[ZKKL] Academic Sharing | HPV-Related Skin Diseases and Answers to Common Clinical Questions

Release time：2019-09-18

Article reprinted from: Dermatology Bulletin, Issue 01, 2017, page 96.

Authors: Xu Yanan, Ma Cuiling

[Abstract] Human papillomavirus (HPV) is a small DNA virus that primarily infects the skin and mucosal surfaces—such as the anogenital region, oral cavity, nasal cavity, pharynx, and laryngeal mucosa—leading to a range of benign and malignant lesions. Globally, approximately 5% of all cancers are attributable to HPV infection; among these, cervical cancer is a quintessential HPV‑associated malignancy, with roughly 550,000 new cases annually and about 288,000 deaths. In particular, in developing countries, the mortality rate from cervical cancer is up to 50 times higher than in developed nations. Recent studies have increasingly demonstrated a close association between HPV infection and the development of head and neck squamous cell carcinoma, especially oropharyngeal squamous cell carcinoma (OPSCC). It is projected that by 2020, the incidence of HPV‑related OPSCC will surpass that of cervical cancer. The following provides an overview of HPV’s pathogenic characteristics and common clinical issues.

[Keywords] Human papillomavirus 、 virus 、 Disease

HPV Genotyping and the Infection Process

1 HPV Typing and the Infection Process HPV The family is large, and its classification methods also vary. According to… HPV Biological behavior is classified into low-risk and high-risk types. Low-risk type HPV It primarily induces verrucous hyperplasia of the mucosa, while high-risk types are closely associated with the development of cervical cancer and oropharyngeal cancer. Based on differences in gene sequence homology, … HPV It is classified into α, β, and γ, among others. 16 A genus, among which α has been studied most extensively. -HPV , its subtypes can cause cervical cancer, anogenital warts, and cutaneous warts. ; beta -HPV There are a total of 25 A subtype closely associated with the development of non-melanoma skin cancers; as its incidence rises year by year, β -HPV Research in this area has also gradually become a research hotspot. Literature reports and the author’s own studies have confirmed β. -HPV , especially HPV38 The detection rate of this subtype in cutaneous squamous cell carcinoma and actinic keratosis lesions is significantly higher than that in the control group; it is currently believed that… HPV38 It is very likely a “high-risk subtype” that causes cutaneous squamous cell carcinoma and actinic keratosis. Regarding… HPV There are few reports on the γ, δ, and ε subtypes, and their relationship to human diseases remains to be further investigated. In addition to classification by genus, depending on the distinct clinical manifestations and the sites of viral infection, HPV It is further classified into mucosal, wart‑associated, and cutaneous types; the mucosal type… HPV Primarily refers to conditions involving the anogenital region and the oropharyngeal mucosa. HPV , these subtypes of HPV It exhibits high tissue specificity; different subtypes preferentially infect distinct anatomical sites and elicit corresponding clinical manifestations. Wart‑associated type. HPV Refers to conditions associated with skin warts, such as common warts, flat warts, and plantar warts. HPV , which includes some low-risk type α -HPV; Cutaneous type HPV That is, β -HPV , originally referred to as wart-like epidermodysplasia verruciformis-associated human papillomavirus ( epidermodysplasia verruciformis-as-sociated HPVs ， EV-HPV) As mentioned above, it is closely associated with the development of non-melanoma skin cancers. HPV The infection exhibits a strong tropism for epithelial tissues, selectively infecting epidermal and mucosal epithelial cells. Breaks in the skin or mucosa are… HPV The initiation conditions for infection involve the virus entering the host and subsequently carrying out genetic replication. HPV The encoded gene proteins total 8 Species, early genes (E) 6 Species, responsible for viral replication, transcription, and regulation ; Late gene (L) 2 It encodes the viral capsid protein. The virus infects basal epithelial cells, and its integration into the host genome is a key factor underlying persistent viral infection.

HPV-related diseases

Following infection of the skin and mucous membranes, HPV can give rise to a variety of benign and malignant lesions; different… HPV The cutaneous manifestations of type-specific infections also vary.

