High-risk human papillomavirus (HPV)-related cancers consist of cervical cancer, anal cancer, penile cancer, vulvar cancer, vaginal cancer, and head and neck cancer (HNC). Of these, the disease burden of HNC is second only to cervical cancer. HNC mostly originates from malignant lesions of squamous epithelial cells and mainly includes oral cavity cancer, pharyngeal cancer (including nasopharyngeal cancer, oropharyngeal cancer, and hypopharyngeal cancer), and laryngeal cancer. Tobacco use, alcohol abuse, and HPV infection are three primary risk factors. Recently, there is an upward trend of HNC incidence globally, especially in high-income countries. In China, the disease burden and trends of HPV-related HNC are still not clear. A few small sample size and single-center studies suggest a high HPV prevalence and increasing trend in HNC. Methodological differences in HPV testing and regional variabilities still exist among these studies. Among the anatomic sites, oropharyngeal cancer has been shown to be caused by HPV infection, but the association of HPV with other sites is still under debate. In addition, there is a paucity of relevant studies. Here, this review narrates the association between HPV infection and HNC, compares the differences between global and Chinese studies, and then explores the importance of HPV infection in various anatomical sites. The main objective is to highlight the research on HPV-related HNC and promote relevant prevention and treatment programs.
Female ; Humans ; Human Papillomavirus Viruses ; Papillomavirus Infections/prevention & control* ; Uterine Cervical Neoplasms/complications* ; Nasopharyngeal Neoplasms/complications* ; Head and Neck Neoplasms/epidemiology* ; Oropharyngeal Neoplasms/epidemiology* ; Papillomaviridae

Objective: To explore the therapeutic effects of transoral robotic surgery (TORS) and traditional surgical modes in oropharyngeal squamous cell carcinoma (OPSCC). Methods: The clinicopathological data of patients with oropharyngeal squamous cell carcinoma treated at Sun Yat-sen University Cancer Center from 2010 to 2018 were retrospectively analyzed. 135 cases were treated with traditional surgery (non-TORS group), while 52 cases were treated with TORS (TORS group). The prognosis of the two groups of patients were analyzed by Kaplan-Meier method and Log rank test, the influencing factors were analyzed by Cox regression model. Results: The 2-year overall survival (OS, 94.2%) and 2-year progression-free survival (PFS, 93.8%) of patients in the TORS group were better than those in the non-TORS group (71.4% and 71.4%, respectively, P<0.05). The 2-year OS (93.3%) and 2-year PFS (92.8%) of TORS group patients in T1-2 stage were better than those of non-TORS group (73.1% and 72.8%, respectively, P<0.05). The 2-year OS (95.8%) and 2-year PFS (95.2%) of patients with stage Ⅰ to Ⅱ in the TORS group were not significantly different from those in the non-TORS group (84.1% and 83.9%, respectively, P>0.05). The 2-year OS (92.9%) and 2-year PFS rate (92.7%) of patients with stage Ⅲ to Ⅳ in the TORS group were better than those in the non-TORS group (64.7% and 63.9%, respectively, P<0.05). The 2-year OS (94.4%) of HPV-positive patients in the TORS group was not significantly different from that in the non-TORS group (83.3%, P=0.222). The 2-year OS of HPV-negative patients in the TORS group (94.1%) was significantly different from that in the non-TORS group (43.7%, P<0.001). HPV status was an independent prognostic factor (P=0.008). Conclusions: TORS has a better prognosis in the treatment of oropharyngeal squamous cell carcinoma compared with the traditional treatment methods. The patients with T1-T2 can achieve better survival benefits after TORS treatment. The HPV-positive OPSCC patients has a better prognosis than that of HPV-negative OPSCC patients, and regardless of HPV status, OPSCC patients in the TORS group could obtain a better survival prognosis.
Head and Neck Neoplasms ; Humans ; Oropharyngeal Neoplasms/surgery* ; Papillomavirus Infections/complications* ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Squamous Cell Carcinoma of Head and Neck/surgery*

