6 and 11 are responsible for the majority of laryngeal papillomatosis and
genital warts and are considered low-risk HPVs because they don’t tend to progress
beyond warts.
But high-risk HPV types like types 16 and 18 have a high risk of transforming into cancers
of the cervix, vagina, vulva, penis, anus, or upper respiratory tract over one or two
decades.
Warts are used to diagnosis HPV, particularly in cutaneous infections.
Infections of mucous membranes may require additional interventions to visualize epithelial
cells.
An endoscopy, a tube with a camera at the end, may be needed if an infection of the
upper respiratory tract is suspected; and regular pap or acetic acid tests of the cervix
after 21 years old are recommended even if symptoms are sub-clinical.
But a definitive diagnosis of HPV can not be made without molecular testing of biopsied
cells for viral DNA or RNA.
So treatments often center around removal of warts and precancerous lesions with salicylic
acid products, liquid nitrogen cryotherapy, or laser or surgical removal.
In cases of frequent re-occurrences, immune modifiers may be used to help boost the immune
system to remove the infection on its own.
Most HPV infections can resolve on their own over time, particularly with low-risk types
and in younger people.
But really, prophylaxis against infection, is the best course.
But limiting contact with potentially infected persons; or receiving the HPV vaccine before
first exposure to an infection source can also be protective against several strains,
including high-risk types 16 and 18.
Condom use should also be considered a measure of prevention.
So, to recap: Human papillomavirus is a DNA virus spread through contact that infects
human epithelial cells of the skin and mucous membranes.
Symptoms can range from warts, to precancerous lesions and carcinomas.
Definitive diagnosis can be made molecularly and treatment can range from allowing the
immune system to clear the infection, to mechanical or chemical removal of infected cells.