Human papillomavirus infection

Introduction

Introduction to human papillomavirus infection The English name of papovaviridae is derived from papillomavirus, polyomavirus and similar vacuoulolating virus, which includes papillomavirus and Two genera of polyomavirus, all of which are tumorigenic DNA viruses. basic knowledge The proportion of illness: 0.01%-0.03% Susceptible people: no special people Mode of transmission: contact with sexually transmitted mother-to-child transmission Complications: Condyloma acuminata

Cause

Cause of human papillomavirus infection

Virus infection (30%):

HPV is primarily transmitted through contact with infected areas or contaminated items.

Sexual transmission (35%):

Genital infections are mainly transmitted by sexual intercourse, and the life cycle of new papillomavirus is closely related to epidermal cell differentiation.

Mother-to-child transmission (35%):

Newborns can be infected in the birth canal. Viral infections are often localized and spread without blood flow. Different types of HPV can cause papilloma in different parts. Skin sputum is generally benign. HPV DNA is free, and some cockroaches can Regression, high-risk human papillomavirus is closely related to genital precancerous lesions and malignant tumors. HPV DNA is often integrated into the chromosomes of host cells.

The damage caused by HPV is affected by immune factors, cell-mediated immunity is more important, skin sputum appears after HPV infection, and will resolve spontaneously after a long time; the incidence of cervical cancer in immunosuppressed patients will increase.

Pathogenesis

HPV is transmitted directly or indirectly to the host skin and mucosal epithelial cells, enters the cell through the contact of the tiny erosion surface, and replicates and transcribes in the epithelial nucleus of the infected site, but does not enter the blood circulation, and does not produce viremia. After replication and assembly, the virus particles first accumulate in the nucleus, then release, and gradually infect neighboring cells, so that more and more host cells are infected by HPV, which becomes a source of self-inoculation and transmission, and the viral DNA can be integrated. In the host cell DNA, the cell DNA is synchronously replicated, causing all the daughter cells of the infected cell to be in a latent infection state. In the latent infection period, the virus exists as a plasmid or an episomal gene that is self-replicating. These genomes can also infect adjacent cells. .

Prevention

Human papillomavirus infection prevention

There is currently no effective prevention method, the most important of which is:

1. Do not touch the lesions of this disease.

2. Prevent the exudate with HPV from polluting the public environment, and clean and disinfect the bathtub, bath towel and toilet.

3. Patients with anal and external genital warts should be diagnosed and treated first. Men should use condoms during sexual intercourse to prevent genital HPV infection.

4. Strengthen public health knowledge and sexual education, focus on strengthening moral education for people with sexual disorders, and clean themselves.

5. Vaccine-related HPV vaccines are under development. Promising vaccines are: multivalent structural protein vaccines, non-protein-binding vaccines, E6, E7 protein vaccines and peptide vaccines.

Complication

Human papillomavirus infection complications Complications Condyloma acuminata

Generally no special complications.

Symptom

Symptoms of human papillomavirus infection Common symptoms Porphyra rash wet joints nodular hemorrhagic keratitis hoarse squamous cell carcinoma airway obstruction asphyxia

After the infection, the incubation period is as short as 6 weeks and the longest is 2 years. HPV infection can be divided into mucosal surface infection and skin infection, but the difference is not absolute. The clinical manifestations are various, and the infection can be asymptomatic. Or produce perceptible benign sputum, or recurrent episodes of gradual growth and difficult to treat pathological damage, and some can be converted to invasive tumors. Common clinical manifestations are as follows:

1. There are three main types of skin moles.

(1) : verruca plantaris occurs in the common sputum of the foot, and more infringes on young people and adults. Trauma and friction may be the cause of the disease, and there is a certain relationship between the sweating of the foot and the occurrence of sputum. At the beginning, it is a horny horny horn that gradually enlarges to a pale yellow or yellowish brown plaque with a diameter of 2mm to 1cm or more. The surface is keratinized, rough and uneven, grayish brown, grayish yellow or dirty gray. , round, clear boundary, central dimple, the edge is surrounded by a slightly higher horny ring, scraping the surface of the stratum corneum, you can see the angular boundary between the corner layer and the sputum, the center can see punctiform bleeding, occur in the heel The compression of the humeral head or toe, sometimes occurring on the base of the iliac crest, usually on one side, the number is variable, sometimes several small satellite rafts can appear around a large corpus callosum, or they can gather together or Blended into a horny plaque, such as with a knife to remove keratinous plaque, visible several horny soft core, especially known as mosaic warts (mosaic warts), can have obvious tenderness, the course of the disease is chronic, can naturally fade.