Human papillomavirus (HPV) is the most common sexually transmitted virus in males and females worldwide; yet its impact upon male fertility remains unclear. The objective of this study was to evaluate the potential impact of HPV infection in semen on male fertility abnormality. A systematic literature search was performed in PubMed, Medline, Embase, Web of Science, and the Cochrane Library database for relevant publications up to May 6, 2017. The odds ratio (OR), and its corresponding 95% confidence interval (CI), was selected to represent the effect size. Statistical analysis was conducted using STATA 12.0. In total, eight articles, providing data on 1955 participants, were included in this meta-analysis. Collectively, the data suggested that HPV infection of semen was a risk factor for male fertility abnormality with an OR of 3.02 (95% CI: 2.11-4.32; I² = 6.9%). Sensitivity analysis revealed that the results of this study were robust. In conclusion, HPV infection of semen represents a risk factor for male fertility abnormality.
Humans ; Infertility, Male/virology* ; Male ; Papillomaviridae ; Papillomavirus Infections/complications* ; Risk Factors

Human papillomavirus (HPV) infection is one of the worldwide sexually transmitted diseases (STD), and the DNA of HPV can exist in the normal epithelium of reproductive organs of both men and women. Because the majority of HPV infections are asymptomatic, healthy HPV-carriers become the main source of the infection. Studies show that HPV infection in men is correlated with STD, infertility, tumor of reproductive organs, and infection in the sexual partners. Therefore, measures should be taken to reduce male HPV infection, including circumcision, fewer sexual partners, and condom use.
Adult ; Asymptomatic Infections ; Carrier State ; virology ; Circumcision, Male ; Female ; Humans ; Infertility, Male ; virology ; Male ; Papillomaviridae ; Papillomavirus Infections ; complications ; prevention & control ; transmission ; Reproductive Health ; Risk Factors ; Sexual Partners ; Sexually Transmitted Diseases ; virology

OBJECTIVE: We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). METHODS: Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. RESULTS: The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). CONCLUSION: Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.
Cervical Intraepithelial Neoplasia/pathology/surgery/*virology ; Female ; Humans ; Neoplasm Recurrence, Local/*virology ; Neoplasm, Residual ; Papillomaviridae/*isolation & purification ; Papillomavirus Infections/complications/*diagnosis ; Predictive Value of Tests ; Risk Assessment/methods ; Sensitivity and Specificity ; Uterine Cervical Neoplasms/pathology/surgery/*virology

Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.
Dendritic Cells/immunology ; Female ; Genetic Vectors ; Humans ; *Immunotherapy ; Papillomavirus Infections/*complications/therapy ; Papillomavirus Vaccines/therapeutic use ; *Translational Medical Research ; Uterine Cervical Neoplasms/*therapy ; Vaccines, DNA/therapeutic use ; Vaccines, Subunit/therapeutic use

Cervical cancer is the fourth most common cancer in women worldwide, and the human papillomavirus (HPV) is the main causative agent for its development. HPV is a heterogeneous virus, and a persistent infection with a high-risk HPV contributes to the development of cancer. In recent decades, great advances have been made in understanding the molecular biology of HPV, and HPV\'s significance in cervical cancer prevention and management has received increased attention. In this review, we discuss the role of HPV genotyping in cervical cancer by addressing: clinically important issues in HPV virology; the current application of HPV genotyping in clinical medicine; and potential future uses for HPV genotyping.
DNA, Viral/*analysis ; Early Detection of Cancer/*methods ; Female ; *Genome, Viral ; Genotype ; Humans ; Papillomaviridae/classification/*genetics ; Papillomavirus Infections/complications/drug therapy/*virology ; Papillomavirus Vaccines/therapeutic use ; Uterine Cervical Neoplasms/diagnosis/drug therapy/*virology

OBJECTIVE: To evaluate the prognostic implication of human papillomavirus (HPV) viral load in cervical cancer patients who underwent radical hysterectomy. METHODS: We conducted a retrospective review of patients with stage IA2 through stage IIIA cervical carcinoma who underwent radical hysterectomy at Sun Yat-sen University Cancer Center between January 2005 and December 2009. Patients who had undergone preoperative hybrid capture 2 testing to detect HPV DNA were included. A total of 346 patients positive for HPV DNA were enrolled and stratified into two groups according to the median HPV viral load. RESULTS: HPV viral load was significantly correlated with lymphovascular space invasion (p=0.026) and deep stromal invasion (p=0.024). However, other factors, such as age, stage, histologic grade, histologic type, lymph node metastasis, and tumor size, were not significantly associated with viral load. Low HPV viral load was correlated with poor disease-free survival in univariate analysis (p=0.037) and multivariate analysis (p=0.027). There was no significant difference in overall survival with regard to initial HPV viral load. CONCLUSION: Low initial HPV viral load may be a poor prognostic factor for cervical cancer patients who have undergone radical hysterectomy.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/*diagnosis/surgery/virology ; Female ; Humans ; Middle Aged ; Papillomaviridae/*isolation & purification ; Papillomavirus Infections/complications/diagnosis/surgery/virology ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Uterine Cervical Neoplasms/*diagnosis/surgery/virology ; *Viral Load ; Young Adult

