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HPV Related Skin Diseases and Clinical FAQs

09/30/2019

Human papillomavirus (HPV) is a small type of DNA virus that mainly infects the skin and mucous membranes (such as the anal genitalia, oral cavity, nasal cavity, pharynx, and larynx mucosa), causing benign and malignant lesions of various skin mucosa. About 5% of cancers worldwide are associated with HPV infection. Among them, cervical cancer is a typical malignant tumor caused by HPV. There are about 550,000 new cases each year, including about 288,000 deaths. Especially in developing countries, the mortality rate of female cervical cancer patients is 50 times higher than that of developed countries. In recent years, more and more studies have shown that HPV infection is closely related to the occurrence of head and neck squamous cell carcinoma, especially oropharyngeal squamous cell car-cinoma (OPSCC). It is expected that the incidence of HPV-related OPSCC in 2020 will be Higher than cervical cancer. The current pathogenic characteristics of HPV and clinical common problems are summarized below.

1. Typing and infection process of HPV

HPV classification and infection process HPV family is huge, and its classification methods are also different. According to the biological behavior of HPV, it is divided into low-risk type and high-risk type. Low-risk HPV mainly causes mucosal hyperplasia, and high-risk type is associated with the occurrence of cervical cancer and oropharyngeal cancer. According to the homology of gene sequences, HPV is divided into 16 genera such as α, β and γ. Among them, α-HPV is more studied, and its subtype can cause cervical cancer, anal genital warts and skin spasm; β- There are 25 subtypes of HPV, which are closely related to the occurrence of non-melanoma skin cancer. With the increasing incidence of β-HPV, the research of β-HPV has become a research hotspot. Literature reports and author studies have confirmed that the detection rate of β-HPV, especially HPV38 subtype, in skin squamous cell carcinoma and solar keratoderma lesions is much higher than that of the control group. It is believed that HPV38 is likely to cause skin squamous cell carcinoma. “High-risk subtype” of solar keratosis. There are few reports on subtypes such as HPVγ, δ and ε, and the relationship with human diseases remains to be further studied. In addition to classification according to the genus, depending on the clinical manifestations and the infection site of the virus, HPV is also divided into mucosa type, sputum-related type and skin type. Mucosal HPV mainly refers to HPV associated with anal genitalia and oropharyngeal mucosa. The HPV has a high degree of tissue specificity, and different subtypes are susceptible to different infection sites and cause corresponding diseases.疣Related HPV refers to HPV associated with skin such as common warts, flat warts, and warts, including some low-risk α-HPV; skin-type HPV is β-HPV, the earliest known sputum-like epidermal dysplasia-related human nipple The epiviruses (epidermodysplasia verruciformis-as-sociated HPVs, EV-HPV) are closely related to the occurrence of non-melanoma skin cancer as described above. HPV infection has a high degree of epithelial characteristics, selectively infecting skin and mucosal epithelial cells. Skin or mucosal damage is the initiation condition of HPV infection, and the gene is encoded and replicated after virus invasion. There are 8 kinds of HPV-encoded gene proteins, 6 early genes (E), which are responsible for virus replication, transcription and regulation. The late genes (L) are responsible for the coding of viral capsid proteins. Viral infection of basal cells, integration with host cells is an important factor leading to persistent viral infection.

2. Related diseases of HPV

HPV can cause a variety of benign and malignant changes after infection of the skin and mucous membranes. The skin lesions of different HPV types are also different.

2.1 HPV related benign changes

2.1.1 Skin paralysis

Infections associated with HPV, such as HPV 1, 2, 3, 4, 27, 57, 41, can cause benign skin spasms. Common warts, flat warts, and warts are the most common skin blemishes. The incidence rate is as high as 33% in children and adolescents. The rash occurs on the face, hands and soles. It is a round papule with a keratinized surface. Hyperplasia. In people with normal immunity, the course of skin spasm is self-limiting, and the rash can resolve without leaving traces.

Epidermodysplasia verruci-formis (EV) is a rare hereditary skin disease that is particularly susceptible to β-HPV, particularly HPV 5 and 8. Most of the rashes are flat and sable, symmetrically distributed, and can be spread throughout the body. Due to the large number of rashes, the current treatment is still difficult. About half of the patients can eventually develop into squamous cell carcinoma of the skin, especially the exposed parts of the skin, suggesting that the progression of EV is progressing. May be related to long-term exposure to ultraviolet light.

2.1.2 Benign mucosa

Condyloma acuminata occurs in sexually active people aged 15 to 30 years. It is one of the most common sexually transmitted diseases. It mainly occurs in internal and external genitalia, perianal, pubic, rectum (generally below the dentate line), typical lesions. It is a cockroach-like creature with a red, tan or skin tone. HPV types 6 and 11 are the most common subtypes that cause condyloma acuminata. The treatment of genital warts is mainly to remove the corpus callosum, but it is easy to relapse. Standardizing the correct use of condoms and reducing the number of sexual partners is an effective means to reduce the risk of HPV infection and transmission. As people’s sexuality is more open, the incidence of vaginal-oral-anal and other sexual behaviors increases, and the incidence of condyloma acuminata other than genital mucosa such as anal fistula, oropharynx, throat, conjunctival fistula, and nasal cavity is also increased. Is rising.

