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The unprecedented four-day meeting, starting on Thursday, brings together presidents of national Roman Catholic bishops conferences, Vatican officials, experts and heads of male and female religious orders.
"I am absolutely convinced that our credibility in this area is at stake," said Father Federico Lombardi, who Pope Francis has chosen to moderate the meeting.
"We have to get to the root of this problem and show our ability to undergo a cure as a Church that proposes to be a teacher or it would be better for us to get into another line of work," he told reporters.
The meeting, whose theme is "prevention of abuse of minors and vulnerable adults", comes as the 1.3 billion-member Church still struggles to enact a concerted, coordinated and global effort to tackle a crisis that is now more than two decades old.
Lombardi, 71, said bishops from countries including the United States, which have developed protocols for preventing abuse and investigating accusations against individual members of the clergy, would share experiences and knowledge with those from developing countries, including those whose cultures make it harder to discuss abuse.
The Church has repeatedly come under fire for its handling of the sexual abuse crisis, which exposed how predator priests were moved from parish to parish instead of being defrocked or turned over to civilian authorities around the world.
Most of the crimes took place decades ago.
The pope called the meeting in September at the suggestion of his closest advisers, and last month he told reporters it was necessary because some bishops still did not know fully the procedures to put in place to protect the young and how to administer cases of abuse.
Francis said it would be a "catechesis," or a teaching session, a pronouncement that stunned victims of abuse and their advocates.
Some experts have questioned why it has taken so long to get to this point.
"The fact that this still exists in 2019, that there is still awareness-raising that has to be done (among bishops) is a measure of what a low priority this has truly been for the Vatican," said Anne Barrett-Doyle of the US-based abuse tracking group bishopaccountability.org.
"I hope he has the candour to admit that it's absolutely disgraceful that that's where we are today," said Barrett-Doyle, speaking in St. Peter's Square.
On Saturday the Vatican sent what some saw as a warning that it would get tough with bishops who have either committed abuse or covered it up.
It expelled former US Cardinal Theodore McCarrick from the Roman Catholic priesthood after he was found guilty of sexual crimes against minors and adults.
While many priests have been expelled for sexual abuse, few bishops have met the same fate, and McCarrick was the first former cardinal to be thrown out.
Archbishop Charles Scicluna, the Vatican's top sexual crimes investigator, told Reuters that McCarrick's dismissal was a "very important signal" to the Catholic hierarchy that no one is above the law.
While victims of sexual abuse and their advocates welcomed the expulsion, many were sceptical.
"I worry that this (McCarrick's expulsion) is not going to be anything more than the equivalent of the pope tossing a bone to placate his critics, placate the survivors," said Phil Saviano, who was molested by a priest in Massachusetts when he was 12 years old and whose story was told in the 2015 Oscar-winning film Spotlight.