title: West Side Story (1961 film)

text: A second film adaptation of the musical was released by 20th Century Studios on December 10, 2021, directed by Steven Spielberg and choreographed by Justin Peck, with a screenplay by Tony Kushner. It stars Ansel Elgort as Tony, Rachel Zegler as Maria and Ariana DeBose as Anita; Moreno returns as a new character, Valentina, who is Doc's widow. It received seven nominations at the 94th Academy Awards, including Best Picture, winning one Oscar for DeBose's performance.


title: Ella Purnell

text: Ella Summer Purnell (born 17 September 1996) is an English actress best known for her roles as Jackie in the Showtime drama series "Yellowjackets," Jinx in the Netflix animated television series "Arcane", and Gwyn in the Paramount+/Nickelodeon animated series "". She is also known for her roles in the films "Miss Peregrine's Home for Peculiar Children" (2016), "Churchill" (2017), and "Army of the Dead" (2021).


title: Ella Purnell

text: Ella Summer Purnell was born in the Whitechapel area of East London on 17 September 1996 and raised in Bethnal Green. She attended Bethnal Green Montessori, Forest School, the City of London School for Girls, and the Young Actors Theatre Islington. She also attended weekly classes at the Sylvia Young Theatre School, studying acting, singing, and dance, and was represented by their in-house talent agency.


title: Ella Purnell

text: In 2008, Purnell beat hundreds of other girls for a role in "Oliver!" at London's Theatre Royal, Drury Lane. Towards the end of her time in "Oliver!", she won the role of Young Ruth in Mark Romanek's "Never Let Me Go" – a feature film based on the book by Kazuo Ishiguro. It was released in 2010 to positive reviews. She was then cast as Kayleigh in Gustavo Ron's "Ways to Live Forever", adapted from the book by Sally Nicholls, and as Mia in the Juan Carlos Fresnadillo film "Intruders". Purnell was named by Screen International as one of 10 UK Stars of Tomorrow. She also appeared in the BBC HD Film Short "Candy" in June 2011.


title: Ella Purnell

text: In 2013, Purnell appeared in the feature film "Kick-Ass 2" as the character Dolce. She also appeared as a main character in the independent film, "WildLike", and as a teenage version of the character Maleficent in Disney's 2014 film "Maleficent". In 2016, Purnell starred in Tim Burton's adaptation of "Miss Peregrine's Home for Peculiar Children", based on the novel of the same name, by Ransom Riggs. In 2017, she played Mia in "Access All Areas". Later that year, Purnell appeared in the historical drama film "Churchill", playing Winston Churchill's secretary Helen Garrett.


title: Ella Purnell

text: In 2018, Purnell appeared as Hester Argyll in the BBC mini-series "Ordeal By Innocence", based on the Agatha Christie book of the same name. Later that year, Purnell starred in the leading role of the Starz show "Sweetbitter", based on Stephanie Danler's novel of the same name. She played Tess, a naive 22-year-old who moves to New York City to pursue a new life, and gets caught up in the world of fine dining. It was announced in December 2019 that Starz had cancelled the series. In 2020, Purnell played Lady Maria Grey in Julian Fellowes's period drama "Belgravia", co-produced by ITV and Epix. In 2021, she began starring as Jackie in the Showtime drama series "Yellowjackets". Later that year she voiced Gwyn in the animated series and Jinx in the Netflix animated Arcane (TV series).


title: Human papillomavirus infection

text: Human papillomavirus infection (HPV infection) is caused by a DNA virus from the "Papillomaviridae" family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV and two strains – HPV16 and HPV18 – account for 70% of cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.


title: Human papillomavirus infection

text: An HPV infection is caused by "human papillomavirus", a DNA virus from the papillomavirus family. Over 170 types have been described. An individual can become infected with more than one type of HPV, and the disease is only known to affect humans. More than 40 types may be spread through sexual contact and infect the anus and genitals. Risk factors for persistent infection by sexually transmitted types include early age of first sexual intercourse, multiple sexual partners, smoking, and poor immune function. These types are typically spread by sustained direct skin-to-skin contact, with vaginal and anal sex being the most common methods. HPV infection can also spread from a mother to baby during pregnancy. There is no evidence that HPV can spread via common items like toilet seats, but the types that cause warts may spread via surfaces such as floors. HPV is not killed by common hand sanitizers and disinfectants, increasing the possibility of the virus being transferred via non-living infectious agents called fomites.


title: Human papillomavirus infection

text: HPV vaccines can prevent the most common types of infection. To be most effective, inoculation should occur before the onset of sexual activity, and are therefore recommended between the ages of 9–13 years. Cervical cancer screening, such as the Papanicolaou test ("pap smear"), or examination of the cervix after applying acetic acid, can detect both early cancer and abnormal cells that may develop into cancer. Screening allows for early treatment which results in better outcomes. Screening has reduced both the number of cases and the number of deaths from cervical cancer. Genital warts can be removed by freezing.


title: Human papillomavirus infection

text: Nearly every sexually active individual is infected by HPV at some point in their lives. HPV is the most common sexually transmitted infection (STI), globally. Worldwide in 2018, an estimated 569,000 new cases of cervical cancer occurred, with 311,000 deaths. Around 85% of these cervical cancers occurred in low- and middle-income countries. In the United States, about 30,700 cases of cancer due to HPV occur each year. Roughly 1% of sexually active adults have genital warts. Cases of skin warts have been described since the time of ancient Greece, but that they were caused by a virus was not determined until 1907.


title: Human papillomavirus infection

text: Some HPV types, such as HPV-5, may establish infections that persist for the lifetime of the individual without ever manifesting any clinical symptoms. HPV types 1 and 2 can cause common warts in some infected individuals. HPV types 6 and 11 can cause genital warts and laryngeal papillomatosis.


title: Human papillomavirus infection

text: Many HPV types are carcinogenic. The table below lists common symptoms of HPV infection and the associated strains of HPV.


title: Human papillomavirus infection

text: Skin infections with HPV can cause noncancerous skin growths called warts (verrucae). Warts are caused by a rapid growth of cells on the outer layer of the skin.


title: Human papillomavirus infection

text: While cases of warts have been described since the time of ancient Greece, their viral cause was not known until 1907.


title: Human papillomavirus infection

text: Skin warts are most common in childhood and typically appear and regress spontaneously over the course of weeks to months. Recurring skin warts are common. All HPVs are believed to be capable of establishing long-term "latent" infections in small numbers of stem cells present in the skin. Although these latent infections may never be fully eradicated, immunological control is thought to block the appearance of symptoms such as warts. Immunological control is HPV type-specific, meaning an individual may become resistant to one HPV type while remaining susceptible to other types.


title: Human papillomavirus infection

text: HPV infection of the skin in the genital area is the most common sexually transmitted infection worldwide. Such infections are associated with genital or anal warts (medically known as condylomata acuminata or venereal warts), and these warts are the most easily recognized sign of genital HPV infection.


title: Human papillomavirus infection

text: The strains of HPV that can cause genital warts are usually different from those that cause warts on other parts of the body, such as the hands or feet, or even the inner thighs. A wide variety of HPV types can cause genital warts, but types 6 and 11 together account for about 90% of all cases. However, in total more than 40 types of HPV are transmitted through sexual contact and can infect the skin of the anus and genitals. Such infections may cause genital warts, although they may also remain asymptomatic.


title: Human papillomavirus infection

text: The great majority of genital HPV infections never cause any overt symptoms and are cleared by the immune system in a matter of months. Moreover, people may transmit the virus to others even if they do not display overt symptoms of infection. Most people acquire genital HPV infections at some point in their lives, and about 10% of women are currently infected. A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity. As with cutaneous HPVs, immunity to genital HPV is believed to be specific to a specific strain of HPV.


title: Human papillomavirus infection

text: In addition to genital warts, infection by HPV types 6 and 11 can cause a rare condition known as recurrent laryngeal papillomatosis, in which warts form on the larynx or other areas of the respiratory tract.


title: Human papillomavirus infection

text: These warts can recur frequently, may interfere with breathing, and in extremely rare cases can progress to cancer. For these reasons, repeated surgery to remove the warts may be advisable.


title: Human papillomavirus infection

text: About a dozen HPV types (including types 16, 18, 31, and 45) are called "high-risk" types because persistent infection has been linked to cancer of the oropharynx, larynx, vulva, vagina, cervix, penis, and anus. These cancers all involve sexually transmitted infection of HPV to the stratified epithelial tissue. Individuals infected with both HPV and HIV have an increased risk of developing cervical or anal cancer. HPV type 16 is the strain most likely to cause cancer and is present in about 47% of all cervical cancers, and in many vaginal and vulvar cancers, penile cancers, anal cancers, and cancers of the head and neck.


title: Human papillomavirus infection

text: An estimated 561,200 new cancer cases worldwide (5.2% of all new cancers) were attributable to HPV in 2002, making HPV one of the most important infectious causes of cancer. HPV-associated cancers make up over 5% of total diagnosed cancer cases worldwide, and this incidence is higher in developing countries where it is estimated to cause almost half a million cases each year.


title: Human papillomavirus infection

text: In some infected individuals, their immune systems may fail to control HPV. Lingering infection with high-risk HPV types, such as types 16, 18, 31, and 45, can favor the development of cancer.


title: Human papillomavirus infection

text: HPV is believed to cause cancer by integrating its genome into nuclear DNA. Some of the early genes expressed by HPV, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation. HPV genome integration can also cause carcinogenesis by promoting genomic instability associated with alterations in DNA copy number.


title: Human papillomavirus infection

text: E6 produces a protein (also called E6) that simultaneously binds to two host cell proteins called p53 and E6-Associated Protein (E6-AP). E6AP is an E3 Ubiquitin ligase, an enzyme whose purpose is to tag proteins with a post-translational modification called Ubiquitin. By binding both proteins, E6 induces E6AP to attach a chain of ubiquitin molecules to p53, thereby flagging p53 for proteosomal degradation. Normally, p53 acts to prevent cell growth and promotes cell death in the presence of DNA damage. p53 also upregulates the p21 protein, which blocks the formation of the cyclin D/Cdk4 complex, thereby preventing the phosphorylation of retinoblastoma protein (RB), and in turn, halting cell cycle progression by preventing the activation of E2F. In short, p53 is a tumor-suppressor protein that arrests the cell cycle and prevents cell growth and survival when DNA damage occurs. Thus, the degradation of p53, induced by E6, promotes unregulated cell division, cell growth and cell survival, all characteristics of cancer.