2. 1 HPV Related benign changes

2. 1 . 1 Skin wart Wart-associated HPV types, such as HPV1，2，3，4，27，57，41 Infections can lead to the development of benign skin warts. Common warts, flat warts, and plantar warts are the most frequent types of cutaneous warts, with an incidence as high as in children and adolescents. 33% The rash commonly affects the face, hands, and soles of the feet, presenting as round papules with warty hyperkeratotic overgrowth on the surface. In immunocompetent individuals, cutaneous warts are self‑limiting, and the lesions may resolve without leaving any residual scarring.

Epidermodysplasia verruciformis (epidermodysplasia verruci-formis, EV) It is a rare hereditary skin disorder, and patients are sensitive to β. -HPV Particularly susceptible, especially HPV5 and 8 Type. The rash typically presents as flat, wart-like lesions, symmetrically distributed and potentially widespread across the body. Due to the large number of lesions, treatment remains challenging; approximately half of patients eventually develop cutaneous squamous cell carcinoma, particularly in sun-exposed areas, suggesting… Electric Vehicle The progression of the condition may be associated with long-term exposure to ultraviolet radiation.

2. 1 . 2 Benign mucosal wart Condyloma acuminatum commonly occurs in individuals aged 15 to … 30 Among sexually active individuals, it is one of the most common sexually transmitted infections, primarily affecting the external and internal genitalia, the perianal region, the mons pubis, and the rectum. ( Generally below the dentate line. ) Typical skin lesions present as rooster-comb–like papules, with colors ranging from red to brownish‑tan or skin‑colored. HPV6 and 11 Type is the most common subtype that causes genital warts. Treatment for genital warts primarily involves removing the wart lesions, but recurrence is frequent. Using condoms correctly and consistently, and reducing the number of sexual partners, are effective strategies to lower the risk of transmission. HPV An effective means of preventing infection and transmission. As people’s attitudes toward sexuality become more open, the vagina… - Oral cavity - With the increasing prevalence of anal and other non‑vaginal sexual practices, the incidence of genital warts occurring outside the genital mucosa—such as anorectal warts, oropharyngeal warts, laryngeal warts, conjunctival warts, and nasal warts—is also steadily rising.

2. 2 HPV Related malignant changes

2. 2 . 1 HPV With cervical cancer Cervical cancer commonly occurs in women aged 30 to… 50 a young woman of years old, HPV Persistent infection is the primary cause of cervical carcinogenesis. HPV16 and 18 It was detected at the highest rate in cervical cancer specimens, and some studies suggest that… HPV18 Its carcinogenic effect is stronger than HPV16 , there are also reports HPV16 It is closely associated with cervical squamous cell carcinoma, whereas… HPV18 It more readily predisposes to the development of cervical adenocarcinoma, with multiple high-risk types. HPV Mixed infections increase 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 worldwide, encompassing oral, laryngeal, and pharyngeal cancers. Traditionally, unhealthy lifestyle factors such as smoking and excessive alcohol consumption were considered the primary causes of this malignancy; however, emerging evidence indicates that human papillomavirus (HPV) infection is closely linked to its development, particularly in cases of oropharyngeal squamous cell carcinoma. Martel Wait for... 85 000 For example, an analytical study of newly diagnosed patients with oropharyngeal squamous cell carcinoma found that... HPV The positivity rate is approximately 25 . 6% , of which male patients account for 75 . 0% 。 Steinau For squamous cell carcinoma of the oropharynx, HPV Statistical analysis of infections and genotyping indicates that high-risk types… HPV16 and 18 Persistent infection with this genotype is the predominant subtype that predisposes to the development of oropharyngeal precancerous lesions and squamous cell carcinoma.

2. 2 . 3 HPV Non-melanoma skin cancer Non-melanoma skin cancers include cutaneous squamous cell carcinoma, basal cell carcinoma, actinic keratosis, and keratoacanthoma, among others; their development is associated with β -HPV Closely related to infection. Non-melanoma skin cancer HPV The detection rate is highest among kidney transplant patients, followed by individuals with extensive sun exposure, and lowest in the general population. Although the precise underlying mechanisms remain unclear, current consensus attributes this to… HPV Pathogenesis may be associated with immunosuppression and ultraviolet irradiation.