2.2 HPV related malignant changes

2.2.1 HPV and cervical cancer

Cervical cancer occurs in young women between the ages of 30 and 50. HPV infection is the main cause of cervical malignant transformation. HPV 16 and 18 have the highest detection rate in cervical cancer specimens. Some studies have found that HPV18 is more carcinogenic than HPV16. HPV16 is closely related to cervical squamous cell carcinoma, and HPV18 is more likely to cause cervical adenocarcinoma. Mixed infection of multiple high-risk HPV increases the risk of persistent infection.

2.2.2 HPV-related head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma is the sixth most common cancer in the world, including oral cancer, laryngeal cancer, and pharyngeal cancer. In the past, the bad habits of smoking and alcohol abuse were the main causes of squamous cell carcinoma of the head and neck. There is now evidence that HPV infection is closely related to its pathogenesis, especially the occurrence of pharyngeal squamous cell carcinoma. Martel et al analyzed 85,000 cases of new oropharyngeal squamous cell carcinoma. The HPV positive rate was about 25.6%, of which male patients accounted for 75.0%. Steinau et al.’s statistical analysis of HPV infection and typing of oropharyngeal squamous cell carcinoma showed that persistent infection of high-risk HPV 16 and 18 is the major subtype of precancerous lesions and squamous cell carcinoma.

2.2.3 HPV and non-melanoma skin cancer

Non-melanoma skin cancers include squamous cell carcinoma of the skin, basal cell carcinoma, solar keratosis, keratoacanthoma, etc., which are closely related to β-HPV infection. The detection rate of HPV in non-melanoma skin cancer is highest in kidney transplant patients, followed by sun exposure, which is the lowest in the general population. Although the exact mechanism is still unclear, it is currently believed that HPV may be associated with immunosuppression and ultraviolet radiation.

3. HPV and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs, and young women are prone to develop. More studies in recent years have shown that HPV infection is more common in the SLE population. Santana et al.’s analysis of 33 articles found that the risk of intraepithelial neoplasia and precancerous lesions in the cervix of patients with SLE was 9 times higher than that of the normal population, but this phenomenon is not supported by epidemiological data. Which subtype of HPV is more susceptible to infection, whether these SLE patients with cervical precancerous lesions develop cervical cancer or not, are still to be further studied. HPV detection and significance HPV testing includes the detection of DNA, RNA and HPV-specific markers, mainly for the examination of HPV infection of the cervix. There are more than 100 reported detection methods, but only four kinds approved by the FDA for clinical use: Hybrid capture second-generation test (HC2) high-risk HPV-DNA test, Cervista high-risk HPV test, Cobas 4800 test, Ap-tima HPV Detection. These four methods have their own characteristics, mainly for the screening of cervical cancer. HPV detection not only helps stratified management and monitoring of cervical intraepithelial neoplasia, atypical squamous cell carcinoma, cervical cancer, but also combined with cervical cytology screening technology to diagnose cervical cancer early and reduce death. rate.

4. Vaccine and prevention of HPV

HPV vaccine is effective in preventing HPV infection. There are currently three HPV vaccines that prevent HPV infection, one is the bivalent cervarix vaccine, which is mainly for type 16 and type 18 HPV infections; the other is the tetravalent gardasil cervical cancer vaccine. It can prevent HPV infection of 6,11,16 and 18; the nine-valent vaccine is based on the former two and adds five subtypes, namely HPV31, 33, 45, 52 and 58. Among them, the four-valent, nine-valent garda-sil vaccine can not only prevent cervical cancer, but also prevent the occurrence of genital warts by preventing HPV6 and 11 infection. The clinical application of HPV preventive vaccine in foreign countries has been more than ten years. In July 2016, the two-valent vaccine, Cheric, has been approved for listing in China.

In addition to HPV preventive vaccines, the current prevention of genital warts is achieved by standardizing the use of condoms and reducing sexual partners; non-melanoma skin cancer can reduce the incidence by reducing ultraviolet radiation.

5. Frequently FAQs of HPV

5.1 What are the ways of HPV infection?

It is currently believed that whether it is genital warts or skin blemishes, HPV is mainly transmitted through contact, especially skin mucosa with slight damage is easily infected. Genital warts are mainly transmitted through sexual behavior. The Chinese research team recently conducted HPV tests on 2,087 healthy people. The results showed that the HPV detection rate was as high as 79.92%, α-HPV was 27.07%, and β-HPV was 38.76%. The study also analyzed risk factors for HPV infection, such as sexual behavior, number of sexual partners, migrant workers, frequency of bathing, etc., and considered that sexual transmission is still an important way of HPV infection, other modes of transmission such as towels, toilets, sun exposure, etc. and HPV. The relationship between infections is not yet clear. Therefore, the prevention of HPV infection focuses on the popularization of condom applications, reducing the number of sexual partners, rather than excessive caution on daily necessities.