title: Human papillomavirus infection

text: It is important to note, that while the interaction between E6, E6AP and p53 was the first to be characterized, there are multiple other proteins in the host cell which interact with E6 and assist the induction of cancer.


title: Human papillomavirus infection

text: Studies have also shown a link between a wide range of HPV types and squamous cell carcinoma of the skin. In such cases, "in vitro" studies suggest that the E6 protein of the HPV virus may inhibit apoptosis induced by ultraviolet light.


title: Human papillomavirus infection

text: Nearly all cases of cervical cancer are associated with HPV infection, with two types, HPV16 and HPV18, present in 70% of cases. In 2012, twelve HPV types were considered carcinogenic for cervical cancer by the International Agency for Research on Cancer: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. HPV is necessary for cervical cancer to occur. Persistent HPV infection increases the risk for developing cervical carcinoma. Individuals who have an increased incidence of these types of infection are women with HIV/AIDS, who are at a 22-fold increased risk of cervical cancer.


title: Human papillomavirus infection

text: The carcinogenic HPV types in cervical cancer belong to the alphapapillomavirus genus and can be grouped further into HPV clades. The two major carcinogenic HPV clades, alphapapillomavirus-9 (A9) and alphapapillomavirus-7 (A7), contain HPV16 and HPV18, respectively. These two HPV clades were shown to have different effects on tumour molecular characteristics and patient prognosis, with clade A7 being associated with more aggressive pathways and an inferior prognosis.


title: Human papillomavirus infection

text: In 2012, about 528,000 new cases and 266,000 deaths from cervical cancer occurred worldwide. Around 85% of these occurred in the developing world.


title: Human papillomavirus infection

text: Most HPV infections of the cervix are cleared rapidly by the immune system and do not progress to cervical cancer (see below the Clearance subsection in Virology). Because the process of transforming normal cervical cells into cancerous ones is slow, cancer occurs in people having been infected with HPV for a long time, usually over a decade or more (persistent infection). Furthermore, both the HPV infection and cervical cancer drive metabolic modifications that may be correlated with the aberrant regulation of enzymes related to metabolic pathways.


title: Human papillomavirus infection

text: Non-European (NE) HPV16 variants are significantly more carcinogenic than European (E) HPV16 variants.


title: Human papillomavirus infection

text: Studies show a link between HPV infection and anal cancers. Sexually transmitted HPVs are found in a large percentage of anal cancers. Moreover, the risk for anal cancer is 17 to 31 times higher among HIV-positive individuals who were coinfected with high-risk HPV, and 80 times higher for particularly HIV-positive men who have sex with men.


title: Human papillomavirus infection

text: Anal Pap smear screening for anal cancer might benefit some subpopulations of men or women engaging in anal sex. No consensus exists, though, that such screening is beneficial, or who should get an anal Pap smear.


title: Human papillomavirus infection

text: HPV is associated with approximately 50% of penile cancers. In the United States, penile cancer accounts for about 0.5% of all cancer cases in men. HPV16 is the most commonly associated type detected. The risk of penile cancer increases 2- to 3-fold for individuals who are infected with HIV as well as HPV.


title: Human papillomavirus infection

text: Oral infection with high-risk carcinogenic HPV types (most commonly HPV 16) is associated with an increasing number of head and neck cancers. This association is independent of tobacco and alcohol use.


title: Human papillomavirus infection

text: Sexually transmitted forms of HPV account for about 25% of cancers of the mouth and upper throat (the oropharynx) worldwide, but the local percentage varies widely, from 70% in the United States to 4% in Brazil. Engaging in anal or oral sex with an HPV-infected partner may increase the risk of developing these types of cancers.


title: Human papillomavirus infection

text: In the United States, the number of newly diagnosed, HPV-associated head and neck cancers has surpassed that of cervical cancer cases. The rate of such cancers has increased from an estimated 0.8 cases per 100,000 people in 1988 to 4.5 per 100,000 in 2012, and, as of 2015, the rate has continued to increase. Researchers explain these recent data by an increase in oral sex. This type of cancer is more common in men than in women.


title: Human papillomavirus infection

text: The mutational profile of HPV-positive and HPV-negative head and neck cancer has been reported, further demonstrating that they are fundamentally distinct diseases.


title: Human papillomavirus infection

text: Some evidence links HPV to benign and malignant tumors of the upper respiratory tract. The International Agency for Research on Cancer has found that people with lung cancer were significantly more likely to have several high-risk forms of HPV antibodies compared to those who did not have lung cancer. Researchers looking for HPV among 1,633 lung cancer patients and 2,729 people without the lung disease found that people with lung cancer had more types of HPV than noncancer patients did, and among lung cancer patients, the chances of having eight types of serious HPV were significantly increased. In addition, expression of HPV structural proteins by immunohistochemistry and "in vitro" studies suggest HPV presence in bronchial cancer and its precursor lesions. Another study detected HPV in the exhaled breath condensate (EBC), bronchial brushing and neoplastic lung tissue of cases, and found a presence of an HPV infection in 16.4% of the subjects affected by nonsmall cell lung cancer, but in none of the controls. The reported average frequencies of HPV in lung cancers were 17% and 15% in Europe and the Americas, respectively, and the mean number of HPV in Asian lung cancer samples was 35.7%, with a considerable heterogeneity between certain countries and regions.


title: Human papillomavirus infection

text: In very rare cases, HPV may cause epidermodysplasia verruciformis (EV) in individuals with a weakened immune system. The virus, unchecked by the immune system, causes the overproduction of keratin by skin cells, resulting in lesions resembling warts or cutaneous horns which can ultimately transform into skin cancer, but the development is not well understood. The specific types of HPV that are associated with EV are HPV5, HPV8, and HPV14.


title: Human papillomavirus infection

text: Sexually transmitted HPV is divided into two categories: low-risk and high-risk. Low-risk HPVs cause warts on or around the genitals. Type 6 and 11 cause 90% of all genital warts and recurrent respiratory papillomatosis that causes benign tumors in the air passages. High-risk HPVs cause cancer and consist of about a dozen identified types. Types 16 and 18 are responsible for causing most of HPV-caused cancers. These high-risk HPVs cause 5% of the cancers in the world. In the United States, high-risk HPVs cause 3% of all cancer cases in women and 2% in men.


title: Human papillomavirus infection

text: Risk factors for persistent genital HPV infections, which increases the risk for developing cancer, include early age of first sexual intercourse, multiple partners, smoking, and immunosuppression. Genital HPV is spread by sustained direct skin-to-skin contact, with vaginal, anal, and oral sex being the most common methods. Occasionally it can spread from a mother to her baby during pregnancy. HPV is difficult to remove via standard hospital disinfection techniques, and may be transmitted in a healthcare setting on re-usable gynecological equipment, such as vaginal ultrasound transducers. The period of communicability is still unknown, but probably at least as long as visible HPV lesions persist. HPV may still be transmitted even after lesions are treated and no longer visible or present.


title: Human papillomavirus infection

text: Although genital HPV types can be transmitted from mother to child during birth, the appearance of genital HPV-related diseases in newborns is rare. However, the lack of appearance does not rule out asymptomatic latent infection, as the virus has proven to be capable of hiding for decades. Perinatal transmission of HPV types 6 and 11 can result in the development of juvenile-onset recurrent respiratory papillomatosis (JORRP). JORRP is very rare, with rates of about 2 cases per 100,000 children in the United States. Although JORRP rates are substantially higher if a woman presents with genital warts at the time of giving birth, the risk of JORRP in such cases is still less than 1%.


title: Human papillomavirus infection

text: Genital HPV infections are transmitted primarily by contact with the genitals, anus, or mouth of an infected sexual partner.


title: Human papillomavirus infection

text: Of the 120 known human papilloma viruses, 51 species and three subtypes infect the genital mucosa. Fifteen are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), three as probable high-risk (26, 53, and 66), and twelve as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89).


title: Human papillomavirus infection

text: Condoms do not completely protect from the virus because the areas around the genitals including the inner thigh area are not covered, thus exposing these areas to the infected person's skin.


title: Human papillomavirus infection

text: Studies have shown HPV transmission between hands and genitals of the same person and sexual partners. Hernandez tested the genitals and dominant hand of each person in 25 heterosexual couples every other month for an average of seven months. She found two couples where the man's genitals infected the woman's hand with high-risk HPV, two where her hand infected his genitals, one where her genitals infected his hand, two each where he infected his own hand, and she infected her own hand. Hands were not the main source of transmission in these 25 couples, but they were significant.


title: Human papillomavirus infection

text: Partridge reports men's fingertips became positive for high risk HPV at more than half the rate (26% per two years) as their genitals (48%). Winer reports 14% of fingertip samples from sexually active women were positive.


title: Human papillomavirus infection

text: Non-sexual hand contact seems to have little or no role in HPV transmission. Winer found all fourteen fingertip samples from virgin women negative at the start of her fingertip study. In a separate report on genital HPV infection, 1% of virgin women (1 of 76) with no sexual contact tested positive for HPV, while 10% of virgin women reporting non-penetrative sexual contact were positive (7 of 72).


title: Human papillomavirus infection

text: Sharing of possibly contaminated objects, for example, razors, may transmit HPV. Although possible, transmission by routes other than sexual intercourse is less common for female genital HPV infection. Fingers-genital contact is a possible way of transmission but unlikely to be a significant source.


title: Human papillomavirus infection

text: Though it has traditionally been assumed that HPV is not transmissible via blood – as it is thought to only infect cutaneous and mucosal tissues – recent studies have called this notion into question. Historically, HPV DNA has been detected in the blood of cervical cancer patients. In 2005, a group reported that, in frozen blood samples of 57 sexually naive pediatric patients who had vertical or transfusion-acquired HIV infection, 8 (14.0%) of these samples also tested positive for HPV-16. This seems to indicate that it may be possible for HPV to be transmitted via blood transfusion. However, as non-sexual transmission of HPV by other means is not uncommon, this could not be definitively proven. In 2009, a group tested Australian Red Cross blood samples from 180 healthy male donors for HPV, and subsequently found DNA of one or more strains of the virus in 15 (8.3%) of the samples. However, it is important to note that detecting the presence of HPV DNA in blood is not the same as detecting the virus itself in blood, and whether or not the virus itself can or does reside in blood in infected individuals is still unknown. As such, it remains to be determined whether HPV can or cannot be transmitted via blood. This is of concern, as blood donations are not currently screened for HPV, and at least some organizations such as the American Red Cross and other Red Cross societies do not presently appear to disallow HPV-positive individuals from donating blood.