HPV and Systemic Lupus Erythematosus

Systemic lupus erythematosus (systemic lupus erythematosus, SLE) It is a multi-organ autoimmune disease that predominantly affects young women. In recent years, numerous studies have demonstrated that… HPV Infection in SLE More commonly seen in the population. Santana Wait for... 33 An analysis of the treatise reveals that, SLE Patients have a higher risk of developing cervical intraepithelial neoplasia and precancerous lesions compared with the general population. 9 fold, but this phenomenon is not yet supported by epidemiological data. Which subtype exactly… HPV More susceptible to these precancerous cervical lesions. SLE Whether patients will progress to cervical cancer and other outcomes remains to be further investigated. 3 HPV Testing and Significance HPV Testing includes DNA , R NA and HPV Detection of specific biomarkers is primarily used for cervical infections. HPV of the examination. The reported detection methods include 100 Other species, but was FDA Approved for clinical use only 4 seed : Next-generation hybrid capture assay (HC2) High-risk type HPV-DNA Testing, Cervista High-risk type HPV Testing, Cobas 4800 Testing, Ap-tima HPV Testing. Each of these four methods has its own unique characteristics and is primarily used for cervical cancer screening, among other applications. HPV Such testing not only facilitates stratified management and surveillance of populations with cervical intraepithelial neoplasia, atypical squamous cells, and cervical cancer, but, when combined with cervical cytology screening, enables early diagnosis of cervical cancer and reduces morbidity and mortality.

HPV Vaccine and Prevention

The HPV vaccine can effectively prevent HPV Infection. Currently, there are three types. HPV Vaccines can prevent. HPV Infection—one type is the bivalent Shirek. (Cervarix) Vaccines, primarily targeting 16 Type, 18 Type HPV Infection ;

Another option is the quadrivalent Gardasil cervical cancer vaccine, which can prevent… 6，11，16 and 18 Type HPV Infection ; The 9-valent vaccine builds on the previous two by adding another 5 a subtype, namely HPV31，33，45，52 and 58 . Among them are the quadrivalent and nine-valent Gardasil vaccines. (guard-sil) Vaccines not only help prevent cervical cancer but also, by preventing… HPV6 and 11 Prevention of infection and the occurrence of genital warts. Clinical application abroad. HPV Preventive vaccines have been available for more than a decade, 2016 Year 7 The bivalent vaccine Shirek has been approved for marketing in China.

In addition to the HPV preventive vaccine, the prevention of genital warts currently relies primarily on consistent condom use and reducing the number of sexual partners. ; Non-melanoma skin cancers can be reduced in incidence by minimizing exposure to ultraviolet radiation.

Frequently Asked Questions

5 . 1 HPV What are the routes of infection? ?

At present, it is believed that whether it is genital warts or cutaneous warts, HPV It is primarily transmitted through direct contact, with even minor breaks in the skin or mucous membranes being particularly susceptible to infection. Genital warts are mainly spread through sexual activity. A Chinese research team recently conducted a study on… 2 087 Conducted on healthy individuals HPV Testing, the results show that HPV The detection rate is as high as 79 . 92 . % , α -HPV occupy 27 . 07% , β -HPV occupy 38 . 76% . The study also analyzed HPV Risk factors for infection, such as sexual behavior, a high number of sexual partners, migrant workers, and frequency of bathing, suggest that sexual transmission remains… HPV An important route of infection; other modes of transmission, such as towels, toilets, and sun exposure, etc., and… HPV The nature of the infection remains unclear. Therefore, HPV Prevention of infection hinges on promoting condom use and reducing the number of sexual partners, rather than adopting excessive precautions regarding everyday household items.

5 . 2 Blood can be tested. HPV Are you infected? ?

Typically, blood tests used to detect viruses most commonly measure specific viral components or assess antibodies produced in response to viral infection. At present, it is believed that… HPV It does not enter the bloodstream and does not cause viremia; therefore, viral detection via blood tests will be negative. ; Because HPV There is/are 100 Multiple subtypes; studies have reported that very low‑titer levels of numerous subtypes can be detected in the blood. HPV Antibodies—however, the clinical significance of detecting these antibodies remains unclear; their presence does not necessarily indicate disease, nor does it imply the need for treatment. At present, no assays are available for routine clinical use. HPV Antibody test kits, thus blood tests are used for diagnosis. HPV There is no scientific evidence for infection.

5 . 3 Common warts, flat warts, plantar warts, and others require examination.