5.2 Can blood tests detect HPV infection?

Usually blood test to check the virus is most often detected by a certain component of the virus or by the virus to stimulate the body’s antibodies. At present, HPV is considered not to enter the blood and does not cause viremia. Therefore, blood tests are not found in the blood test; because HPV has more than 100 subtypes, studies have reported that a large number of subtypes of low titers can be detected in the blood. HPV antibodies, but the clinical significance of detecting these antibodies is still unclear, does not mean whether it is sick, not to mention the need for treatment, there is currently no kit that can be used for clinical detection of HPV antibodies, so the blood test to diagnose HPV infection is There is no scientific basis.

5.3 Need to check HPV for skin vulgaris, flat warts, sputum, etc?

These sputum are skin-type HPV infections, usually low-risk HPV, which differ from the mucosal HPV subtype that infects the cervix and causes cervical cancer. Currently approved HPV test kits are all for detecting mucosa-associated HPV. There is no kit for detecting skin sputum. The consensus is that low-risk HPV does not require virus detection. Mucosal and cutaneous HPV gene homology is different. Detection of skin sputum with a reagent for detecting mucosal HPV can lead to false negative results. Therefore, skin vulgaris, flat warts, warts, etc. do not need to check HPV, and the current method of detecting mucosal HPV is not accurate.

5.4 How to detect HPV correctly?

It is currently believed that HPV only invades mucosal epithelial cells and skin keratinocytes, and HPV requires infection to the basal cells in order to continue infection and cause disease, so the correct method is to scrape off the epidermal detection of suspicious infections. It is not correct to take only secretions or surface scales.

5.5 Is HPV positive for treatment?

Most HPV infections can be automatically cleared by the body’s immune system within a few months to 2 years, also known as “transient infection.” Sustained infection of HPV is an important factor leading to cancer. It is generally believed that HPV can continue to be infected if the same high-risk HPV is detected twice in a row for more than one year. When the cervical HPV test is positive and the tissue cytology test is negative, it does not indicate the presence of the lesion, which may usually be the carrying state of HPV. At present, HPV testing is mainly to screen high-risk HPV. If it is low-risk HPV-positive, there is no rash, and there is no need for treatment. If the same type of high-risk HPV test is positive, it needs to be combined with cytological examination, regular review, and once the histological abnormality is found, the corresponding treatment measures are taken. Because there is no effective anti-HPV drug at present, it is not recommended to treat HPV virus carrying status abroad.

5.6 Don’t worry about cervical cancer if you get a vaccine?

66% of cervical cancer is associated with HPV 16 and 18, and existing HPV vaccines are mainly for the prevention of high-risk HPV 16 and 18, and cannot prevent all high-risk HPV. Therefore, even if HPV vaccine is given, regular cervical cancer screening is needed. .

5.7 How is the HPV vaccine vaccinated?

The current HPV vaccine is a preventive vaccine and has no therapeutic effect on those who have been infected with HPV. The vaccinated population is preferably a person who has not been infected with HPV before sexual maturity. The 2015 US guidelines recommend that women who are vaccinated with HPV are 11 to 12 years old and can be vaccinated as early as 9 years old. Unmarried women and married women between the ages of 13 and 26 can benefit from the best vaccination age, so they should accept Vaccine. The 4 and 9-valent vaccines can be used in men. The recommended age is 11 to 12 years old. Men aged 13 to 21 years old, especially male homosexuals and HIV-positive men, should also be vaccinated. The vaccination of the HPV vaccine is divided into three injections within six months, and the same brand of vaccine should be used three times.

6. Conclusion of HPV

HPV infection in the human population is very common, and there is a certain detection rate in normal human skin, but HPV infection is usually transient and can be cleared by itself. Currently recognized HPV 16 and 18 are high-risk subtypes of HPV type 6 and type 11 that cause cervical cancer, which is a common type of condyloma acuminata. The approved vaccine is also mainly to prevent these two diseases. Other high-risk subtypes of HPV-related malignant tumors such as head and neck cancer, especially oropharyngeal cancer, are still under investigation. In recent years, the incidence rate has been increasing and should be paid full attention. The HPV classification is complex, and the existing HPV detection is mainly used to detect a limited number of high-risk HPV subtypes, and skin sputum caused by low-risk HPV does not need to detect HPV. HPV preventive vaccine has been approved for marketing in China. In March 2016, American scientists announced that they have completed the first phase clinical trial of HPV therapeutic vaccine. With the deepening of understanding of the pathogenesis of HPV, the disease caused by HPV is expected to be effectively controlled. treatment.

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