title: Human papillomavirus infection

text: Hospital transmission of HPV, especially to surgical staff, has been documented. Surgeons, including urologists and/or anyone in the room, is subject to HPV infection by inhalation of noxious viral particles during electrocautery or laser ablation of a condyloma (wart). There has been a case report of a laser surgeon who developed extensive laryngeal papillomatosis after providing laser ablation to patients with anogenital condylomata.


title: Human papillomavirus infection

text: HPV infection is limited to the basal cells of stratified epithelium, the only tissue in which they replicate. The virus cannot bind to live tissue; instead, it infects epithelial tissues through micro-abrasions or other epithelial trauma that exposes segments of the basement membrane. The infectious process is slow, taking 12–24 hours for initiation of transcription. It is believed that involved antibodies play a major neutralizing role while the virions still reside on the basement membrane and cell surfaces.


title: Human papillomavirus infection

text: HPV lesions are thought to arise from the proliferation of infected basal keratinocytes. Infection typically occurs when basal cells in the host are exposed to the infectious virus through a disturbed epithelial barrier as would occur during sexual intercourse or after minor skin abrasions. HPV infections have not been shown to be cytolytic; rather, viral particles are released as a result of degeneration of desquamating cells. HPV can survive for many months and at low temperatures without a host; therefore, an individual with plantar warts can spread the virus by walking barefoot.


title: Human papillomavirus infection

text: HPV is a small double-stranded circular DNA virus with a genome of approximately 8000 base pairs. The HPV life cycle strictly follows the differentiation program of the host keratinocyte. It is thought that the HPV virion infects epithelial tissues through micro-abrasions, whereby the virion associates with putative receptors such as alpha integrins, laminins, and annexin A2 leading to entry of the virions into basal epithelial cells through clathrin-mediated endocytosis and/or caveolin-mediated endocytosis depending on the type of HPV. At this point, the viral genome is transported to the nucleus by unknown mechanisms and establishes itself at a copy number of 10-200 viral genomes per cell. A sophisticated transcriptional cascade then occurs as the host keratinocyte begins to divide and become increasingly differentiated in the upper layers of the epithelium.


title: Human papillomavirus infection

text: The phylogeny of the various strains of HPV generally reflects the migration patterns of "Homo sapiens" and suggests that HPV may have diversified along with the human population. Studies suggest that HPV evolved along five major branches that reflect the ethnicity of human hosts, and diversified along with the human population.


title: Human papillomavirus infection

text: Researchers initially identified two major variants of HPV16, European (HPV16-E), and Non-European (HPV16-NE). More recent analyses based on thousands of HPV16 genomes show that indeed two major clades exist, that are further subdivided into four lineages (designated A-D) and even further subdivided into 16 sublineages (A1–4, B1–4, C1–4 and D1–4). The A1-A3 sublineages constitute the European variant, A4 the Asian variant, B1-B4 the African type I variant, C1–C4 the African type II variant, D1 the North American variant, D2 the Asian American type I variant, D3 the Asian American type II variant. The various lineages and sublineages have different oncogenic capacity, where overall, the non-European lineages are considered to increase the risk for cancer. Although HPV16 is a DNA virus, there are signs of recombination among the different lineages. Based on an analysis of more than 3600 genomes, between 0.3 and 1.2% of them could be recombinant. Thus, ideally, genotyping (for cancer-risk assessment) of HPV16 should not be based only on certain genes, but on all genes from the entire genome.


title: Human papillomavirus infection

text: A bioinformatics tool named HPV16-Genotyper performs i) HPV16 lineage genotyping, ii) it detects potential recombination events, iii) it identifies, within the submitted sequences, mutations/SNPs that have been reported (in literature) to increase the risk for cancer.


title: Human papillomavirus infection

text: The two primary oncoproteins of high risk HPV types are E6 and E7. The "E" designation indicates that these two proteins are early proteins (expressed early in the HPV life cycle), while the "L" designation indicates that they are late proteins (late expression). The HPV genome is composed of six early (E1, E2, E4, E5, E6, and E7) open reading frames (ORF), two late (L1 and L2) ORFs, and a non-coding long control region (LCR). After the host cell is infected viral early promoter is activated and a polycistronic primary RNA containing all six early ORFs is transcribed. This polycistronic RNA then undergoes active RNA splicing to generate multiple isoforms of mRNAs. One of the spliced isoform RNAs, E6*I, serves as an E7 mRNA to translate E7 protein. However, viral early transcription subjects to viral E2 regulation and high E2 levels repress the transcription. HPV genomes integrate into host genome by disruption of E2 ORF, preventing E2 repression on E6 and E7. Thus, viral genome integration into host DNA genome increases E6 and E7 expression to promote cellular proliferation and the chance of malignancy. The degree to which E6 and E7 are expressed is correlated with the type of cervical lesion that can ultimately develop.


title: Human papillomavirus infection

text: The E6/E7 proteins inactivate two tumor suppressor proteins, p53 (inactivated by E6) and pRb (inactivated by E7). The viral oncogenes E6 and E7 are thought to modify the cell cycle so as to retain the differentiating host keratinocyte in a state that is favourable to the amplification of viral genome replication and consequent late gene expression. E6 in association with host E6-associated protein, which has ubiquitin ligase activity, acts to ubiquitinate p53, leading to its proteosomal degradation. E7 (in oncogenic HPVs) acts as the primary transforming protein. E7 competes for retinoblastoma protein (pRb) binding, freeing the transcription factor E2F to transactivate its targets, thus pushing the cell cycle forward. All HPV can induce transient proliferation, but only strains 16 and 18 can immortalize cell lines "in vitro". It has also been shown that HPV 16 and 18 cannot immortalize primary rat cells alone; there needs to be activation of the ras oncogene. In the upper layers of the host epithelium, the late genes L1 and L2 are transcribed/translated and serve as structural proteins that encapsidate the amplified viral genomes. Once the genome is encapsidated, the capsid appears to undergo a redox-dependent assembly/maturation event, which is tied to a natural redox gradient that spans both suprabasal and cornified epithelial tissue layers. This assembly/maturation event stabilizes virions, and increases their specific infectivity. Virions can then be sloughed off in the dead squames of the host epithelium and the viral lifecycle continues. A 2010 study has found that E6 and E7 are involved in beta-catenin nuclear accumulation and activation of Wnt signaling in HPV-induced cancers.


title: Human papillomavirus infection

text: Once an HPV virion invades a cell, an active infection occurs, and the virus can be transmitted. Several months to years may elapse before squamous intraepithelial lesions (SIL) develop and can be clinically detected. The time from active infection to clinically detectable disease may make it difficult for epidemiologists to establish which partner was the source of infection.


title: Human papillomavirus infection

text: Most HPV infections are cleared up by most people without medical action or consequences. The table provides data for high-risk types (i.e. the types found in cancers).


title: Human papillomavirus infection

text: Clearing an infection does not always create immunity if there is a new or continuing source of infection. Hernandez' 2005-6 study of 25 couples reports "A number of instances indicated apparent reinfection [from partner] after viral clearance."


title: Human papillomavirus infection

text: Over 170 types of HPV have been identified, and they are designated by numbers. They may be divided into "low-risk" and "high-risk" types. Low-risk types cause warts and high-risk types can cause lesions or cancer.


title: Human papillomavirus infection

text: Guidelines from the American Cancer Society recommend different screening strategies for cervical cancer based on a woman's age, screening history, risk factors and choice of tests. Because of the link between HPV and cervical cancer, the ACS currently recommends early detection of cervical cancer in average-risk asymptomatic adults primarily with cervical cytology by Pap smear, regardless of HPV vaccination status. Women aged 30–65 should preferably be tested every 5 years with both the HPV test and the Pap test. In other age groups, a Pap test alone can suffice unless they have been diagnosed with atypical squamous cells of undetermined significance (ASC-US). Co-testing with a Pap test and HPV test is recommended because it decreases the rate of false-negatives. According to the National Cancer Institute, "The most common test detects DNA from several high-risk HPV types, but it cannot identify the types that are present. Another test is specific for DNA from HPV types 16 and 18, the two types that cause most HPV-associated cancers. A third test can detect DNA from several high-risk HPV types and can indicate whether HPV-16 or HPV-18 is present. A fourth test detects RNA from the most common high-risk HPV types. These tests can detect HPV infections before cell abnormalities are evident.


title: Human papillomavirus infection

text: "Theoretically, the HPV DNA and RNA tests could be used to identify HPV infections in cells taken from any part of the body. However, the tests are approved by the FDA for only two indications: for follow-up testing of women who seem to have abnormal Pap test results and for cervical cancer screening in combination with a Pap test among women over age 30."


title: Human papillomavirus infection

text: Guidelines for oropharyngeal cancer screening by the Preventive Services Task Force and American Dental Association in the U.S. suggest conventional visual examination, but because some parts of the oropharynx are hard to see, this cancer is often only detected in later stages.


title: Human papillomavirus infection

text: The diagnosis of oropharyngeal cancer occurs by biopsy of exfoliated cells or tissues. The National Comprehensive Cancer Network and College of American Pathologists recommend testing for HPV in oropharyngeal cancer. However, while testing is recommended, there is no specific type of test used to detect HPV from oral tumors that is currently recommended by the FDA in the United States. Because HPV type 16 is the most common type found in oropharyngeal cancer, p16 immunohistochemistry is one test option used to determine if HPV is present, which can help determine course of treatment since tumors that are negative for p16 have better outcomes. Another option that has emerged as a reliable option is HPV DNA in situ hybridization (ISH) which allows for visualization of the HPV.


title: Human papillomavirus infection

text: There is not a wide range of tests available even though HPV is common; most studies of HPV used tools and custom analysis not available to the general public. Clinicians often depend on the vaccine among young people and high clearance rates (see Clearance subsection in Virology) to create a low risk of disease and mortality, and treat the cancers when they appear. Others believe that reducing HPV infection in more men and women, even when it has no symptoms, is important (herd immunity) to prevent more cancers rather than just treating them. Where tests are used, negative test results show safety from transmission, and positive test results show where shielding (condoms, gloves) is needed to prevent transmission until the infection clears.


title: Human papillomavirus infection

text: Studies have tested for and found HPV in men, including high-risk types (i.e. the types found in cancers), on fingers, mouth, saliva, anus, urethra, urine, semen, blood, scrotum and penis.