HPV ? ? These warts are of the cutaneous type. HPV Infection, usually of low-risk types. HPV , and the mucosal type that can cause cervical cancer upon infection of the cervix HPV Subtypes differ. Currently approved… HPV All test kits are designed to detect mucosa‑related substances. HPV Currently, there is no dedicated test kit for detecting skin warts; the prevailing view is that low-risk types… HPV No viral testing is required. Mucosal type and cutaneous type. HPV Genetic homology varies; use detection of the mucosal type. HPV Reagent-based testing for skin warts may yield false-negative results. Therefore, common warts, flat warts, plantar warts, and other such lesions do not require testing. HPV , using current methods to detect the mucosal type HPV The method used for detection is also inaccurate.

5 . 4 Testing HPV How to Collect a Specimen Correctly ?

Currently, it is believed that HPV It only infects mucosal epithelial cells and cutaneous keratinocytes, HPV Pathogenicity requires infection of basal layer cells to sustain the infection and lead to disease; therefore, the correct approach is to scrape off the desquamated epidermis from suspected infected skin lesions for examination. Simply collecting secretions or surface scales is inadequate.

5 . 5 HPV Does a positive test result require treatment? ?

Most of it HPV Several months after infection to 2 Within the year, it can be spontaneously cleared by the human immune system and is also referred to as a “transient infection.” HPV Persistent infection is a major factor contributing to carcinogenesis; it is generally believed that an interval of… 1 years or more, continuously 2 The second test detected the same high-risk type. HPV It can be considered that HPV Persistent infection. When the cervix… HPV When the test is positive but cytological examination is negative, it does not necessarily indicate the presence of a lesion; it is often likely to be… HPV The carrying status. Currently, HPV Testing is primarily aimed at screening for high-risk types. HPV , if it is low-risk type HPV Positive, with no rash; no treatment is required. If it is a high-risk type of the same subtype… HPV If the test is positive, it should be combined with cytological examination and followed up regularly; once histological abnormalities are detected, appropriate therapeutic measures should be implemented. This is because, at present, there is no effective anti‑ HPV Medications are not recommended abroad for… HPV Treatment for viral carriage.

5. 6. Does getting vaccinated mean I no longer have to worry about cervical cancer? ?

Incidence of cervical cancer 66% With and HPV16 and 18 Related to the type, the existing… HPV Vaccines are primarily intended to prevent high-risk types. HPV16 and 18 The type does not prevent all high-risk types. HPV , so even after vaccination HPV Even with vaccination, regular cervical cancer screening remains necessary.

5 . 7 HPV How to administer the vaccine ?

Current HPV Vaccines are preventive; they are ineffective against those who have already been infected. HPV It has no therapeutic effect; ideally, the target population should be uninfected before sexual maturity. HPV The group of people. 2015 U.S. guidelines recommend vaccination for women. HPV The age for the vaccine is 11 ~ 12 Age, as early as 9 Annual vaccination ; 13 ~ 26 Although unmarried women and married women who are past the optimal age for vaccination may have missed the best window, they can still benefit from it and should therefore receive the vaccine. 4 Price and 9 The vaccine can be administered to males; the recommended age is 11 ~ 12 year, 13 ~ 21 men of a certain age, especially gay men, HIV Men who test positive should also be vaccinated. HPV Vaccination is administered in doses over a period of six months. 3 the next injection, and 3 The same vaccine brand should be used for each dose.

Frequently Asked Questions

HPV infection is highly prevalent in the general population, and it can also be detected at a certain rate in the skin of healthy individuals; however, HPV Infections are typically transient and can resolve spontaneously. At present, the generally accepted… HPV16 and 18 It is a high-risk subtype that contributes to the development of cervical cancer. HPV6 and 11 Type is a common cause of genital warts, and the approved vaccines are primarily intended to prevent these two conditions. And… HPV Other related malignancies, such as head and neck cancers—particularly high-risk subtypes of oropharyngeal cancer—are still under investigation. In recent years, their incidence has been steadily increasing, warranting close attention. HPV The classification is complex, and the existing… HPV Testing is primarily used to detect a limited number of high-risk types. HPV Subtype, low-risk type HPV Skin warts caused by this do not require testing. HPV 。 HPV The preventive vaccine has been approved for marketing in China. 2016 Year 3 In the month, American scientists announced that they had completed... HPV Phase I clinical trial of a therapeutic vaccine, as research on… HPV With the continuous deepening of our understanding of pathogenic mechanisms, HPV The resulting diseases are expected to be effectively controlled and treated.

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