The Pacific nation's mountainous interior was struck by a 7.5-magnitude tremor on February 26, triggering landslides that blocked roads, caused power outages and cut off villages.
Communities have also been rattled by strong aftershocks, sparking fears among disenchanted and suspicious residents that the shaking was somehow caused by oil and gas operations in the area.
"Tragically, the Highlands earthquake has already claimed the lives of an estimated more than 100 Papua New Guineans, with many more still missing and thousands of people injured," O'Neill said.
"There will be no quick fix, the damage from this disaster will take months and years to be repaired," he said.
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"The social damage to our communities is large, and this earthquake will be the source of sadness and sorrow for generations to come," the prime minister added, describing the plight of one woman who lost six relatives including children.
"This is a story of tragedy and loss that is repeated in village after village throughout the disaster area."
Traumatised villagers are suspicious of the plant's operators and fearful they might have been using hydraulic fracturing, or fracking, and destabilised the rock structure underneath, the Post-Courier reported this week.
Hydraulic fracturing involves pumping large quantities of water and chemicals at high pressure deep into the Earth to fracture rock to stimulate the flow of natural gas or oil.
"I don't want the project to resume its operation until the company is cleared of suspicion of any responsibility," Hela province's governor Philip Undialu told the newspaper.
He told the Post-Courier that he went to the Hela capital of Tari on Wednesday and "they wanted an independent review and report on what is happening".
Canberra had no immediate comment.
ExxonMobil said Monday it expected its project to be offline for up to eight weeks to repair the quake-hit facilities.
PNG's growth is heavily dependent on its natural resources, and O'Neill has said the shutdown of the plant would have a "huge impact on the economy".
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