Scientists looked at tissue samples from patients
HPV infection was found to be a much stronger risk factor than tobacco or alcohol use, the Johns Hopkins University study of 300 people found.
The New England Journal of Medicine study said the risk was almost nine times higher for people who reported oral sex with more than six partners.
But experts said a larger study was needed to confirm the findings.
HPV infection is the cause of the majority of cervical cancers, and 80% of sexually active women can expect to have an HPV infection at some point in their lives.
The Johns Hopkins study took blood and saliva from 100 men and women newly diagnosed with oropharyngeal cancer which affects the throat, tonsils and back of the tongue.
They also asked questions about sex practices and other risk factors for the disease, such as family history.
Those who had evidence of prior oral HPV infection had a 32-fold increased risk of throat cancer.
HPV16 - one of the most common cancer-causing strains of the virus - was present in the tumours of 72% of cancer patients in the study.
There was no added risk for people infected with HPV who also smoked and drank alcohol, suggesting the virus itself is driving the risk of the cancer.
Oral sex was said to be the main mode of transmission of HPV but the researchers said mouth-to-mouth transmission, for example through kissing, could not be ruled out.
Most HPV infections clear with little or no symptoms but a small percentage of people who acquired high-risk strains may develop a cancer, the researchers added.
Study author Dr Gypsyamber D'Souza said: "It is important for health care providers to know that people without the traditional risk factors of tobacco and alcohol use can nevertheless be at risk of oropharyngeal cancer."
Co-researcher Dr Maura Gillison said previous research by the team had suggested there was a strong link.
But she added: "People should be reassured that oropharyngeal cancer is relatively uncommon and the overwhelming majority of people with an oral HPV infection probably will not get throat cancer."
A vaccine which protects against cervical cancer caused by HPV strains 6, 11, 16 and 18, and also against genital warts is available and the researchers said the study provided a rationale for vaccinating both girls and boys.
But whether the vaccine would protect against oral HPV infection is not yet known.
Dr Julie Sharp, science information officer at Cancer Research UK, said: "There is conflicting evidence about the role of HPV, and this rare type of mouth cancer.
"As this was a small study, further research is needed to confirm these observations."
"We know that after age, the main causes of mouth cancer are smoking or chewing tobacco or betel nut, and drinking too much alcohol."