The incidence rate of cervical cancer in Korea is still higher than in other developed countries, notwithstanding the national mass-screening program. Furthermore, a new method has been introduced in cervical cancer screening. Therefore, the committee for cervical cancer screening in Korea updated the recommendation statement established in 2002. The new version of the guideline was developed by the committee using evidence-based methods. The committee reviewed the evidence for the benefits and harms of the Papanicolaou test, liquid-based cytology, and human papillomavirus (HPV) testing, and reached conclusions after deliberation. The committee recommends screening for cervical cancer with cytology (Papanicolaou test or liquid-based cytology) every three years in women older than 20 years of age (recommendation A). The cervical cytology combined with HPV test is optionally recommended after taking into consideration individual risk or preference (recommendation C). The current evidence for primary HPV screening is insufficient to assess the benefits and harms of cervical cancer screening (recommendation I). Cervical cancer screening can be terminated at the age of 74 years if more than three consecutive negative cytology reports have been confirmed within 10 years (recommendation D).
Adult ; Age Factors ; Aged ; Early Detection of Cancer/adverse effects/*methods/standards ; Evidence-Based Medicine ; False Positive Reactions ; Female ; Humans ; Hysterectomy ; Middle Aged ; Papillomavirus Infections/diagnosis ; Papillomavirus Vaccines ; Patient Selection ; Pregnancy ; Pregnancy Complications, Neoplastic/diagnosis ; Republic of Korea ; Review Literature as Topic ; Uterine Cervical Neoplasms/*diagnosis ; Vaginal Smears/adverse effects/methods/standards ; Young Adult

OBJECTIVE: To investigate the correlation of laryngeal squamous cell carcinoma (LSCC) and precancerous lesion with HPV infection subtypes and possible clinical relationship. METHOD: Eighty-three cases in paraffin embedded tissues were detected with thirty seven HPV subtypes by flow-through hybridization and gene chip (HybriMax), including 31 cases of laryngeal squamous cell carcinoma, 52 cases of precancerous lesions (29 cases of vocal cord leukoplakia and 23 cases of laryngeal papilloma), and 36 cases of vocal cord polyp as normal vocal mucosa were used as control. RESULT: The total positive rate of HPV was 19.4% in the group of laryngeal squamous cell carcinoma (6/31), 0 in vocal cord leukoplakia, 65.2% in laryngeal papilloma (15/23), and the control group were all negative, HPV virus subtype of HPV-positive laryngeal squamous cell carcinoma were all high-risk HPV16; and there were 6 HPV virus subtypes in laryngeal papilloma (8: HPV6,4: HPV52, 1: HPV11, 1: HPV18, 2: HPV45, 3: HPV16), individual mixing two or more subtypes infection. HPV infection of laryngeal squamous cell carcinoma and precancerous lesions has no statistically significant difference according to gender, high low-risk subtypes. CONCLUSION HPV infection related to laryngeal squamous cell carcinoma and precancerous lesions, but no significant correlation with the subtype distribution of high and low risk; HPV detection is making positive sense to clinical diagnosis of laryngeal carcinoma and precancerous lesions as well as the development of specific HPV subtype vaccine.
Carcinoma, Squamous Cell ; complications ; virology ; Genotype ; Head and Neck Neoplasms ; complications ; virology ; Human papillomavirus 11 ; Humans ; Laryngeal Neoplasms ; complications ; virology ; Papilloma ; complications ; virology ; Papillomaviridae ; classification ; Papillomavirus Infections ; complications ; virology ; Precancerous Conditions ; Squamous Cell Carcinoma of Head and Neck