title: Human papillomavirus infection

text: The Qiagen/Digene kit mentioned in the previous section was used successfully off label to test the penis, scrotum and anus of men in long-term relationships with women who were positive for high-risk HPV. 60% of them were found to carry the virus, primarily on the penis. Other studies used cytobrushes and custom analysis.


title: Human papillomavirus infection

text: In one study researchers sampled subjects' urethra, scrotum and penis. Samples taken from the urethra added less than 1% to the HPV rate. Studies like this led Giuliano to recommend sampling the glans, shaft and crease between them, along with the scrotum, since sampling the urethra or anus added very little to the diagnosis. Dunne recommends the glans, shaft, their crease, and the foreskin.


title: Human papillomavirus infection

text: In one study the subjects were asked not to wash their genitals for 12 hours before sampling, including the urethra as well as the scrotum and the penis. Other studies are silent on washing – a particular gap in studies of the hands.


title: Human papillomavirus infection

text: One small study used wet cytobrushes, rather than wet the skin. It found a higher proportion of men to be HPV-positive when the skin was rubbed with a 600 grit emery paper before being swabbed with the brush, rather than swabbed with no preparation. It's unclear whether the emery paper collected the virions or simply loosened them for the swab to collect.


title: Human papillomavirus infection

text: Studies have found self-collection (with emery paper and Dacron swabs) as effective as collection done by a clinician, and sometimes more so, since patients were more willing than a clinician to scrape vigorously. Women had similar success in self-sampling using tampons, swabs, cytobrushes and lavage.


title: Human papillomavirus infection

text: Several studies used cytobrushes to sample fingertips and under fingernails, without wetting the area or the brush.


title: Human papillomavirus infection

text: Other studies analyzed urine, semen, and blood and found varying amounts of HPV, but there is not a publicly available test for those yet.


title: Human papillomavirus infection

text: Although it is possible to test for HPV DNA in other kinds of infections, there are no FDA-approved tests for general screening in the United States or tests approved by the Canadian government, since the testing is inconclusive and considered medically unnecessary.


title: Human papillomavirus infection

text: Genital warts are the only visible sign of low-risk genital HPV and can be identified with a visual check. These visible growths, however, are the result of non-carcinogenic HPV types. Five percent acetic acid (vinegar) is used to identify both warts and squamous intraepithelial neoplasia (SIL) lesions with limited success by causing abnormal tissue to appear white, but most doctors have found this technique helpful only in moist areas, such as the female genital tract. At this time, HPV tests for males are used only in research.


title: Human papillomavirus infection

text: Research into testing for HPV by antibody presence has been done. The approach is looking for an immune response in blood, which would contain antibodies for HPV if the patient is HPV positive. The reliability of such tests has not been proven, as there has not been a FDA approved product as of August 2018; testing by blood would be a less invasive test for screening purposes.


title: Human papillomavirus infection

text: The HPV vaccines can prevent the most common types of infection. To be effective they must be used before an infection occurs and are therefore recommended between the ages of nine and thirteen. Cervical cancer screening, such as with the Papanicolaou test (pap) or looking at the cervix after using acetic acid, can detect early cancer or abnormal cells that may develop into cancer. This allows for early treatment which results in better outcomes. Screening has reduced both the number and deaths from cervical cancer in the developed world. Warts can be removed by freezing.


title: Human papillomavirus infection

text: Three vaccines are available to prevent infection by some HPV types: Gardasil, Gardasil 9 and Cervarix; all three protect against initial infection with HPV types 16 and 18, which cause most of the HPV-associated cancer cases. Gardasil also protects against HPV types 6 and 11, which cause 90% of genital warts. Gardasil is a recombinant quadrivalent vaccine, whereas Cervarix is bivalent, and is prepared from virus-like particles (VLP) of the L1 capsid protein. Gardasil 9 is nonavalent, it has the potential to prevent about 90% of cervical, vulvar, vaginal, and anal cancers. It can protect for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; the latter five cause up to 20% of cervical cancers which were not previously covered.


title: Human papillomavirus infection

text: The vaccines provide little benefit to women already infected with HPV types 16 and 18. For this reason, the vaccine is recommended primarily for those women not yet having been exposed to HPV during sex. The World Health Organization position paper on HPV vaccination clearly outlines appropriate, cost-effective strategies for using HPV vaccine in public sector programs.


title: Human papillomavirus infection

text: There is high-certainty evidence that HPV vaccines protect against precancerous cervical lesions in young women, particularly those vaccinated aged 15 to 26. HPV vaccines do not increase the risk of serious adverse events. Longer follow-up is needed to monitor the impact of HPV vaccines on cervical cancer.


title: Human papillomavirus infection

text: The CDC recommends the vaccines be delivered in two shots at an interval of least 6 months for those aged 11–12, and three doses for those 13 and older. In most countries, they are funded only for female use, but are approved for male use in many countries, and funded for teenage boys in Australia. The vaccine does not have any therapeutic effect on existing HPV infections or cervical lesions. In 2010, 49% of teenage girls in the US got the HPV vaccine.


title: Human papillomavirus infection

text: Following studies suggesting that the vaccine is more effective in younger girls than in older teenagers, the United Kingdom, Switzerland, Mexico, the Netherlands and Quebec began offering the vaccine in a two-dose schedule for girls aged under 15 in 2014.


title: Human papillomavirus infection

text: Cervical cancer screening recommendations have not changed for females who receive HPV vaccine. It remains a recommendation that women continue cervical screening, such as Pap smear testing, even after receiving the vaccine, since it does not prevent all types of cervical cancer.


title: Human papillomavirus infection

text: Both men and women are carriers of HPV. The Gardasil vaccine also protects men against anal cancers and warts and genital warts.


title: Human papillomavirus infection

text: Duration of both vaccines' efficacy has been observed since they were first developed, and is expected to be longlasting.


title: Human papillomavirus infection

text: In December 2014, the FDA approved a nine-valent Gardasil-based vaccine, Gardasil 9, to protect against infection with the four strains of HPV covered by the first generation of Gardasil as well as five other strains responsible for 20% of cervical cancers (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58).


title: Human papillomavirus infection

text: The Centers for Disease Control and Prevention says that male "condom use may reduce the risk for genital human papillomavirus (HPV) infection" but provides a lesser degree of protection compared with other sexual transmitted diseases "because HPV also may be transmitted by exposure to areas (e.g., infected skin or mucosal surfaces) that are not covered or protected by the condom." The strict correlation between chlamydia infection and HPV infection observed in cervical cancer screening, however, suggests that using condoms provides adequate protection for women in this respect.


title: Human papillomavirus infection

text: The virus is unusually hardy, and is immune to most common disinfectants. It is the first virus ever shown to be resistant to inactivation by glutaraldehyde, which is among the most common strong disinfectants used in hospitals. Diluted sodium hypochlorite bleach is effective, but cannot be used on some types of re-usable equipment, such as ultrasound transducers. As a result of these difficulties, there is developing concern about the possibility of transmitting the virus on healthcare equipment, particularly reusable gynecological equipment that cannot be autoclaved. For such equipment, some health authorities encourage use of UV disinfection or a non-hypochlorite "oxidizing‐based high‐level disinfectant [bleach] with label claims for non‐enveloped viruses", such as a strong hydrogen peroxide solution or chlorine dioxide wipes. Such disinfection methods are expected to be relatively effective against HPV.


title: Human papillomavirus infection

text: There is currently no specific treatment for HPV infection. However, the viral infection is usually cleared to undetectable levels by the immune system. According to the Centers for Disease Control and Prevention, the body's immune system clears HPV naturally within two years for 90% of cases (see Clearance subsection in Virology for more detail). However, experts do not agree on whether the virus is eliminated or reduced to undetectable levels, and it is difficult to know when it is contagious.


title: Human papillomavirus infection

text: Follow up care is usually recommended and practiced by many health clinics. Follow-up is sometimes not successful because a portion of those treated do not return to be evaluated. In addition to the normal methods of phone calls and mail, text messaging and email can improve the number of people who return for care. As of 2015 it is unclear the best method of follow up following treatment of cervical intraepithelial neoplasia.


title: Human papillomavirus infection

text: Globally, 12% of women are positive for HPV DNA, with rates varying by age and country. The highest rates of HPV are in younger women, with a rate of 24% in women under 25 years. Rates decline in older age groups in Europe and the Americas, but less so in Africa and Asia. The rates are highest in Sub-Saharan Africa (24%) and Eastern Europe (21%) and lowest in North America (5%) and Western Asia (2%).


title: Human papillomavirus infection

text: The most common types of HPV worldwide are HPV16 (3.2%), HPV18 (1.4%), HPV52 (0.9%), HPV31 (0.8%), and HPV58 (0.7%). High-risk types of HPV are also distributed unevenly, with HPV16 having a rate around 13% in Africa and 30% in West and Central Asia.


title: Human papillomavirus infection

text: Like many diseases, HPV disproportionately affects low-income and resource-poor countries. The higher rates of HPV in Sub-Saharan Africa, for example, may be related to high exposure to human immunodeficiency virus (HIV) in the region. Other factors that impact the global spread of disease are sexual behaviors including age of sexual debut, number of sexual partners, and ease of access to barrier contraception, all of which vary globally.


title: Human papillomavirus infection

text: HPV is estimated to be the most common sexually transmitted infection in the United States. Most sexually active men and women will probably acquire genital HPV infection at some point in their lives. The American Social Health Association estimates that about 75–80% of sexually active Americans will be infected with HPV at some point in their lifetime. By the age of 50 more than 80% of American women will have contracted at least one strain of genital HPV. It was estimated that, in the year 2000, there were approximately 6.2 million new HPV infections among Americans aged 15–44; of these, an estimated 74% occurred to people between ages of 15 and 24. Of the STDs studied, genital HPV was the most commonly acquired. In the United States, it is estimated that 10% of the population has an active HPV infection, 4% has an infection that has caused cytological abnormalities, and an additional 1% has an infection causing genital warts.


title: Human papillomavirus infection

text: Estimates of HPV prevalence vary from 14% to more than 90%. One reason for the difference is that some studies report women who currently have a detectable infection, while other studies report women who have ever had a detectable infection. Another cause of discrepancy is the difference in strains that were tested for.