(2) Common warts: Verruca vulgaris is clear, highlights the skin, is highly keratinized, has a rough surface, is hard and solid, has a taupe or normal skin tone, and starts to be a tip-sized papule that gradually expands to the bowl. Large or larger, continue to develop papillary hyperplasia, no inflammation around, mostly single at the beginning, can be unchanged for a long time, but also gradually increased to several or dozens due to self-inoculation, sometimes several damages Confluence into tablets, generally no symptoms, occasional tenderness, easy to bleed when rubbed or impacted, occurs in the back of the hand, fingers, feet, nail edge, etc., the latter is called periungual warts, there is tenderness, It is easy to cause rupture and infection, but it can also occur in the palm and sole of the foot, but it rarely occurs in the mucosa.

The special types of common warts are:

1 filamentous sputum (filiform warts), occurs in the neck, eyelids, forehead, etc., often single hair, the corpus callosum is slender filamentous protrusions, apical keratinization, generally no symptoms, if it occurs in the eyelids, Conjunctivitis or keratitis.

2 digitate warts (digitate warts), also seen in the scalp, also seen in the face, between the toes, the surface of the carcass is jagged finger-like protrusions, the tip of which is keratin-like material, the number varies.

(3) Flat warts: verruca plana, also known as young flat warts, mainly invades adolescents, most of which appear suddenly, from rice grains to soybeans, round, oval or polygonal, flat and slightly protruding pimples , the surface is smooth, hard, light brown or normal skin tone, the number is more, most dense, even can be arranged along the distribution of scratches into strips, generally no symptoms, occasionally itchy, bleeding, pain (when the surface is stressed or When rubbed), but rarely see the carcinogenesis of sputum, occurs in the face, neck, forearm and back of the hand, sometimes accompanied by common warts, laryngeal papilloma, chronic disease, self-resolving, but also after several years The more you get, the more scars you leave, the more you can relapse.

2. Genital wart (genital wart), also known as condyloma accuminatum (venereal warts), is a benign neoplasm of skin mucosa caused by HPV, mainly transmitted through sexual contact, mostly in young people, men and women All are susceptible, the lesion usually grows at the junction of mucous membrane and skin. The virus replicates in the nucleus of susceptible cells, causing cell proliferation. The disease can naturally regress, but it can recur. In recent years, some cases have been found to develop cervical cancer. This has caused widespread attention.

The incubation period varies from 1 to 8 months, with an average of 3 months, and there are dominant infections, subclinical infections and latent infections.

(1) Dominant infection: visible obvious scorpion mites, flesh-colored to gray, highly keratinized, attached to the skin, more commonly attached to a soft wide pedicle, lesions from smooth, pearl-like to the edge is not Neat, uneven surface, overlapping each other, shaped like papillary, braided, cauliflower-like and cockscomb-like, soft texture, easy to hemorrhage, wet surface, ranging from less than 1mm to 2cm, can be merged into large clumps, Prone to erosion, exudate with stench, etc., good hair: male hair in the glans, coronary sulcus, the inside of the foreskin, foreskin ligament, urethra and penis, homosexuals occur in the perianal and rectal, female More often in the size of the labia, vagina, perineum, cervix, perianal, anorectal, urethra and even groin and other parts of the genitals, a small number of tiny reddish papules at the initial onset, gradually increase and increase, the surface is often due to friction and rupture and secondary Infection, often asymptomatic at the beginning, followed by rash, pain, burning sensation in the affected area, increased vaginal discharge in female patients, even bloody vaginal discharge, milky odor discharge, and gonorrhea, trichomoniasis, true At the same time, the number or size of lesions during pregnancy will increase, which will affect the delivery, often reduce or disappear after delivery, 1% to 25% of patients with urethral damage, in the inverted urethra or endoscopy, clearly visible, but the disease The damage will not go deep into the urethra 3cm away. The bladder and its proximal urethra are generally harmless. The lesions around the anus in homosexual patients are much higher than those in heterosexual patients. Most genital warts can resolve on their own, but they are not treated. It can be extended, repeated, and a few may be malignant.

