CARTAGENA, Colombia (AP) — More than 220,000 deaths, 8 million homeless and countless human rights violations: These are the tragic toll of South America's oldest armed conflict, which begins to wind down with the signing Monday of a historic agreement between Colombia's government and the country's largest rebel movement to end a half-century of hostilities.

Underlining the significance of the deal, President Juan Manuel Santos and the top commander of the Revolutionary Armed Forces of Colombia, or FARC, a rebel fighter known by the alias Timochenko, were to sign the accord in the colonial city of Cartagena. Fifteen Latin American presidents as well as U.N. Secretary-General Ban Ki-moon and U.S. Secretary of State John Kerry were on hand to witness the signing.

In a ceremony charged with symbolism befitting an historic moment that generations of Colombians thought they would never see, the more than 2,500 guests were asked to wear white as a sign of peace and Santos was to sign the 297-page accord with a pen made from a recycled shell used in combat.

Earlier Monday, Santos and the foreign dignitaries attended a Mass celebrated by Cardinal Pietro Parolin, the Vatican's secretary of state, at a baroque church named for St. Peter Claver, a 17th-century Jesuit priest revered as the "slave of slaves" for his role aiding thousands of African slaves brought to the New World as chattel.

In a stirring homily, Pope Francis' envoy praised Colombians for overcoming the pain of the bloody conflict to find common ground with the rebels.

"All of us here today are conscious of the fact we're at the end of a negotiation, but also the beginning of a still open process of change that requires the contribution and respect of all Colombians," the cardinal said.

Across the country Colombians marked the occasion with a host of activities, from peace concerts by top-name artists to a street party in the capital, Bogota, where the signing ceremony was to be broadcast live on a giant screen. It was also celebrated by hundreds of guerrillas gathered in a remote region of southern Colombia where last week top commanders ratified the accord in what they said would be their last conference as a guerrilla army.

The signing won't close the deal, however. Colombians will be given the final say on endorsing or rejecting the accord in an Oct. 2 referendum. Opinion polls point to an almost-certain victory for the "yes" vote, but some analysts warn that a closer-than-expected finish or low voter turnout could bode poorly for the tough task the country faces in implementing the ambitious accord.

Among the biggest challenges will be judging the war crimes of guerrillas as well as state actors. Under terms of the accord, rebels who lay down their weapons and confess their abuses will be spared jail time and be allowed to provide reparations to their victims by carrying out development work in areas hard hit by the conflict.

That has angered some victims and conservative opponents of Santos, a few hundred of whom took to the streets Monday to protest what they consider the government's excessive leniency toward guerrilla leaders responsible for scores of atrocities in a conflict fueled by the country's cocaine trade.

To shouts of "Santos is a coward!" former President Alvaro Uribe, the architect of the decade-long, U.S.-backed military offensive that forced the FARC to the negotiating table, said the peace deal puts Colombia on the path to becoming a leftist dictatorship in the mold of Cuba or Venezuela — two countries that along with Norway played a vital role sponsoring the four-year-long talks.

"The democratic world would never allow bin Laden or those belonging to ISIS to become president, so why does Colombia have to allow the election of the terrorists who've kidnapped 11,700 children or raped 6,800 women?" he told protesters gathered in a working-class neighborhood on the outskirts of Cartagena.

The stiff domestic opposition contrasts with widespread acclaim abroad for the accord — a rare example in a war-torn world of what can be achieved through dialogue. On Monday, European Union foreign policy coordinator Federica Mogherini said that with the signing of the peace agreement, the EU would suspend the FARC from its list of terrorist organizations.

Asked whether the U.S. would follow suit, Kerry was less willing to commit but expressed a possible openness to similar action.

"We clearly are ready to review and make judgments as the facts come in," he told reporters. "We don't want to leave people on the list if they don't belong."

The FARC was established in 1964 by self-defense groups and communist activists who joined forces to resist a government military onslaught. Reflecting that history, the final accord commits the government to addressing unequal land distribution that has been at the heart of Colombia's conflict.

But as the war dragged on, and insurgencies elsewhere in Latin America were defeated, the FARC slipped deeper and deeper into Colombia's lucrative cocaine trade — to the point that President George W. Bush's administration in 2006 called it the world's biggest drug cartel.

As part of the peace process, the FARC has sworn off narcotics trafficking and agreed to work with the government to provide alternative development in areas where coca growing has flourished.

Only if the accord passes the referendum will the FARC's roughly 7,000 fighters begin moving to 28 designated zones where, over the next six months, they are to turn over their weapons to U.N.-sponsored observers.

Negotiations, which had been expected to take a few months, stretched over more than four years and had to overcome a number of crises, from the military's killing of the guerrilla group's then top commander, known as Alfonso Cano, shortly after he authorized a secret back channel with the government, to the rebels' capture of an army general who until a few months ago would have been a trophy prisoner.

"What's good about the fact that it lasted four years is that it was a very thorough process," Norwegian Foreign Minister Borge Brende told The Associated Press in an interview before Monday's signing. Norway and Cuba were co-sponsors of the negotiations that began in Oslo in 2012 and then shifted to Havana.

"The mindset of everyone has changed," Brende said. "I feel very genuinely that President Santos and Commander Timochenko want this to work and not go into the blame game."

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Associated Press writer Vivian Salama contributed to this report from Cartagena.

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Joshua Goodman is on Twitter: https://twitter.com/apjoshgoodman . His work can be found at http://bigstory.ap.org/journalist/joshua-goodman .