title: Human papillomavirus infection

text: One study found that, during 2003–2004, at any given time, 26.8% of women aged 14 to 59 were infected with at least one type of HPV. This was higher than previous estimates; 15.2% were infected with one or more of the high-risk types that can cause cancer.


title: Human papillomavirus infection

text: Human papillomavirus is not included among the diseases that are typically reportable to the CDC as of 2011.


title: Human papillomavirus infection

text: On average 538 cases of HPV-associated cancers were diagnosed per year in Ireland during the period 2010 to 2014. Cervical cancer was the most frequent HPV-associated cancer with on average 292 cases per year (74% of the female total, and 54% of the overall total of HPV-associated cancers). A study of 996 cervical cytology samples in an Irish urban female, opportunistically screened population, found an overall HPV prevalence of 19.8%, HPV 16 at 20% and HPV 18 at 12% were the commonest high-risk types detected. In Europe, types 16 and 18 are responsible for over 70% of cervical cancers. Overall rates of HPV-associated invasive cancers may be increasing. Between 1994 and 2014, there was a 2% increase in the rate of HPV-associated invasive cancers per year for both sexes in Ireland.


title: Human papillomavirus infection

text: As HPV is known to be associated with ano-genital warts, these are notifiable to the Health Protection Surveillance Centre (HPSC). Genital warts are the second most common STI in Ireland. There were 1,281 cases of ano-genital warts notified in 2017, which was a decrease on the 2016 figure of 1,593. The highest age-specific rate for both male and female was in the 25–29 year old age range; 53% of cases were among males.


title: Human papillomavirus infection

text: In the Autonomous Region of Inner Mongolia overall HPV prevalence is 14.5% but shows substantial ethnical disparity, the prevalence in Mongolian women (14.9%) being much higher than that of Han participants (4.3%). Urbanization, the number of sex partners, and PAP history appear as risk factors for HPV infection in Han, but not in Mongolian women. The region is thus an important example that epidemiology of HPV is more related to cultural and ethnical factors and not to geography per se.


title: Human papillomavirus infection

text: In 1972, the association of the human papillomaviruses with skin cancer in epidermodysplasia verruciformis was proposed by Stefania Jabłońska in Poland. In 1978, Jabłońska and Gerard Orth at the Pasteur Institute discovered HPV-5 in skin cancer. In 1976 Harald zur Hausen published the hypothesis that human papilloma virus plays an important role in the cause of cervical cancer. In 1983 and 1984 zur Hausen and his collaborators identified HPV16 and HPV18 in cervical cancer.


title: Human papillomavirus infection

text: The Ludwig-McGill HPV Cohort is one of the world's largest longitudinal studies of the natural history of human papillomavirus (HPV) infection and cervical cancer risk. It was established in 1993 by Ludwig Cancer Research and McGill University in Montreal, Canada.


title: Bebe Neuwirth

text: Beatrice "Bebe" Jane Neuwirth ( ; born December 31, 1958) is an American actress, singer, and dancer. On television, she played Dr. Lilith Sternin, Frasier Crane's wife, on both the TV sitcom "Cheers" (in a starring role) and its spin-off "Frasier" (in a recurring guest role). The role won her two Emmy Awards. In 2005, Neuwirth was cast as Bureau Chief/ADA Tracey Kibre in the short-lived "Law & Order" courtroom drama series, "" on NBC that ran for 12 episodes. In film, she portrayed Nora Shepherd in the original "Jumanji" (1995) and "" (2019).


title: Bebe Neuwirth

text: On stage she played the Tony Award–winning roles of Nickie in the revival of "Sweet Charity" (1986) and Velma Kelly in the revival of "Chicago" (1996). Other Broadway musical roles include Lola in the revival of "Damn Yankees" (1994) and Morticia Addams in "The Addams Family" (2010). From 2014 to 2017, she starred as Nadine Tolliver in the CBS political drama "Madam Secretary".


title: Bebe Neuwirth

text: Neuwirth was born in Newark, New Jersey. Her father, , was a mathematician who taught at Princeton University and also designed an encryption device while working at the Institute for Defense Analyses. Her mother, Sydney Anne Neuwirth, is a painter who also danced as an amateur for the Princeton Regional Ballet Company. She has an older brother Peter, a mathematician and actuary who graduated from Harvard. In her youth, Neuwirth rebelled against authority, being placed in custody for smoking marijuana when she was 13.


title: Bebe Neuwirth

text: Neuwirth started taking ballet lessons at the age of five, a year after viewing a production of "The Nutcracker" with her mother. She desired to be a ballet dancer until her early teens, when she realized how restricted her technique was, as well as the standard of ballet education where she lived. Upon viewing the musical "Pippin" in Manhattan at 15, she changed her future plans from becoming a ballerina to being a Broadway musical dancer. After graduating from Princeton High School in 1976, she attended the Juilliard School for dance and left after only a year, disliking the school for having a "stifling creative environment" and no Broadway-style dance training. Immediately after leaving Juilliard in 1977, she took singing and jazz classes at a New York City-based YWCA, one of them taught by Joan Morton Lucas, who appeared in the film "Singin' in the Rain" (1952) and the original Broadway production of "Kiss Me Kate". She performed with the Princeton Ballet Company in "Peter and the Wolf", "The Nutcracker", and "Coppélia", also appearing in community theater musicals.


title: Bebe Neuwirth

text: Studying acting for two years under Suzanne Shepard, Neuwirth made her Broadway debut in the role of Sheila in "A Chorus Line" in 1980. She later appeared in revivals of "Little Me" (1982); "Sweet Charity" (1986), for which she won a Tony Award for Best Featured Actress in a Musical; and "Damn Yankees" (1994).


title: Bebe Neuwirth

text: 1996 saw Neuwirth play Velma Kelly in the Broadway revival of "Chicago". She described the difficulty level of the role as "like performing microsurgery from 8 to 10:20." That role brought her her greatest stage recognition to date and several awards including a Tony Award, Drama Desk Award and Outer Critics Circle Award for Best Leading Actress in a Musical. Neuwirth would later return to the revival of "Chicago" in 2006, this time as Roxie Hart. In 2014 she returned again, this time playing "Mama" Morton, making her the first person to play three different characters at three separate times during the course of a single Broadway run.


title: Bebe Neuwirth

text: She appeared in the musical revue "Here Lies Jenny" which featured songs by Kurt Weill sung and danced by Neuwirth and a four-person supporting cast, as part of an unspoken ambiguous story in an anonymous seedy bar possibly in Berlin in the 1930s. The show ran from May 7 through October 3, 2004, in the Zipper Theater in New York. "Here Lies Jenny" was also presented by Neuwirth in San Francisco in 2005. In 2009, Neuwirth toured a one-woman cabaret show with pianist Scott Cady. The cabaret included music by Kurt Weill, Stephen Sondheim, Tom Waits, John Lennon, Paul McCartney, John Kander and Fred Ebb amongst others. In 2010, she returned to Broadway to create the role of Morticia Addams in the original production of "The Addams Family" opposite Nathan Lane.


title: Bebe Neuwirth

text: In 2019, Neuwirth returned to the stage with the Philadelphia Theatre Company, appearing at the Suzanne Roberts Theater in Philadelphia.


title: Bebe Neuwirth

text: While in Los Angeles waiting to receive a Tony for her appearance in "Sweet Charity" in 1985, Neuwirth auditioned for the role of Dr. Lilith Sternin in the television series "Cheers". At the time, Neuwirth was not interested in doing television work and her character was initially planned to be in only one episode of the series. However, the writers enjoyed writing her dialogue so much that she was written into more episodes of the show, eventually making her one of the series' recurring actors.


title: Bebe Neuwirth

text: Neuwirth's character married Frasier Crane. From the fourth to the ninth season, Neuwirth portrayed Lilith in a regular recurring role, and she appeared on the show as a main star for both seasons ten and eleven. Like Kelsey Grammer when he started on the show as Frasier, she was not immediately given star billing in the opening credits but in the end credits for seasons eight and nine, appearing in the opening credits with her own portrait in seasons ten and eleven. She auditioned for the role with her arm in a sling, following a fall a week earlier. She won two Emmy Awards for the role, in 1990 and 1991. The character also made an appearance in the series "Wings" and in twelve episodes of the "Cheers" spin-off "Frasier", which earned her a 1995 Emmy Award nomination as Outstanding Guest Actress in a Comedy Series. She left "Cheers" in 1993 to go back to her career in dancing, but would make more television appearances in other shows and commercials.


title: Bebe Neuwirth

text: Neuwirth's dip into the movie industry began in 1989 with small roles in films such as "Say Anything..." (1989), "Pacific Heights" (1990), and "Penny Ante" (1990). In 1990 she started doing supporting roles in movies including "Green Card" (1990), "Bugsy" (1991), and "Malice" (1993), in all of which she received acclaim from critics for her performances. Her first lead role came in 1993, when she played a married woman attracted to one of her neighbors in the psychological thriller comedy film "The Paint Job".


title: Bebe Neuwirth

text: Her other credits include "Jumanji", "Summer of Sam", "Liberty Heights", "An Extremely Goofy Movie", "The Adventures of Pinocchio", "Tadpole", "The Associate", "How to Lose a Guy in 10 Days", "The Big Bounce", "Le Divorce", "The Faculty", and Woody Allen's "Celebrity". In 1996, she starred in a pilot for a TV series called "Dear Diary" for ABC which was not picked up. The producers had it edited slightly and put into a single theater for a single weekend in November 1996, and it became one of only two TV pilots to be nominated for an Oscar and the only one to win.


title: Bebe Neuwirth

text: Other small-screen credits include a guest appearance in the second season of "NewsRadio", a small role on "The Adventures of Pete and Pete" (episode: "The Call"), "Deadline" (2000), "Hack" (2003), "" (2005) as ADA Tracey Kibre, "" (1999) as a modeling agent/suspect, the miniseries "Wild Palms", and the fourth season "" episode "" as Lanel.


title: Bebe Neuwirth

text: She appeared as herself in episodes of "Will & Grace", "Strangers with Candy" and "Celebrity Jeopardy!". In 2009, she co-starred as Ms. Kraft in the remake of "Fame". She had a recurring role as Caroline, the literary editor of Jonathan Ames, on the HBO series "Bored to Death". She also had a recurring role on "Blue Bloods".


title: Bebe Neuwirth

text: She starred as Nadine Tolliver in the 2014 CBS political drama "Madam Secretary". In October 2017, Neuwirth announced her decision to leave the series after four seasons. No reason was given. She later reprised the role of Nora Shepherd in "" in 2019; the film grossed 800 million dollars worldwide and received positive reviews from critics.