(2) Subclinical infection: In recent years, due to increased infection of HPV-16 and HPV-18, subclinical infections have increased, and lesions can affect penis, vulva, vagina, cervix, urethra and bladder, anus and anus. More sessile, flat, small, vaginal lesions are rough micro-nipples (nodular) of the epithelial bulge concentrated on the capillary sputum, called spiked condyloma, and the other is no Uplifted flat lesions, ie nonspecified intraepithelial neoplasia, male patients with epidermal fistula on the penis, protruding from the foreskin and scrotum surface, small diameter, can be as large as 1cm, round, A brown to dark blue peduncle, distributed in the male and female vulva, and even invaded the anus, rectum, urethra, etc.

(3) latent infection: asymptomatic and no visible lesions. Detection of HPV DNA by nucleic acid hybridization or PCR can confirm the diagnosis. It is also reported that HPV infection in normal women can be as high as 70%, and can be detected in normal neonatal foreskin. This virus.

Gay people are most prone to perianal fistula, and 2/3 patients have both anal external anus and anal internal paralysis.

Recent studies have shown that genital warts in the vagina, penis or perianal area can be converted into squamous cell carcinoma, and the transformation time usually takes 5 to 10 years. It has been reported that 4.7% to 10.0% of cervical condyloma acuminata, 5% vulva and Perianal condyloma acuminata, after a long-term incubation, can develop into metastasis, carcinoma in situ and invasive carcinoma. Using nucleic acid hybridization method, HPV-6 and HPV in genital warts are found in biopsy materials of some invasive cancers. Type 11 DNA-related sequence, giant condyloma acuminata is a kind of squamous cell carcinoma, which usually occurs on the male glans foreskin. The damage can penetrate deep into the genital tract, and many fistulas lead to the urethra, and then the pus is drained from the fistula. Urine.

3. Respiratory papilloma Respiratory papilloma is a benign tumor, mainly found in young children, can occur in the throat, laryngeal papilloma grows rapidly, the lesion develops rapidly, seriously affects ventilation, and there is hoarseness and croup. Surgical resection is performed in time to avoid suffocation. The lesion often spreads to the trachea or lungs. It also causes airway obstruction. When the lung is further infected with secondary infection, it is prone to respiratory distress. In adults, it is easy to turn into cancer. The respiratory papilloma is caused by Caused by HPV-6 and HPV-11.

4. Verrucous epidermal dysplasia Epidemic dysplasia (epidermodysplasia verruciformis, EV) is a rare lifelong skin disease that occurs in infants or children, characterized by intractability, transmission, and flattening Skin lesions, or skin spots of different colors, EV is a multifactorial disease, in addition to specific HPV infection, but also genetic, immune and other internal factors, some people think that EV is an epithelial Congenital defects, some people think that EV is a special form of systemic spasm.

5. Bowen papulosis (BP) and Bowen disease. Barren papulosis is a multifocal benign rash-like lesion with histological features of carcinoma in situ, but with strong clinical manifestations. Part of it is benign. The difference between BP and Bowen's disease is that BP is multifocal and often occurs in the anus, genital and foot skin. The patient is younger (average 26 years old), and the patients with Bowen's disease are mostly Over the age of 50, the pathogen of BP has been unclear for many years. Some people extracted DNA from 12 BP biopsy tissues and hybridized with HPV-11 and HPV-16. All tissues were found to hybridize with HPV-16. In addition, HPV- 6 genomics were also found in BP, suggesting that HPV may be a BP pathogen, HPV-16 and other types of HPV (HPV-5, HPV-8) were detected in patients with Bowen's disease, suggesting that Bowen's disease may also be associated with Related to HPV.