title: Bebe Neuwirth

text: In 1984, Neuwirth married Paul Dorman. She met him in 1982 after she performed a revue at O'Neal's restaurant in New York, where he was bartending. The two divorced in 1991. In 2009, she married director, producer and writer Chris Calkins at The Players club in Manhattan, in a ceremony officiated by actor Peter Coyote.


title: Bebe Neuwirth

text: In a 2004 article in the newspaper "J. The Jewish News of Northern California", she was reported as describing herself as Jewisha "plain Jew" with "no training". In a 2011 interview she said that she was an "atheist" who "believe[d] in unseen and unproved things" such as reincarnation.


title: Bebe Neuwirth

text: Neuwirth has supported and worked for several non-profit charity organizations. Following two hip replacement surgeries, and after hearing stories of other dancers facing hip problems, Neuwirth was moved to establish the Dancers’ Resource program at The Actors Fund, which caters to financial and physical needs unique to professional dancers. Neuwirth currently serves as vice chair on the board of trustees for The Actors Fund. She has also helped Seeds of Peace.


title: Bebe Neuwirth

text: As an animal lover, she has contributed to the Chatham, New York-based horse rescue group Equine Advocates and the annual pet adoption event Broadway Barks. Neuwirth is particularly fond of cats. In the 1990s, she owned one, Frankie, that she named after architect and writer Frank Lloyd Wright. As of August 2016, she had a black cat, Bobby, a long-haired calico cat, Tallulah, and a mixed Siamese cat, Billie.


title: Russian Orthodox Church

text: The Russian Orthodox Church (ROC; ), alternatively legally known as the Moscow Patriarchate (), is the largest autocephalous Eastern Orthodox Christian church. It has 194 dioceses inside Russia. The primate of the ROC is the Patriarch of Moscow and all Rus'. The ROC, as well as its primate, officially ranks fifth in the Eastern Orthodox order of precedence, immediately below the four ancient patriarchates of the Greek Orthodox Church: Constantinople, Alexandria, Antioch, and Jerusalem.


title: Russian Orthodox Church

text: The Christianization of Kievan Rus' commenced in 988 with the baptism of the Rus' Grand Prince of Kiev — Vladimir the Great — and his people by the clergy of the Ecumenical Patriarch of Constantinople. The ecclesiastical title of Metropolitan of Kiev and all Rus' remained in the jurisdiction of the Ecumenical Patriarchate until 1686.


title: Russian Orthodox Church

text: The ROC currently claims exclusive jurisdiction over the Eastern Orthodox Christians, irrespective of their ethnic background, who reside in the former member republics of the Soviet Union, excluding Georgia. The ROC also created the autonomous Church of Japan and Chinese Orthodox Church. The ROC eparchies in Belarus and Latvia, since the fall of the Soviet Union in the 1990s, enjoy various degrees of self-government, albeit short of the status of formal ecclesiastical autonomy.


title: Russian Orthodox Church

text: The ROC should also not be confused with the Russian Orthodox Church Outside of Russia (or ROCOR, also known as the Russian Orthodox Church Abroad), headquartered in the United States. The ROCOR was instituted in the 1920s by Russian communities outside the Soviet Union, which had refused to recognise the authority of the Moscow Patriarchate that was "de facto" headed by Metropolitan Sergius Stragorodsky. The two churches reconciled on 17 May 2007; the ROCOR is now a self-governing part of the Russian Orthodox Church.


title: Russian Orthodox Church

text: The Christian community that developed into what is now known as the Russian Orthodox Church is traditionally said to have been founded by the Apostle Andrew, who is thought to have visited Scythia and Greek colonies along the northern coast of the Black Sea. According to one of the legends, Andrew reached the future location of Kyiv and foretold the foundation of a great Christian city. The spot where he reportedly erected a cross is now marked by St. Andrew's Cathedral.


title: Russian Orthodox Church

text: As Kyiv was losing its political, cultural, and economical significance due to the Mongol invasion, Metropolitan Maximus moved to Vladimir in 1299; his successor, Metropolitan Peter moved the residence to Moscow in 1325.


title: Russian Orthodox Church

text: In 1439, at the Council of Florence, some Orthodox hierarchs from Byzantium as well as Metropolitan Isidore, who represented the Russian Church, signed a union with the Roman Church, whereby the Eastern Church would recognise the primacy of the Pope. However, the Moscow Prince Vasili II rejected the act of the Council of Florence brought to Moscow by Isidore in March 1441. Isidore was in the same year removed from his position as an apostate and expelled from Moscow. The Russian metropolitanate remained effectively vacant for the next few years due largely to the dominance of Uniates in Constantinople then. In December 1448, Jonas, a Russian bishop, was installed by the Council of Russian bishops in Moscow as Metropolitan of Kiev and All Russia (with permanent residence in Moscow) without the consent from Constantinople. This occurred five years prior to the fall of Constantinople in 1453 and, unintentionally, signified the beginning of an effectively independent church structure in the Moscow (North-Eastern Russian) part of the Russian Church. Subsequently, there developed a theory in Moscow that saw Moscow as the Third Rome, the legitimate successor to Constantinople, and the Primate of the Moscow Church as head of all the Russian Church. Meanwhile, the newly established in 1458 Russian Orthodox (initially Uniate) metropolitanate in Kiev (then in the Grand Duchy of Lithuania and subsequently in the Polish–Lithuanian Commonwealth) continued under the jurisdiction of the Ecumenical See until 1686, when it was provisionally transferred to the jurisdiction of Moscow.


title: Russian Orthodox Church

text: During the reign of Tsar Fyodor I, his brother-in-law, Boris Godunov, contacted the Ecumenical Patriarch of Constantinople, who "was much embarrassed for want of funds".


title: Russian Orthodox Church

text: Several years after the Council of Pereyaslav (1654) that heralded the subsequent incorporation of eastern regions of the Polish–Lithuanian Commonwealth into the Tsardom of Russia, the see of the Metropolitan of Kiev and all Rus' was transferred to the Moscow Patriarchate (1686).


title: Russian Orthodox Church

text: Peter the Great (1682–1725) had an agenda of radical modernization of Russian government, army, dress and manners. He made Russia a formidable political power. Peter was not religious and had a low regard for the Church, so he put it under tight governmental control. He replaced the Patriarch with a Holy Synod, which he controlled. The Tsar appointed all bishops. A clerical career was not a route chosen by upper-class society. Most parish priests were sons of priests, were very poorly educated, and very poorly paid. The monks in the monasteries had a slightly higher status; they were not allowed to marry. Politically, the church was impotent. Catherine the Great later in the 18th century seized most of the church lands, and put the priests on a small salary supplemented by fees for services such as baptism and marriage.


title: Russian Orthodox Church

text: In the aftermath of the Treaty of Pereyaslav, the Ottomans (supposedly acting on behalf of the Russian regent Sophia Alekseyevna) pressured the Patriarch of Constantinople into transferring the Metropolitan of Kiev and all Rus' from the jurisdiction of Constantinople to that of Moscow. The handover brought millions of faithful and half a dozen dioceses under the ultimate administrative care of the Patriarch of Moscow and all Rus' (and later of the Holy Synod of Russia), leading to the significant Ukrainian presence in the Russian Church, which continued well into the 18th century, with Theophan Prokopovich, Epiphanius Slavinetsky, Stephen Yavorsky and Demetrius of Rostov being among the most notable representatives of this trend. The exact terms and conditions of the handover of the Kiev Metropolis are a contested issue.


title: Russian Orthodox Church

text: In 1700, after Patriarch Adrian's death, Peter the Great prevented a successor from being named, and in 1721, following the advice of Theophan Prokopovich, Archbishop of Pskov, the Holy and Supreme Synod was established under Archbishop Stephen Yavorsky to govern the church instead of a single primate. This was the situation until shortly after the Russian Revolution of 1917, at which time the Local Council (more than half of its members being lay persons) adopted the decision to restore the Patriarchate. On 5 November (according to the Julian calendar) a new patriarch, Tikhon, was named through casting lots.


title: Russian Orthodox Church

text: The late 18th century saw the rise of "starchestvo" under Paisiy Velichkovsky and his disciples at the Optina Monastery. This marked a beginning of a significant spiritual revival in the Russian Church after a lengthy period of modernization, personified by such figures as Demetrius of Rostov and Platon of Moscow. Aleksey Khomyakov, Ivan Kireevsky and other lay theologians with Slavophile leanings elaborated some key concepts of the renovated Orthodox doctrine, including that of "sobornost". The resurgence of Eastern Orthodoxy was reflected in Russian literature, an example is the figure of Starets Zosima in Fyodor Dostoyevsky's "Brothers Karamazov".


title: Russian Orthodox Church

text: In the Russian Orthodox Church, the clergy, over time, formed a hereditary caste of priests. Marrying outside of these priestly families was strictly forbidden; indeed, some bishops did not even tolerate their clergy marrying outside of the priestly families of their diocese.


title: Russian Orthodox Church

text: In 1909, a volume of essays appeared under the title "Vekhi" ("Milestones" or "Landmarks"), authored by a group of leading left-wing intellectuals, including Sergei Bulgakov, Peter Struve and former Marxists.


title: Russian Orthodox Church

text: It is possible to see a similarly renewed vigor and variety in religious life and spirituality among the lower classes, especially after the upheavals of 1905. Among the peasantry, there was widespread interest in spiritual-ethical literature and non-conformist moral-spiritual movements, an upsurge in pilgrimage and other devotions to sacred spaces and objects (especially icons), persistent beliefs in the presence and power of the supernatural (apparitions, possession, walking-dead, demons, spirits, miracles and magic), the renewed vitality of local "ecclesial communities" actively shaping their own ritual and spiritual lives, sometimes in the absence of clergy, and defining their own sacred places and forms of piety. Also apparent was the proliferation of what the Orthodox establishment branded as "sectarianism", including both non-Eastern Orthodox Christian denominations, notably Baptists, and various forms of popular Orthodoxy and mysticism.


title: Russian Orthodox Church

text: In 1914, there were 55,173 Russian Orthodox churches and 29,593 chapels, 112,629 priests and deacons, 550 monasteries and 475 convents with a total of 95,259 monks and nuns in Russia.


title: Russian Orthodox Church

text: The year 1917 was a major turning point in Russian history, and also the Russian Orthodox Church. In early March 1917 (O.S.), the Tsar was forced to abdicate, the Russian empire began to implode, and the government's direct control of the Church was all but over by August 1917. On 15 August (O.S.), in the Moscow Dormition Cathedral in the Kremlin, the Local ("Pomestniy") Council of the ROC, the first such convention since the late 17th century, opened. The council continued its sessions until September 1918 and adopted a number of important reforms, including the restoration of Patriarchate, a decision taken 3 days after the Bolsheviks overthrew the Provisional Government in Petrograd on 25 October (O.S.). On 5 November, Metropolitan Tikhon of Moscow was selected as the first Russian Patriarch after about 200 years of Synodal rule.


title: Russian Orthodox Church

text: In early February 1918, the Bolshevik-controlled government of Soviet Russia enacted the Decree on separation of church from state and school from church that proclaimed separation of church and state in Russia, freedom to "profess any religion or profess none", deprived religious organisations of the right to own any property and legal status. Legal religious activity in the territories controlled by Bolsheviks was effectively reduced to services and sermons inside church buildings. The Decree and attempts by Bolshevik officials to requisition church property caused sharp resentment on the part of the ROC clergy and provoked violent clashes on some occasions: on 1 February (19 January O.S.), hours after the bloody confrontation in Petrograd's Alexander Nevsky Lavra between the Bolsheviks trying to take control of the monastery's premises and the believers, Patriarch Tikhon issued a proclamation that anathematised the perpetrators of such acts.


title: Russian Orthodox Church

text: The church was caught in the crossfire of the Russian Civil War that began later in 1918, and church leadership, despite their attempts to be politically neutral (from the autumn of 1918), as well as the clergy generally were perceived by the Soviet authorities as a "counter-revolutionary" force and thus subject to suppression and eventual liquidation.


title: Russian Orthodox Church

text: The Soviet Union, formally created in December 1922, was the first state to have elimination of religion as an ideological objective espoused by the country's ruling political party. Toward that end, the Communist regime confiscated church property, ridiculed religion, harassed believers, and propagated materialism and atheism in schools. Actions toward particular religions, however, were determined by State interests, and most organized religions were never outlawed.


title: Russian Orthodox Church

text: Orthodox clergy and active believers were treated by the Soviet law-enforcement apparatus as anti-revolutionary elements and were habitually subjected to formal prosecutions on political charges, arrests, exiles, imprisonment in camps, and later could also be incarcerated in mental hospitals.


title: Russian Orthodox Church

text: However, the Soviet policy vis-a-vis organised religion vacillated over time between, on the one hand, a utopian determination to substitute secular rationalism for what they considered to be an outmoded "superstitious" worldview and, on the other, pragmatic acceptance of the tenaciousness of religious faith and institutions. In any case, religious beliefs and practices did persist, not only in the domestic and private spheres but also in the scattered public spaces allowed by a state that recognized its failure to eradicate religion and the political dangers of an unrelenting culture war.


title: Russian Orthodox Church

text: The Russian Orthodox church was drastically weakened in May 1922, when the Renovated (Living) Church, a reformist movement backed by the Soviet secret police, broke away from Patriarch Tikhon (also see the Josephites and the Russian True Orthodox Church), a move that caused division among clergy and faithful that persisted until 1946.


title: Russian Orthodox Church

text: Between 1917 and 1935, 130,000 Eastern Orthodox priests were arrested. Of these, 95,000 were put to death. Many thousands of victims of persecution became recognized in a special canon of saints known as the "new martyrs and confessors of Russia".


title: Russian Orthodox Church

text: When Patriarch Tikhon died in 1925, the Soviet authorities forbade patriarchal election. Patriarchal "locum tenens" (acting Patriarch) Metropolitan Sergius (Stragorodsky, 1887–1944), going against the opinion of a major part of the church's parishes, in 1927 issued a declaration accepting the Soviet authority over the church as legitimate, pledging the church's cooperation with the government and condemning political dissent within the church. By this declaration, Sergius granted himself authority that he, being a deputy of imprisoned Metropolitan Peter and acting against his will, had no right to assume according to the XXXIV Apostolic canon, which led to a split with the Russian Orthodox Church Outside Russia abroad and the Russian True Orthodox Church (Russian Catacomb Church) within the Soviet Union, as they allegedly remained faithful to the Canons of the Apostles, declaring the part of the church led by Metropolitan Sergius schism, sometimes coined "Sergianism". Due to this canonical disagreement it is disputed which church has been the legitimate successor to the Russian Orthodox Church that had existed before 1925.


title: Russian Orthodox Church

text: In 1927, Metropolitan Eulogius (Georgiyevsky) of Paris broke with the ROCOR (along with Metropolitan Platon (Rozhdestvensky) of New York, leader of the Russian Metropolia in America). In 1930, after taking part in a prayer service in London in supplication for Christians suffering under the Soviets, Evlogy was removed from office by Sergius and replaced. Most of Evlogy's parishes in Western Europe remained loyal to him; Evlogy then petitioned Ecumenical Patriarch Photius II to be received under his canonical care and was received in 1931, making a number of parishes of Russian Orthodox Christians outside Russia, especially in Western Europe an Exarchate of the Ecumenical Patriarchate as the Archdiocese of Russian Orthodox churches in Western Europe.


title: Russian Orthodox Church

text: Moreover, in the 1929 elections, the Orthodox Church attempted to formulate itself as a full-scale opposition group to the Communist Party, and attempted to run candidates of its own against the Communist candidates. Article 124 of the 1936 Soviet Constitution officially allowed for freedom of religion within the Soviet Union, and along with initial statements of it being a multi-candidate election, the Church again attempted to run its own religious candidates in the 1937 elections. However the support of multicandidate elections was retracted several months before the elections were held and in neither 1929 nor 1937 were any candidates of the Orthodox Church elected.


title: Russian Orthodox Church

text: After Nazi Germany's attack on the Soviet Union in 1941, Joseph Stalin revived the Russian Orthodox Church to intensify patriotic support for the war effort. In the early hours of 5 September 1943, Metropolitans Sergius (Stragorodsky), Alexius (Simansky) and Nicholas (Yarushevich) had a meeting with Stalin and received permission to convene a council on 8 September 1943, which elected Sergius Patriarch of Moscow and all the Rus'. This is considered by some as violation of the XXX Apostolic canon, as no church hierarch could be consecrated by secular authorities. A new patriarch was elected, theological schools were opened, and thousands of churches began to function. The Moscow Theological Academy Seminary, which had been closed since 1918, was re-opened.


title: Russian Orthodox Church

text: In December 2017, the Security Service of Ukraine lifted classified top secret status of documents revealing that the NKVD of the USSR and its units were engaged in the selection of candidates for participation in the 1945 Local Council from the representatives of the clergy and the laity. NKVD demanded "to outline persons who have religious authority among the clergy and believers, and at the same time checked for civic or patriotic work". In the letter sent in September 1944, it was emphasized: "It is important to ensure that the number of nominated candidates is dominated by the agents of the NKBD, capable of holding the line that we need at the Council".


title: Russian Orthodox Church

text: A new and widespread persecution of the church was subsequently instituted under the leadership of Nikita Khrushchev and Leonid Brezhnev. A second round of repression, harassment and church closures took place between 1959 and 1964 when Nikita Khrushchev was in office. The number of Orthodox churches fell from around 22,000 in 1959 to around 8,000 in 1965; priests, monks and faithful were killed or imprisoned and the number of functioning monasteries was reduced to less than twenty.


title: Russian Orthodox Church

text: Subsequent to Khrushchev's overthrow, the Church and the government remained on unfriendly terms until 1988. In practice, the most important aspect of this conflict was that openly religious people could not join the Communist Party of the Soviet Union, which meant that they could not hold any political office. However, among the general population, large numbers remained religious.


title: Russian Orthodox Church

text: Some Orthodox believers and even priests took part in the dissident movement and became prisoners of conscience. The Orthodox priests Gleb Yakunin, Sergiy Zheludkov and others spent years in Soviet prisons and exile for their efforts in defending freedom of worship. Among the prominent figures of that time were Dmitri Dudko and Aleksandr Men. Although he tried to keep away from practical work of the dissident movement intending to better fulfil his calling as a priest, there was a spiritual link between Men and many of the dissidents. For some of them he was a friend; for others, a godfather; for many (including Yakunin), a spiritual father.


title: Russian Orthodox Church

text: By 1987 the number of functioning churches in the Soviet Union had fallen to 6,893 and the number of functioning monasteries to just 18. In 1987 in the Russian SFSR, between 40% and 50% of newborn babies (depending on the region) were baptized. Over 60% of all deceased received Christian funeral services.


title: Russian Orthodox Church

text: Beginning in the late 1980s, under Mikhail Gorbachev, the new political and social freedoms resulted in the return of many church buildings to the church, so they could be restored by local parishioners. A pivotal point in the history of the Russian Orthodox Church came in 1988, the millennial anniversary of the Christianization of Kievan Rus'. Throughout the summer of that year, major government-supported celebrations took place in Moscow and other cities; many older churches and some monasteries were reopened. An implicit ban on religious propaganda on state TV was finally lifted. For the first time in the history of the Soviet Union, people could watch live transmissions of church services on television.


title: Russian Orthodox Church

text: Gleb Yakunin, a critic of the Moscow Patriarchate who was one of those who briefly gained access to the KGB's archives in the early 1990s, argued that the Moscow Patriarchate was "practically a subsidiary, a sister company of the KGB". Critics charge that the archives showed the extent of active participation of the top ROC hierarchs in the KGB efforts overseas. George Trofimoff, the highest-ranking US military officer ever indicted for, and convicted of, espionage by the United States and sentenced to life imprisonment on 27 September 2001, had been "recruited into the service of the KGB" by Igor Susemihl (a.k.a. Zuzemihl), a bishop in the Russian Orthodox Church (subsequently, a high-ranking hierarch—the ROC Metropolitan Iriney of Vienna, who died in July 1999).


title: Russian Orthodox Church

text: Konstanin Kharchev, former chairman of the Soviet Council on Religious Affairs, explained: "Not a single candidate for the office of bishop or any other high-ranking office, much less a member of the Holy Synod, went through without confirmation by the Central Committee of the CPSU and the KGB". Professor Nathaniel Davis points out: "If the bishops wished to defend their people and survive in office, they had to collaborate to some degree with the KGB, with the commissioners of the Council for Religious Affairs, and with other party and governmental authorities". Patriarch Alexy II, acknowledged that compromises were made with the Soviet government by bishops of the Moscow Patriarchate, himself included, and he publicly repented for these compromises.