Examine

Examination of human papillomavirus infection

1. Electron microscopy HPV is one of the first viruses observed under electron microscope. Negative staining of biopsy specimens can be diagnosed if characteristic viral particles can be seen under electron microscope. Immunoelectron microscopy can improve detection rate. Although the accuracy of electron microscopy is very high, it takes time and requires special equipment and the detection rate is very low.

2. PCR technology can detect HPV-DNA by this method, and can also perform genotyping with sensitivity up to 1fg. This method is simple and time-saving, and the source of the specimen is not limited, such as diseased tissue or exfoliated cells, secretions or mucus. Fresh specimens or specimens of long-lasting paraffin sections can be used.

3. Serological examination Currently, the diagnosis and classification of HPV can not be performed by serological method. For the development-specific serological test, the advanced protein produced by the genetic engineering expression is being studied to detect the corresponding antibody in the serum of the patient. The L1 and L12 proteins can be used to detect HPV type specific immune responses.

4. Nucleic Acid Hybridization Technology Nucleic acid molecular hybridization technology can not only diagnose HPV, but also HPV, and use radionuclide or biomarker HPV-DNA probe to detect the presence of complementary nucleic acid strands in patient specimens. The most common method is dot blot hybridization followed by Southern blotting and in situ hybridization.

5. Endoscopy should be found in the vagina, anus and rectum, urethra and other parts of the genital warts are required to use endoscopy, such as colposcopy, colonoscopy and urethraoscopy, according to the appearance of the characteristics of the diagnosis.

After the host cell is infected, the virus continues to proliferate and produce local lesions, causing excessive proliferation of the skin surface layer, but the histopathological damage characteristics are different, which is related to the type of HPV, the number and the infection site and the immune status of the body, for example: HPV-16 Compared with HPV-18 and HPV-6, HPV-6 and HPV-11 are more likely to cause invasive tumors in the lower vagina; although papillary tumors are benign, they can be life-threatening due to obstruction of the respiratory tract, and pregnant women and immunocompromised people are more seriously infected. The squamous epithelium of the cervical cell transition zone is particularly sensitive to the tumorigenic effects of HPV. Some cells show structural changes in typical papilloma cells. Some cells are transformed into characteristic acantic cell vacuolization, granular layer, The clear layer cells are keratinized.

Diagnosis

Diagnosis and diagnosis of human papillomavirus infection

Diagnostic criteria

1. Epidemiological data have direct or indirect contact with HPV-infected or HPV-contaminated items.

2. Clinical manifestations According to the clinical manifestations of various sputum, it is not difficult to diagnose this sputum. Various skin sputum and genital warts can be diagnosed by visual observation. However, a large number of human populations have discovered: genital lesions and tissues observed by the naked eye. About 10% of the results of the examinations did not match and further examination was needed.

3. Auxiliary inspection

(1) Nucleic acid molecule hybridization detection HPV-DNA and serological methods for detection of HPV antigen.

(2) Histopathological examination: the smear of the hairy part, the smear of the secretion, the biopsy of the lesion, and the diagnosis according to the characteristic histological and histopathological damage.

Differential diagnosis

1. Sickle skin tuberculosis needs to be differentiated from common warts, but it is irregular plaque, surrounded by redness, often accompanied by symptoms of tuberculosis.

2. The corns need to be differentiated from the cockroaches, the tenderness is obvious, and the surface is smooth.

3. Hair follicle epithelial tumors and syringomas sometimes need to be differentiated from flat warts, which occur near the eyes and have completely different histological changes.

4. Papilloma is larger than condyloma acuminata, some diameters can reach 4 ~ 8cm, the course of disease is slow, often asymptomatic, mostly in elderly women, need to be sent to pathological examination to confirm the diagnosis.

5. The second stage syphilis flat wart is mostly single, with clear edges, neat, flat and clean base, hard and painless hard squat, syphilis serum reaction can be used as a basis for diagnosis.

6. Genital squamous cell carcinoma is more common in people over 40 years old. There is no history of unclean sexual intercourse, and the infiltration damage is obvious. It often forms ulcers. Histopathological examination can confirm the diagnosis.

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