title: Russian Orthodox Church

text: Metropolitan Alexy (Ridiger) of Leningrad, ascended the patriarchal throne in 1990 and presided over the partial return of Orthodox Christianity to Russian society after 70 years of repression, transforming the ROC to something resembling its pre-communist appearance; some 15,000 churches had been re-opened or built by the end of his tenure, and the process of recovery and rebuilding has continued under his successor Patriarch Kirill. According to official figures, in 2016 the Church had 174 dioceses, 361 bishops, and 34,764 parishes served by 39,800 clergy. There were 926 monasteries and 30 theological schools.


title: Russian Orthodox Church

text: The Russian Church also sought to fill the ideological vacuum left by the collapse of Communism and even, in the opinion of some analysts, became "a separate branch of power".


title: Russian Orthodox Church

text: In August 2000, the ROC adopted its Basis of the Social Concept and in July 2008, its Basic Teaching on Human Dignity, Freedom and Rights.


title: Russian Orthodox Church

text: Under Patriarch Aleksey, there were difficulties in the relationship between the Russian Orthodox Church and the Vatican, especially since 2002, when Pope John Paul II created a Catholic diocesan structure for Russian territory. The leaders of the Russian Church saw this action as a throwback to prior attempts by the Vatican to proselytize the Russian Orthodox faithful to become Roman Catholic. This point of view was based upon the stance of the Russian Orthodox Church (and the Eastern Orthodox Church) that the Church of Rome is in schism, after breaking off from the Orthodox Church. The Roman Catholic Church, on the other hand, while acknowledging the primacy of the Russian Orthodox Church in Russia, believed that the small Roman Catholic minority in Russia, in continuous existence since at least the 18th century, should be served by a fully developed church hierarchy with a presence and status in Russia, just as the Russian Orthodox Church is present in other countries (including constructing a cathedral in Rome, near the Vatican).


title: Russian Orthodox Church

text: There occurred strident conflicts with the Ecumenical Patriarchate, most notably over the Orthodox Church in Estonia in the mid-1990s, which resulted in unilateral suspension of eucharistic relationship between the churches by the ROC. The tension lingered on and could be observed at the meeting in Ravenna in early October 2007 of participants in the Orthodox–Catholic Dialogue: the representative of the Moscow Patriarchate, Bishop Hilarion Alfeyev, walked out of the meeting due to the presence of representatives from the Estonian Apostolic Orthodox Church which is in the jurisdiction of the Ecumenical Patriarchate. At the meeting, prior to the departure of the Russian delegation, there were also substantive disagreements about the wording of a proposed joint statement among the Orthodox representatives. After the departure of the Russian delegation, the remaining Orthodox delegates approved the form which had been advocated by the representatives of the Ecumenical Patriarchate. The Ecumenical See's representative in Ravenna said that Hilarion's position "should be seen as an expression of authoritarianism whose goal is to exhibit the influence of the Moscow Church. But like last year in Belgrade, all Moscow achieved was to isolate itself once more since no other Orthodox Church followed its lead, remaining instead faithful to Constantinople."


title: Russian Orthodox Church

text: Canon Michael Bourdeaux, former president of the Keston Institute, said in January 2008 that "the Moscow Patriarchate acts as though it heads a state church, while the few Orthodox clergy who oppose the church-state symbiosis face severe criticism, even loss of livelihood." Such a view is backed up by other observers of Russian political life. Clifford J. Levy of "The New York Times" wrote in April 2008: "Just as the government has tightened control over political life, so, too, has it intruded in matters of faith. The Kremlin's surrogates in many areas have turned the Russian Orthodox Church into a de facto official religion, warding off other Christian denominations that seem to offer the most significant competition for worshipers. [...] This close alliance between the government and the Russian Orthodox Church has become a defining characteristic of Mr. Putin's tenure, a mutually reinforcing choreography that is usually described here as working 'in symphony'."


title: Russian Orthodox Church

text: Throughout Patriarch Alexy's reign, the massive program of costly restoration and reopening of devastated churches and monasteries (as well as the construction of new ones) was criticized for having eclipsed the church's principal mission of evangelizing.


title: Russian Orthodox Church

text: On 5 December 2008, the day of Patriarch Alexy's death, the "Financial Times" said: "While the church had been a force for liberal reform under the Soviet Union, it soon became a center of strength for conservatives and nationalists in the post-communist era. Alexei's death could well result in an even more conservative church."


title: Russian Orthodox Church

text: On 27 January 2009, the ROC Local Council elected Metropolitan Kirill of Smolensk Patriarch of Moscow and All Rus′ by 508 votes out of a total of 700. He was enthroned on 1 February 2009.


title: Russian Orthodox Church

text: Patriarch Kirill implemented reforms in the administrative structure of the Moscow Patriarchate: on 27 July 2011 the Holy Synod established the Central Asian Metropolitan District, reorganizing the structure of the Church in Tajikistan, Uzbekistan, Kyrgyzstan and Turkmenistan. In addition, on 6 October 2011, at the request of the Patriarch, the Holy Synod introduced the metropoly (Russian: митрополия, mitropoliya), administrative structure bringing together neighboring eparchies.


title: Russian Orthodox Church

text: Under Patriarch Kirill, the ROC continued to maintain close ties with the Kremlin enjoying the patronage of president Vladimir Putin, who has sought to mobilize Russian Orthodoxy both inside and outside Russia. Patriarch Kirill endorsed Putin's election in 2012, referring in February to Putin's tenure in the 2000s as "God's miracle." Nevertheless, Russian inside sources were quoted in the autumn 2017 as saying that Putin's relationship with Patriarch Kirill had been deteriorating since 2014 due to the fact that the presidential administration had been misled by the Moscow Patriarchate as to the extent of support for pro-Russian uprising in eastern Ukraine; also, due to Kirill's personal unpopularity he had come to be viewed as a political liability.


title: Russian Orthodox Church

text: In 2018, the Moscow Patriarchate's traditional rivalry with the Patriarchate of Constantinople, coupled with Moscow's anger over the decision to grant autocephaly to the Ukrainian church by the Ecumenical Patriarch, led the ROC to boycott the Holy Great Council that had been prepared by all the Orthodox Churches for decades.


title: Russian Orthodox Church

text: The Holy Synod of the ROC, at its session on 15 October 2018, severed full communion with the Ecumenical Patriarchate of Constantinople. The decision was taken in response to the move made by the Patriarchate of Constantinople a few days prior that effectively ended the Moscow Patriarchate's jurisdiction over Ukraine and promised autocephaly to Ukraine, the ROC's and the Kremlin's fierce opposition notwithstanding.


title: Russian Orthodox Church

text: While the Ecumenical Patriarchate finalised the establishment of the Orthodox Church of Ukraine on 5 January 2019, the ROC continued to claim that the only legitimate Orthodox jurisdiction in the country, was its branch. Under a law of Ukraine adopted at the end of 2018, the latter was required to change its official title so as to disclose its affiliation with the Russian Orthodox Church based in an "aggressor state". On 11 December 2019 the Supreme Court of Ukraine allowed the Ukrainian Orthodox Church of the Moscow Patriarchate (UOC-MP) to retain its name.


title: Russian Orthodox Church

text: In October 2019, the ROC unilaterally severed communion with the Church of Greece following the latter's recognition of the Ukrainian autocephaly. On 3 November, Patriarch Kirill failed to commemorate the Primate of the Church of Greece, Archbishop Ieronymos II of Athens, during a liturgy in Moscow. Additionally, the ROC leadership imposed pilgrimage bans for its faithful in respect of a number of dioceses in Greece, including that of Athens.


title: Russian Orthodox Church

text: On 8 November 2019, the Russian Orthodox Church announced that Patriarch Kirill would stop commemorating the Patriarch of Alexandria and all Africa after the latter and his Church recognized the OCU that same day.


title: Russian Orthodox Church

text: On 27 September 2021, the ROC established a religious day of remembrance for all Eastern Orthodox Christians which were persecuted by the Soviet regime. This day is the 30 October.


title: Russian Orthodox Church

text: Metropolitan Onufriy of Kyiv, primate of the Ukrainian Orthodox Church (Moscow Patriarchate) (UOC-MP) called the war "a disaster" stating that "The Ukrainian and Russian peoples came out of the Dnieper Baptismal font, and the war between these peoples is a repetition of the sin of Cain, who killed his own brother out of envy. Such a war has no justification either from God or from people." He also appealed directly to Putin, asking for an immediate end to the "fratricidal war". In April 2022, after the Russian invasion, many UOC-MP parishes signaled their intention to switch allegiance to the Orthodox Church of Ukraine. The attitude and stance of Patriarch Kirill of Moscow to the war is one of the oft quoted reasons. The head of the Russian Orthodox Church in Lithuania, Metropolitan Innocent (Vasilyev), called Patriarch Kirill's "political statements about the war" his "personal opinion." On 7 March 2022, condemned the Russian invasion of Ukraine.


title: Russian Orthodox Church

text: On 27 February 2022, a group of Russian Orthodox priests published an open letter calling for an end to the war and criticized the suppression of non-violent anti-war protests in Russia. On 6 March 2022, Russian Orthodox priest of Moscow Patriarchate's Kostroma Diocese was fined by Russian authorities for anti-war sermon and stressing the importance of the commandment “Thou shalt not kill.”


title: Russian Orthodox Church

text: The ROC constituent parts in other than the Russian Federation countries of its exclusive jurisdiction such as Ukraine, Belarus et al., are legally registered as separate legal entities in accordance with the relevant legislation of those independent states.


title: Russian Orthodox Church

text: Ecclesiastiacally, the ROC is organized in a hierarchical structure. The lowest level of organization, which normally would be a single ROC building and its attendees, headed by a priest who acts as Father superior (, "nastoyatel"), constitute a parish (, "prihod"). All parishes in a geographical region belong to an eparchy (—equivalent to a Western diocese). Eparchies are governed by bishops (, episcop or архиерей, archiereus). There are 261 Russian Orthodox eparchies worldwide (June 2012).


title: Russian Orthodox Church

text: Further, some eparchies may be organized into exarchates (currently the Belarusian exarchate), and since 2003 into metropolitan districts (митрополичий округ), such as the ROC eparchies in Kazakhstan and the Central Asia (Среднеазиатский митрополичий округ).